Entrez-PubMed    

            EntrezPubMedNucleotideProteinGenomeStructurePMCJournalsBooks

             Search PubMed Protein Nucleotide Structure Genome Books 3D 
              Domains Domains Gene GEO GEO DataSets Journals MeSH NCBI Web Site 
              OMIM PMC PopSet SNP Taxonomy UniGene UniSTS  for     

              LimitsPreview/IndexHistoryClipboardDetails   


            About Entrez



      Text Version

      Entrez PubMed 
      Overview
      Help | FAQ
      Tutorial
      New/Noteworthy
      E-Utilities

      PubMed Services
      Journals Database
      MeSH Database
      Single Citation Matcher
      Batch Citation Matcher
      Clinical Queries
      LinkOut
      Cubby

      Related Resources
      Order Documents
      NLM Gateway
      TOXNET
      Consumer Health
      Clinical Alerts
      ClinicalTrials.gov
      PubMed Central

      Privacy Policy
       

              Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut 
              Related Articles Cited in Books Domain Links 3D Domain Links GEO 
              DataSet Links Gene Links Genome Links GEO Links Nucleotide Links 
              OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP 
              Links Structure Links UniSTS Links  Show: 5 10 20 50 100 200 500 
              Sort Author Journal Pub Date Text File Clipboard E-mail Order 
                  Items 1-118 of 118One page.


              1: Nippon Rinsho. 2003 Jun;61(6):1010-4. Related Articles, Links 


        [Disseminated intravascular coagulation]

        [Article in Japanese]

        Iba T, Kidokoro A.

        Department of Surgery, Juntendo University, Urayasu Hospital.

        Disseminated intravascular coagulation (DIC) is an acquired syndrome 
        characterized by systemic formation of microthrombi and fibrin 
        deposition in the vasculature. Cancer is one of the leading cause of 
        DIC, which often complicates bleeding tendency and organ dysfunction. 
        Even though DIC therapy is expectant, it is still important, since the 
        bleeding tendency limits the quality of patients' life remarkably. 
        Heparin, low molecular weight heparin, danaparoid, protease inhibitors 
        for coagulation factors and antithrombin III are the choices for DIC. 
        However, since the selection of the drugs is different depending on the 
        basal disease, it is important to understand the pathophysiology of the 
        individual situation. In general, protease inhibitors is recommended for 
        'fibrinolysis dominant DIC' like DIC associated with leukemia and 
        terminal stage solid cancer, in contrast, danaparoid and antithrombin 
        III are the first choice for 'coagulation dominant DIC' like sepsis. 
        Supplement of concentrated platelets and fresh frozen should be limited 
        for the patients whose primary disease can be controlled.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 12806952 [PubMed - indexed for MEDLINE] 




              2: Br J Sports Med. 2003;37(5):433-5. Related Articles, Links 

          
        Effects of strenuous exercise on haemostasis.

        Smith JE.

        Academic Department of Sports Medicine, Royal London Hospital (Mile 
        End), Bancroft Road, London E1, UK. jason.smith75@virgin.net

        OBJECTIVES: To review the effects of exercise on haemostasis and examine 
        the possible clinical sequelae of these changes. METHODS: The search 
        strategy included articles from 1966 to August 2002 using Medline and 
        SportDiscus databases, and cross referencing the bibliographies of 
        relevant papers. RESULTS: Exercise results in activation of both the 
        coagulation and fibrinolytic cascades, as shown by a reduction in whole 
        blood clotting time and activated partial thromboplastin time, an 
        increase in the activity of several components of the cascades, and an 
        increase in fibrin degradation products. In vitro tests suggest that 
        coagulation remains activated after fibrinolysis has returned to 
        baseline levels. CONCLUSIONS: Both the coagulation and fibrinolytic 
        cascades are stimulated by strenuous exercise, but the temporal relation 
        between the two and its clinical significance remains to be clarified. 
        Doctors and athletes should be aware of the haemostatic changes induced 
        by exercise, and further work is needed to clarify the possible role of 
        these changes in sudden cardiac death.

        PMID: 14514536 [PubMed - in process] 




              3: Thromb Res. 2002 Oct 31;107 Suppl 1:S9-17. Related Articles, 
              Links 

          
        Fresh frozen plasma in patients with disseminated intravascular 
        coagulation or in patients with liver diseases.

        Mueller MM, Bomke B, Seifried E.

        Red Cross Blood Donor Service, Frankfurt am Main, Germany. 
        mmueller@bsdhessen.de

        Disseminated intravascular coagulation (DIC) and liver diseases are 
        complex clinical conditions. Both disorders frequently disturb the 
        finely tuned coagulation and fibrinolysis equilibrium. In DIC, a wide 
        range of underlying disorders can induce a systemic activation of the 
        coagulation system with generation of soluble fibrin, possible 
        deposition of platelet-rich fibrin clots in the microvasculature and 
        subsequent micro- or macroembolism, impaired organ perfusion and organ 
        failure. Such coagulation activation depletes platelets, coagulation 
        factors, and inhibitors and clinically can result in severe, sometimes 
        untreatable bleeding, especially when bone marrow or liver function is 
        diminished or invasive procedures are performed. In addition, a 
        secondary counterbalancing activation of the fibrinolytic system to 
        dissolve microcirculatory clots adds to the bleeding tendency. In 
        conjunction with other options based on prompt and rigorous treatment of 
        the underlying cause of DIC, fresh frozen plasma plays an important role 
        in therapeutic management when overt bleeding is present or anticipated 
        in DIC patients with disturbed coagulation or when an invasive procedure 
        is being planned.In liver disease, factor and inhibitor synthesis in 
        both the coagulation and fibrinolytic system is impaired, both 
        quantitatively and qualitatively. This destabilizes the balance between 
        the two systems. In addition, the clearance of activated coagulation 
        factors and fibrin(ogen) degradation products (FDP) from the systemic 
        circulation is impaired. In patients with liver diseases and acute or 
        imminent bleeding, or before invasive procedures, fresh frozen plasma 
        (FFP) offers advantages over clotting factor concentrates. However, 
        hypervolemia following the required doses of FFP might pose a problem in 
        some liver disease patients.The complex pathophysiology both in DIC and 
        in liver disease requires early diagnosis and adequate management 
        including plasma and platelet substitution after treatment of the 
        underlying disease. Due to the heterogeneity of DIC and liver disease, 
        prospective randomized trials are difficult to perform. Therefore, 
        treatment recommendations are mostly empirical and less evidence-based. 
        Therapy must be accompanied by close and repeated clinical and 
        laboratory monitoring.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 12379287 [PubMed - indexed for MEDLINE] 




              4: World J Surg. 2002 Jul;26(7):767-71. Epub 2002 Apr 30.Related 
              Articles, Links 

          
        Plasmin/plasminogen system in colorectal cancer.

        Berger DH.

        Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 
        One Baylor Plaza, Houston, Texas 77030, USA.

        Pericellular proteolysis plays a crucial role in tumor cell invasion. 
        The controlled degradation of the extracellular matrix by tumor 
        cell-associated proteases allows tumor cells to invade surrounding 
        tissues and gain access to the circulation. One of the main protease 
        systems involved in tumor cell invasion and metastasis is the 
        plasminogen/plasmin system (PPS). The components of the PPS include the 
        urokinase plasminogen activator (uPA), its cell surface receptor 
        urokinase plasminogen activator receptor (uPAR), and its naturally 
        occurring inhibitors, plasminogen activator inhibitors 1 and 2 (PAI-1 
        and PAI-2). Increases in tumor and serum levels of uPA, uPAR, and PAI-1 
        are associated with a worse prognosis in patients with colon cancer. Use 
        of these proteins as either tumor or serum markers may allow more 
        accurate determination of the prognosis in colon cancer patients. 
        Furthermore, these proteins appear to be attractive as targets for the 
        biologic therapy of colon cancer.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11965442 [PubMed - indexed for MEDLINE] 




              5: Essays Biochem. 2002;38:95-111. Related Articles, Links 


        Proteases in blood clotting.

        Walsh PN, Ahmad SS.

        Sol Sherry Thrombosis Research Center, Temple University School of 
        Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA. 
        pnw@astro.temple.edu

        The serine proteases, cofactors and cell-receptor molecules that 
        comprise the haemostatic mechanism are highly conserved modular proteins 
        that have evolved to participate in biochemical reactions in blood 
        coagulation, anticoagulation and fibrinolysis. Blood coagulation is 
        initiated by exposure of tissue factor, which forms a complex with 
        factor VIIa and factor X, which results in the generation of small 
        quantities of thrombin and is rapidly shutdown by the tissue factor 
        pathway inhibitor. The generation of these small quantities of thrombin 
        then activates factor XI, resulting in a sequence of events that lead to 
        the activation of factor IX, factor X and prothrombin. Sufficient 
        thrombin is generated to effect normal haemostasis by converting 
        fibrinogen into fibrin. The anticoagulant pathways that regulate blood 
        coagulation include the protein C anticoagulant mechanism, the serine 
        protease inhibitors in plasma, and the Kunitz-like inhibitors, tissue 
        factor pathway inhibitor and protease nexin 2. Finally, the fibrinolytic 
        mechanism that comprises the activation of plasminogen into plasmin 
        prevents excessive fibrin accumulation by promoting local dissolution of 
        thrombi and promoting wound healing by reestablishment of blood flow.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 12463164 [PubMed - indexed for MEDLINE] 




              6: J Crit Care. 2001 Dec;16(4):167-77. Related Articles, Links 

          
        Pathogenesis and treatment of disseminated intravascular coagulation in 
        the septic patient.

        Levi M.

        Department of Vascular Medicine, Academic Medical Center, University of 
        Amsterdam, Amsterdam, The Netherlands.

        The incidence of sepsis and complications stemming from septicemia has 
        remained constant in recent years despite improved levels of monitoring 
        and care. Disseminated intravascular coagulation (DIC), a syndrome that 
        occurs frequently in septic patients, is associated with increased 
        mortality. Organ dysfunction is also a common sequela that is strongly 
        correlated with DIC. Cytokines released early in the course of sepsis 
        stimulate a procoagulant state that causes development of intravascular 
        fibrin deposition. In a later stage of DIC, bleeding may occur in 
        parallel because of consumption of clotting factors and inhibitors. 
        Therapeutic strategies to attenuate or reverse these conditions have 
        focused on multiple stages of the molecular cascade of events, including 
        preventing cytokine induction, inhibiting coagulation processes, and 
        promoting fibrinolysis. Recent clinical trials have supported the use of 
        antithrombin and activated protein C supplementation in DIC associated 
        with severe sepsis. Studies of other novel therapeutic avenues are still 
        ongoing. Future efforts may be directed at combining 2 or more agents to 
        achieve prompt and successful reversal of DIC. Copyright 2002 by W.B. 
        Saunders Company

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11815902 [PubMed - indexed for MEDLINE] 




              7: Semin Thromb Hemost. 2001 Dec;27(6):633-8. Related Articles, 
              Links 

          
        Fibrinolysis in disseminated intravascular coagulation.

        Hack CE.

        Central Laboratory of the Netherlands Red Cross Blood Transfusion 
        Service, Laboratory for Experimental and Clinical Immunology, University 
        of Amsterdam, The Netherlands. Hack@CLB.nl

        Studies in experimental models for sepsis, the most common cause of 
        disseminated intravascular coagulation (DIC), have put forward the 
        concept of a procoagulant state that is characterized by thrombin 
        generation exceeding that of plasmin. Convincing evidence indicates that 
        this imbalance between coagulation and fibrinolysis is due to increased 
        levels of plasminogen activator inhibitor type 1 (PAI-1). Levels of this 
        fibrinolysis inhibitor indeed correlate with outcome and severity of 
        multiple organ failure in patients with sepsis, as well as in patients 
        with DIC from other causes. Hence we suggest that PAI-1 constitutes an 
        important target for therapy in patients with DIC.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11740686 [PubMed - indexed for MEDLINE] 




              8: Clin Appl Thromb Hemost. 2001 Jul;7(3):229-33. Related 
              Articles, Links 


        Plasma levels of total plasminogen activator inhibitor-I (PAI-I) and 
        tPA/PAI-1 complex in patients with disseminated intravascular 
        coagulation and thrombotic thrombocytopenic purpura.

        Watanabe R, Wada H, Miura Y, Murata Y, Watanabe Y, Sakakura M, Okugawa 
        Y, Nakasaki T, Mori Y, Nishikawa M, Gabazza EC, Shiku H, Nobori T.

        DepartmentSecond Department of Internal Medicine, Mie University School 
        of Medicine, Tsu-city, Japan.

        In this study, we examined changes in the plasma levels of total 
        plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen 
        activator (tPA)/PAI-I complex in patients with disseminated 
        intravascular coagulation (DIC) and in those with thrombotic 
        thrombocytopenic purpura (TTP) to investigate the fibrinolytic function 
        and its relation to organ failure. The plasma levels of total PAI-1 and 
        tPA/PAI-I complex were significantly higher in patients with DIC, 
        pre-DIC, and TTP than in those with non-DIC. The plasma levels of 
        thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex 
        (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex 
        were significantly higher in patients with organ failure than in those 
        without organ failure. The plasma levels of total PAI-I and tPA/PAI-I 
        complex were markedly increased in patients with acute leukemia. The 
        plasma levels of total PAI-I, but not those of tPA/PAI-I complex, were 
        significantly increased in patients with sepsis or with solid cancer. In 
        all cases, total PAI-I or tPA/PAI-I complex was not significantly 
        correlated with any hemostatic marker. Measurement of total PAI-I and 
        tPA/PAI-I complex may be useful in the diagnosis of DIC.

        PMID: 11441985 [PubMed - indexed for MEDLINE] 




              9: Crit Care Med. 2001 Jun;29(6):1164-8. Related Articles, Links 

          
        An enhanced fibrinolysis prevents the development of multiple organ 
        failure in disseminated intravascular coagulation in spite of much 
        activation of blood coagulation.

        Asakura H, Ontachi Y, Mizutani T, Kato M, Saito M, Kumabashiri I, 
        Morishita E, Yamazaki M, Aoshima K, Nakao S.

        Department of Internal Medicine (III), Kanazawa University School of 
        Medicine, Takaramachi 13-1, Kanazawa 920-8641, Japan.

        OBJECTIVES: To investigate the relationship between fibrinolytic 
        enhancement and the development of multiple organ failure (MOF) in 
        disseminated intravascular coagulation (DIC). To detect the useful 
        prognostic index for outcome in DIC. DESIGN: Case-control study. 
        SETTING: A department of internal medicine in a university hospital, a 
        clinical division for diagnosis and treatment, mainly of respiratory 
        diseases, hematologic diseases, DIC, and other diseases requiring 
        critical care medicine. PATIENTS: A total of 69 DIC patients, 31 with 
        MOF. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The DIC patients 
        with MOF had more elevated levels of tissue plasminogen activator 
        antigen (t-PA) and plasminogen activator inhibitor antigen (PAI), and 
        more depressed levels of plasmin-alpha2 plasmin inhibitor complex (PIC) 
        and fibrin/fibrinogen degradation products than those without MOF, 
        although no significant difference in thrombin-antithrombin complex 
        (TAT) levels was observed. A fibrinolytic enhancement (shown by PIC) was 
        parallel to an activation of blood coagulation (shown by TAT) in DIC 
        patients without MOF, although no such fibrinolytic enhancement was 
        provoked even by much activation of blood coagulation in DIC patients 
        with MOF. Whereas all the patients without MOF were restored from DIC, 
        14 of 31 patients with MOF were unable to be restored from DIC and died. 
        A significant increase in plasma levels of t-PA and PAI under the 
        condition of sustained hemostatic activation was observed in the 
        patients who died. CONCLUSION: Enhanced fibrinolysis was considered to 
        be the important defense mechanism in preventing the development of MOF 
        in DIC. The increases in plasma levels of t-PA and PAI were poor 
        prognostic markers in DIC. Further careful study may be useful to 
        clarify whether the fibrinolytic therapy is beneficial in clinical DIC 
        patients with MOF.

        PMID: 11395595 [PubMed - indexed for MEDLINE] 




              10: Acta Haematol. 2001;106(1-2):18-24. Related Articles, Links 

          
        Pathogenetic mechanisms of thrombosis in malignancy.

        Donati MB, Falanga A.

        Department of Vascular Medicine and Pharmacology, Istituto di Ricerche 
        Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Via Nazionale, 
        I-66030 Santa Maria Imbaro, Italy. donati@cmns.mnegri.it

        The interactions between components of the hemostatic system and cancer 
        cells are multifaceted. Strong clinical evidence is accumulating on the 
        prothrombotic tendency of cancer patients, which is enhanced by 
        anticancer therapy, such as surgery and chemotherapy. The mechanisms of 
        thrombus promotion in malignancy include some general responses of the 
        host to the tumor (acute phase, inflammation, angiogenesis) and specific 
        interactions of tumor cells with the clotting/fibrinolysis systems and 
        with blood (leukocytes, platelets) or vascular cells. It is at present 
        difficult to rank the relative weight of these multiple interactions on 
        the basis of the well-recognized clinical evidence of enhanced 
        thrombotic episodes in tumor patients. In any case, the mechanisms 
        explored so far offer a sound experimental basis for 
        prevention/treatment of thrombosis in tumor patients and leave open the 
        possibility that some antithrombotic strategies may also affect the 
        processes of tumor growth and dissemination. Copyright 2001 S. Karger 
        AG, Basel

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11549773 [PubMed - indexed for MEDLINE] 




              11: Acta Haematol. 2001;106(1-2):25-32. Related Articles, Links 

          
        Update on tumor cell procoagulant factors.

        Gale AJ, Gordon SG.

        Department of Molecular and Experimental Medicine, The Scripps Research 
        Institute, La Jolla, CA., USA.

        Tumor cells produce tissue factor, cancer procoagulant, plasminogen 
        activators and other factors that interact with the coagulation system, 
        the fibrinolytic system and vascular or blood cells such that they can 
        upset the normal homeostasis and balance between activation and 
        inhibition of the coagulation and fibrinolytic systems. These activities 
        play a role in tumor cell growth and metastasis, vascular wall function, 
        and hemostasis. Proteases and their inhibitors are intimately involved 
        in all aspects of the hemostatic, cell proliferation and cellular 
        signalling systems. This review provides a brief examination of recent 
        observations in this complex interaction of cellular and hemostatic 
        factors. Copyright 2001 S. Karger AG, Basel

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11549774 [PubMed - indexed for MEDLINE] 




              12: Acta Haematol. 2001;106(1-2):33-42. Related Articles, Links 

          
        The thrombophilic state in cancer patients.

        Gouin-Thibault I, Achkar A, Samama MM.

        Laboratoire d'Hematologie, Groupe hospitalier Charles Foix-Jean Rostand, 
        Ivry-sur-Seine, France.

        Thrombosis and disseminated intravascular coagulation are common 
        complications of cancer. Specific conditions associated with cancer such 
        as stasis due to immobilization or blood flow obstruction, surgery, 
        infections, endothelium damage due to chemotherapeutic agents and 
        abnormalities of blood coagulation contribute to the hypercoagulable and 
        thrombophilic state of cancer patients. This procoagulant state in 
        cancer arises mostly from the capacity of tumor cells to express and 
        release procoagulant activities (cancer procoagulant and tissue factor). 
        Decreased levels of inhibitors of coagulation, impaired fibrinolysis, 
        the presence of antiphospholipid antibodies and an acquired activated 
        protein C resistance contribute to the hypercoagulable state. The 
        activation of coagulation is also implicated in tumor proliferation 
        through interactions of coagulation with inflammation and increased 
        tissue factor pathway inhibitor. Laboratory diagnosis of the 
        thrombophilic state include (1) elevation of clotting factors, 
        fibrinogen/fibrin degradation products, hyperfibrinogenemia and 
        thrombocytosis and (2) elevation of specific markers of activation of 
        coagulation: fibrinopeptide A, fragment 1 + 2, thrombin-antithrombin 
        complexes and D-dimers. However, none of the tests has any predictive 
        value for the occurrence of thrombotic events in one individual patient. 
        In patients with venous thromboembolism a noninvasive screening for 
        occult cancer is able to detect a relatively high incidence of hidden 
        cancer and the search for thrombophilia seems important in patients 
        without known cancer. Copyright 2001 S. Karger AG, Basel

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11549775 [PubMed - indexed for MEDLINE] 




              13: Haemostasis. 2001;31 Suppl 1:1-4. Related Articles, Links 


        Tumor cell prothrombotic properties.

        Falanga A.

        Dept. Hematology-Oncology, Ospedali Riuniti, Bergamo, Italy. 
        annafalanga@yahoo.com

        Thrombin generation and fibrin formation are constantly determined in 
        patients with malignancy, who are at increased risk of thromboembolic 
        complications. Most importantly, fibrin formation is also involved in 
        the processes of tumor spread and metastasis. Activation of blood 
        coagulation in cancer is a complex phenomenon, involving many different 
        pathways of the hemostatic system and numerous interactions of the tumor 
        cell with other blood cells, including platelet, monocyte and 
        endothelial cell. Tumor cells possess the capacity to interact with all 
        parts of the hemostatic system. They can directly activate the 
        coagulation cascade by producing their own procoagulant factors or they 
        can stimulate the prothrombotic properties of other blood cell 
        components. All of the mechanisms are not entirely understood, however 
        research studies in the last ten years have greatly improved our 
        knowledge of tumor-promoted pro-thrombotic functions.

        Publication Types: 
          Lectures

        PMID: 11990464 [PubMed - indexed for MEDLINE] 




              14: Am J Hematol. 2000 Nov;65(3):215-22. Related Articles, Links 

          
        Heterogeneity in the incidence and clinical manifestations of 
        disseminated intravascular coagulation: a study of 204 cases.

        Okajima K, Sakamoto Y, Uchiba M.

        Department of Laboratory Medicine, Kumamoto University School of 
        Medicine, Japan. whynot@kaiju.medic.kumamoto-u.ac.jp

        The incidence and clinical manifestations of disseminated intravascular 
        coagulation (DIC) were examined in patients with a range of underlying 
        disorders. Out of 1,882 patients suspected as having DIC, 204 cases were 
        diagnosed as suffering from DIC and included in this study. The 
        underlying disorders experienced by the patients were solid tumors 
        (33.8%), hematologic malignancies (12.7%), aortic aneurysm (10.8%), 
        infections (6.4%), post-operative complications (4.4%), liver disease 
        (2.9%), obstetric disorders (2.5%), and miscellaneous diseases (26.5%). 
        The incidence of DIC was 10.8% out of all patients suspected of having 
        DIC, and the etiologies were 10.9% in solid tumors, 10.1% in 
        hematological malignancies, 20.4% in aortic aneurysm, 12.7% in 
        infections, 15.5% in post-operative complications, 15.8% in liver 
        disease, 3.7% in obstetric disorders, and 9.8% in miscellaneous 
        diseases. The clinical manifestations of DIC patients were varying 
        dependent on their etiologies. Most DIC patients with aortic aneurysm 
        (95.5%) and post-operative complications (88.9%) did not reveal any 
        clinical manifestations. Although all of the patients with obstetric 
        disorders had bleeding, only 20.0% of the patients had organ failure. In 
        contrast, although only 15.4% of the patients with infections had 
        bleeding, 76.9% of these patients had organ failure. Bleeding was 
        observed in 31.9-50.0% of DIC patients with liver disease, hematologic 
        malignancies, and solid tumors. Organ failure was observed in 21.7-33.3% 
        of DIC patients with liver disease, hematological malignancies, and 
        solid tumors. Analysis by measurement of plasma levels of antiplasmin 
        and plasmin-antiplasmin complex suggested that excessive fibrinolysis 
        might contribute to the development of bleeding in these DIC patients. 
        Differences in plasma levels of thrombin-antithrombin complex and 
        cross-linked fibrin degradation products could not account for the 
        differences in the incidence of organ failure in the patients. These 
        findings suggest that the clinical manifestation of DIC varies and might 
        not only be a reflection of microthrombus formation but also a 
        reflection of the other underlying pathomechanisms.

        PMID: 11074538 [PubMed - indexed for MEDLINE] 




              15: Recenti Prog Med. 2000 Oct;91(10):532-7. Related Articles, 
              Links 


        [Blood coagulation changes and neoplastic pathology]

        [Article in Italian]

        Corsi MP, De Martinis M, Di Leonardo G, Loreto MF, Modesti M, Quaglino 
D.

        Dipartimento di Medicina Interna e Sanita Pubblica, Universita, 
L'Aquila.

        Cancer patients show an increased susceptibility to develop 
        thromboembolic diseases, suggesting that disorders of coagulation are 
        very common in this pathology. Tumor cells possess the capacity to 
        interact with the hemostatic system, activating the coagulation cascade 
        and stimulating the prothrombotic properties of other blood cell 
        components; the same events while inducing a hypercoagulable state, also 
        contribute to the processes of tumor growth, neoangiogenesis and 
        metastatic formation. Multiple risk factors associated with malignant 
        disease contribute to the hypercoagulability state: stasis induced by 
        prolonged bed rest, vascular invasion by the tumor and iatrogenic 
        complications including the use of central vein catheters and 
        chemotherapy. Several tests have been developed to assess the 
        hypercoagulable state, however their clinical significance still needs 
        to be defined, especially in terms of their predictive value for 
        thrombosis. Clinical manifestations vary from localized deep venous 
        thrombosis (DVT) or pulmonary embolism, more generally associated with 
        solid tumors, to disseminated intravascular coagulation, frequent in 
        hematologic malignancies and metastatic cancer. Diagnosis of idiopathic 
        DVT, in the absence of other risk factors, could indicate the presence 
        of occult cancer, but the usefulness of an extensive work-up to detect 
        malignancy in terms of cost to benefit ratio still has to be 
        demonstrated. Patients with cancer and thromboembolism must be treated 
        with anticoagulant therapy; a large number of studies have shown that 
        either low molecular weight heparins or standard unfractionated heparin 
        for the treatment of acute deep vein thrombosis in hospitalized patients 
        are equally safe and effective; however, the first treatment has been 
        reported to be associated with a lower mortality. After an episode of 
        thrombosis the patients should be protected by a long term course of 
        oral anticoagulation, remaining high the risk of recurrence for as long 
        as the cancer is active.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 11072743 [PubMed - indexed for MEDLINE] 




              16: Clin Chem Lab Med. 2000 Aug;38(8):679-92. Related Articles, 
              Links 


        Changes of the coagulation and fibrinolysis system in malignancy: their 
        possible impact on future diagnostic and therapeutic procedures.

        Korte W.

        Institute for Clinical Chemistry and Haematology, Kantonsspital, St. 
        Gallen, Switzerland. wolfgang.korte@gd-ikch.sg.ch

        The interaction between malignant cell growth and the coagulation and 
        fibrinolysis system has been a well known phenomenon for decades. During 
        recent years, this area of research has received new attention. 
        Experimental data suggest a role for the coagulation and fibrinolysis 
        system in tumor development, progression and metastasis. Also, clinical 
        research suggests that targeting the coagulation system or fibrinolysis 
        system might influence the course of malignant disease beneficially. 
        This paper reviews data on various hemostatic and fibrinolytic 
        parameters in malignancy; the possible use of such parameters as risk 
        markers in oncology patients; and possible targets of anti-neoplastic 
        therapies using anticoagulant and/or antifibrinolytic strategies. 
        Current evidence suggests that the tissue factor/factor VIIa pathway 
        mediates the most abundant procoagulant stimulus in malignancy via the 
        increase in thrombin generation. Tissue factor has been suggested to 
        mediate pro-metastatic properties via coagulation-dependent and 
        coagulation-independent pathways; tissue factor has also been implicated 
        in tumor neo-angiogenesis. However, so far no model has been validated 
        that would allow the use of tissue factor in its soluble or insoluble 
        form as a marker for risk stratification in tumor patients. On the other 
        hand, there is now good evidence that parts of the fibrinolytic system, 
        such as urokinase-type plasminogen activator and its receptor ("uPAR"), 
        can be used as strong predictors of outcome in several types of cancer, 
        specifically breast cancer. Observation of various treatment options in 
        patients with thromboembolic disease and cancer as well as attempts to 
        use anticoagulants and/or therapies modulating the fibrinolytic system 
        as anti-neoplastic treatment strategies have yielded exciting results. 
        These data indicate that anticoagulant therapy, and specifically low 
        molecular weight heparin therapy, is likely to have anti-neoplastic 
        effects; and that their use in addition to chemotherapy will probably 
        improve outcome of tumor treatment in certain types of cancer. However, 
        the body of clinical data is still relatively small and the question 
        whether or not we should routinely consider the coagulation and/or 
        fibrinolysis system as therapeutic targets in cancer patients is yet to 
        be answered.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 11071061 [PubMed - indexed for MEDLINE] 




              17: Eur J Cancer. 2000 Aug;36(13 Spec No):1695-705. Related 
              Articles, Links 

          
        No grip, no growth: the conceptual basis of excessive proteolysis in the 
        treatment of cancer.

        Reijerkerk A, Voest EE, Gebbink MF.

        Laboratory of Medical Oncology, Department of Internal Medicine, 
        University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, 
        The Netherlands.

        The formation of new bloodvessels, called angiogenesis, is critical for 
        a tumour to grow beyond a few mm(3) in size. A provisional matrix 
        promotes endothelial cell adhesion, migration, proliferation and 
        survival. Synthesis and degradation of this matrix closely resemble 
        processes that occur during coagulation and fibrinolysis. Degradation of 
        the matrix and fibrinolysis are tightly controlled and balanced by 
        stimulators and inhibitors of the plasminogen activation system. Here we 
        give an overview of these processes during tumour progression. We 
        postulate a novel way to inhibit angiogenesis by removal of the matrix 
        through specific and localised overstimulation of the plasminogen 
        activation system.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 10959055 [PubMed - indexed for MEDLINE] 




              18: Ned Tijdschr Geneeskd. 2000 Mar 4;144(10):470-5. Related 
              Articles, Links 


        [Disseminated intravascular coagulation]

        [Article in Dutch]

        Levi M, de Jonge E, ten Cate H.

        Academisch Medisch Centrum/Universiteit van Amsterdam, afd. Inwendige 
        Geneeskunde en afd. Intensive Care, Amsterdam.

        Disseminated intravascular coagulation is characterised by systemic 
        activation of blood coagulation, resulting in formation of intravascular 
        thrombi and impaired organ perfusion. Simultaneously, the ongoing 
        consumption of platelets and coagulation factors may lead to bleeding. 
        Disseminated intravascular coagulation is seen in septicaemic 
        infections, trauma, malignancies, obstetrical complications, vascular 
        diseases, toxic and immunological reactions. In summary, the systemic 
        deposition of fibrin is caused by enhanced thrombin generation, 
        simultaneous depression of physiological anticoagulant mechanisms and 
        diminished fibrin degradation due to inhibition of fibrinolysis. The 
        increased insight into the pathogenesis of disseminated intravascular 
        coagulation provides a solid basis for development of improved 
        management strategies for patients with this complication. Therapy may 
        include anticoagulants, platelet and plasma transfusion, concentrates of 
        coagulation inhibitors and antifibrinolytic agents.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 10726156 [PubMed - indexed for MEDLINE] 




              19: Cell Mol Life Sci. 2000 Jan 20;57(1):25-40. Related Articles, 
              Links 


        The plasminogen activation system in tumor growth, invasion, and 
        metastasis.

        Andreasen PA, Egelund R, Petersen HH.

        Department of Molecular and Structural Biology, Aarhus University, 
        Denmark. pa@mbio.aau.dk

        Generation of the serine proteinase plasmin from the extracellular 
        zymogen plasminogen can be catalyzed by either of two other serine 
        proteinases, the urokinase- and tissue-type plasminogen activators (uPA 
        and tPA). The plasminogen activation system also includes the serpins 
        PAI-1 and PAI-2, and the uPA receptor (uPAR). Many findings, gathered 
        over several decades, strongly suggest an important and causal role for 
        uPA-catalyzed plasmin generation in cancer cell invasion through the 
        extracellular matrix. Recent evidence suggests that the uPA system is 
        also involved in cancer cell-directed tissue remodeling. Moreover, the 
        system also supports cell migration and invasion by plasmin-independent 
        mechanisms, including multiple interactions between uPA, uPAR, PAI-1, 
        extracellular matrix proteins, integrins, endocytosis receptors, and 
        growth factors. These interactions seem to allow temporal and spatial 
        reorganizations of the system during cell migration and a selective 
        degradation of extracellular matrix proteins during invasion. The 
        increased knowledge about the plasminogen activation system may allow 
        utilization of its components as targets for anti-invasive therapy.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 10949579 [PubMed - indexed for MEDLINE] 




              20: Semin Thromb Hemost. 1999;25(2):183-97. Related Articles, 
              Links 


        The role of the plasminogen activation system in cancer.

        Carroll VA, Binder BR.

        Department of Vascular Biology and Thrombosis Research, University of 
        Vienna, Austria.

        Hemostatic disorders are frequently observed in patients with malignancy 
        with a significant proportion developing thrombotic and/or hemorrhagic 
        complications including disseminated intravascular coagulation (DIC), 
        deep venous thrombosis (DVT), and thrombocytopenia. Together, these 
        abnormalities are the second most common cause of mortality in cancer 
        patients, which has led many investigators to try to unravel the 
        pathogenesis of thromboembolic disease, in the eventuality that this 
        will lead to novel therapeutic treatments. The plasminogen activation 
        system is one pathway that has been consistently implicated in cancer. 
        Its relevance to cancer extends from being responsible for many of the 
        hemorrhagic episodes that occur in cancer patients to being fundamental 
        to many, if not all of the molecular mechanisms that define tumor 
        progression. Recent developments of clinical significance shall be 
        reviewed with respect to the role of the plasminogen activation system 
        in tumor growth and metastasis dissemination and in the thrombophilic 
        state in the cancer patient.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 10357086 [PubMed - indexed for MEDLINE] 




              21: Vestn Ross Akad Med Nauk. 1999;(8):58-61. Related Articles, 
              Links 


        [The clinical prospects for the study of the plasminogen activation 
        system in breast cancer]

        [Article in Russian]

        Gershtein ES, Kushlinskii NE.

        Urokinase-type plasminogen activator (UPA) which is a serine protease 
        may play a key role in the processes of tumor invasion and metastasis 
        since it converts plasminogen to plasmin and initiates a cascade of 
        proteolytic events that lead to the degradation of extracellular matrix. 
        Experiments have demonstrated that some other components, except UPA 
        itself, can be very important in this process, including UPA receptor 
        (UPAR) and UPA inhibitors PAI-1 and PAI-2. All these proteins are 
        present either in the tumor cells or in the tumor-infiltrating 
        macrophages and stromal elements, and by acting in concert, they provide 
        a feed-back-regulated mechanism of plasmin activation and amplification. 
        Clinical retrospective studies using predominantly ELISA techniques have 
        shown that the high levels of UPA, PAI-1 and UPAR in the tumor tissue 
        are associated with poor prognosis both for overall and for disease-free 
        survival of breast cancer patients, and the elevated level of PAI-2 may 
        be indicative of better survival. UPA and PAI-1 are now regarded as 
        rather potent independent predictors in breast cancer. Further clinical 
        prospects of investigations and application of the components of the 
        plasminogen activation system are discussed.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 10487126 [PubMed - indexed for MEDLINE] 




              22: Baillieres Clin Haematol. 1998 Sep;11(3):675-87. Related 
              Articles, Links 


        Venous thromboembolism and cancer.

        Kakkar AK, de Lorenzo F, Pineo GF, Williamson RC.

        Department of Surgery, Imperial College School of Medicine, Hammersmith 
        Hospital, London, UK.

        The association of thrombosis with malignant disease has been recognized 
        for well over 100 years. Evidence from experimental and clinical studies 
        indicates that the haemostatic system is involved in the growth, 
        invasion and metastasis of tumours. Laboratory parameters of haemostasis 
        are frequently deranged in patients with cancer and overt thrombosis is 
        common spontaneously where it may be the first sign of malignancy or 
        secondary to therapy. The mechanisms by which coagulation activation 
        facilitates the malignant process remain to be completely elucidated, 
        but it is clear that cells and proteins of the coagulation and 
        fibrinolytic systems are involved at many steps in the processes of 
        tumour growth and dissemination. The low-molecular-weight heparins with 
        their well-proven safety and efficacy profiles offer unique modalities 
        for the prevention and treatment of cancer-associated thrombosis. They 
        may also play a role in overall mortality reduction in patients with 
        malignant disease.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 10331099 [PubMed - indexed for MEDLINE] 




              23: Clin Exp Metastasis. 1998 Aug;16(6):513-28. Related Articles, 
              Links 


        Plasminogen activator system modulates invasive capacity and 
        proliferation in prostatic tumor cells.

        Festuccia C, Dolo V, Guerra F, Violini S, Muzi P, Pavan A, Bologna M.

        Department of Experimental Medicine, University of L'Aquila, Italy.

        The malignant phenotype of prostatic tumor cells correlates with the 
        expression of both uPA and its cell-membrane receptor (uPAR); however, 
        there is little information concerning the role of cell-bound uPA in 
        matrix degradation and invasion. Our results suggest that 
        cell-associated uPA plays a key role in regulating the amount of plasmin 
        present at the surface of prostatic carcinoma (PRCA) cells and show that 
        differential production of uPA corresponds with the capacity to bind and 
        activate plasminogen. In addition, we provide direct evidence that both 
        uPA secretion and the presence of uPA-uPAR complexes characterize the 
        invasive phenotype of PRCA cells and suggest the existence of several 
        pathways by which tumor cells acquire plasmin activity. LNCaP cells 
        (which do not produce uPA but express uPAR) may activate plasmin through 
        exogenous uPA. In vivo, the source of uPA may be infiltrating 
        macrophages and/or fibroblasts as observed in several other systems. 
        PAI-1 accumulation in the conditioned medium (CM) limits plasmin action 
        to the pericellular microenvironment. Our results indicate that MMP-9 
        and MMP-2 are also activated by plasmin generated by cell-bound but not 
        by soluble, extracellular uPA. Plasmin activation and triggering of the 
        proteolytic cascade involved in Matrigel invasion is blocked by 
        antibodies against uPA (especially by anti- A-chain of uPA which 
        interacts with uPAR) and by PA inhibitors such as p-aminobenzamidine 
        which may regulate levels of cell-bound uPA. uPA may also regulate 
        growth in PRCA cells. Indeed, antibodies against uPA A-chain (and also 
        p-aminobenzamidine treatment) interfere with the ATF domain and inhibit 
        cell growth in uPA-producing PC3 and DU145 prostate cancer cell lines, 
        whereas exogenous uPA (HMW-uPA with ATF) induces growth of LNCaP 
        prostate tumor cell line. These data support the hypothesis that in 
        prostatic cancer patients at risk of progression, uPA/plasmin blockade 
        may be of therapeutic value by blocking both growth of the primary tumor 
        and dissemination of metastatic cells.

        PMID: 9872599 [PubMed - indexed for MEDLINE] 




              24: Drugs. 1998 Jun;55(6):767-77. Related Articles, Links 


        Current drug treatment strategies for disseminated intravascular 
        coagulation.

        de Jonge E, Levi M, Stoutenbeek CP, van Deventer SJ.

        Department of Intensive Care, Academic Medical Center, University of 
        Amsterdam, The Netherlands. E.dejonge@amc.uva.nl

        Disseminated intravascular coagulation (DIC) can be caused by a variety 
        of diseases. Experimental models of DIC have provided substantial 
        insight into the pathogenesis of this disorder, which may ultimately 
        result in improved treatment. Disseminated coagulation is the result of 
        a complex imbalance of coagulation and fibrinolysis. Simultaneously 
        occurring tissue factor-dependent activation of coagulation, depression 
        of natural anticoagulant pathways and shutdown of endogenous 
        fibrinolysis all contribute to the clinical picture of widespread 
        thrombotic deposition in the microvasculature and subsequent multiple 
        organ failure. Cornerstone for the treatment of DIC is the optimal 
        management of the underlying disorder. At present, specific treatment of 
        the coagulation disorders themselves is not based on firm evidence from 
        controlled clinical trials. Plasma and platelet transfusion are used in 
        patients with bleeding or at risk for bleeding and low levels of 
        coagulation factors or thrombocytopenia. The role of heparin and low 
        molecular weight heparin is controversial, but their use may be 
        justified in patients with active DIC and clinical signs of extensive 
        fibrin deposition such as those with meningococcal sepsis. There is some 
        evidence to indicate that low molecular weight heparin is as effective 
        as unfractionated heparin but may be associated with a decreased 
        bleeding risk. Antithrombin III (AT III) replacement appears to be 
        effective in decreasing the signs of DIC if high doses are administered, 
        but effects on survival or other clinically significant parameters are 
        at best uncertain. If AT III supplementation is used, the dosage should 
        be selected to achieve normal or supranormal plasma levels of 100% or 
        higher. Results of studies on protein C concentrate, thrombomodulin or 
        inhibitors of tissue factor are promising, but the efficacy and safety 
        of these novel strategies remains to be established in appropriate 
        clinical trials.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 9617592 [PubMed - indexed for MEDLINE] 




              25: Schweiz Arch Tierheilkd. 1998;140(12):497-505. Related 
              Articles, Links 


        [Disseminated intravascular coagulation and hyperfibrinolysis in dogs 
        with metastasizing mammary carcinoma]

        [Article in German]

        Mischke R, Wohlsein P, Busse L, Pohlenz J.

        Klinik fur kleine Haustiere, Tierarztlichen Hochschule Hannover.

        The alterations of the haemostatic system (platelet count, activated 
        partial thromboplastin time [APTT], thromboplastin time [standard test, 
        modified test], thrombin time, fibrinogen concentration, activity of the 
        coagulation factors II, V, VII, X, VIII:C, IX, XI, XII, of 
        prekallikrein, high molecular weight kininogen, antithrombin III, 
        protein C, plasminogen and alpha 2-plasmin inhibitor, concentration of 
        soluble fibrin and fibrin(ogen) degradation products [FDP], resonance 
        thrombogram) were described in seven dogs with haemorrhagic diathesis in 
        consequence of an infiltrative, growing mammary carcinoma with 
        multifocal invasion of lymphatic and blood vessels. In most of the cases 
        metastases in different organs could be demonstrated. In every case a 
        serious stage of disseminated intravascular coagulation and 
        hyperfibrinolysis was existent. This was indicated by the distinctly 
        increased concentration (p < 0.0001) of soluble fibrin (27.7 [16.0-79.2] 
        micrograms/ml, median [minimum-maximum], reference range [RR.]: < 9.4 
        micrograms/ml) and FDP (340 [50-860] micrograms/ml, RR.: < 18 
        micrograms/ml) as well as a diminished plasma level of nearly all 
        components of the coagulation and fibrinolytic system concerning 
        especially the concentration of fibrinogen (0.16 [0.01-0.46] g/l, RR.: 
        1.17-3.09 g/l), the activity of factors V (30 [21-40]%, RR.: 75-158%) 
        and VIII:C (9 [4-16]%, RR.: 72-136%) as well as the activity of protein 
        C (8 [3-13]%, RR.: 68-139%) (each: p < 0.0001).

        PMID: 9863356 [PubMed - indexed for MEDLINE] 




              26: Semin Thromb Hemost. 1998;24(1):33-44. Related Articles, Links 



        Derangements of coagulation and fibrinolysis in critically ill patients 
        with sepsis and septic shock.

        Vervloet MG, Thijs LG, Hack CE.

        Medical Intensive Care Unit of the University Hospital VU Amsterdam, The 
        Netherlands.

        In patients with sepsis and septic shock, both coagulation and 
        fibrinolysis are activated frequently leading to the syndrome of diffuse 
        intravascular coagulation (DIC). The different mechanisms leading to 
        abnormalities in coagulation and fibrinolysis are discussed in detail. 
        The coagulation and fibrinolytic system appear to be influenced by the 
        septic process largely independently, leading to a procoagulant 
        imbalance between these systems. Coagulation is initiated by 
        mediator-induced expression of tissue factor and is associated with 
        consumption of the natural coagulation inhibitors antithrombin III, 
        protein C, and protein S. As a result, high plasma levels of 
        thrombin-antithrombin complex (TAT) can be found. The effects on 
        fibrinolysis are dominated by (highly) increased levels of plasminogen 
        activator inhibitor type 1 (PAI-1), leading to inadequate fibrinolysis. 
        Although levels of plasminogen activator antigen are increased, its 
        activity is almost completely inhibited by PAI-1. The resulting effects 
        predispose to a procoagulant state, with widespread fibrin deposition, 
        which may be an important mechanism contributing to multiple organ 
        failure. A thorough understanding of the pathophysiological mechanisms 
        underlying the DIC-syndrome is a prerequisite for a rational approach 
        and future therapy for this severe complication of sepsis.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 9515778 [PubMed - indexed for MEDLINE] 




              27: Clin Lab Sci. 1997 Jul-Aug;10(4):212-8. Related Articles, 
              Links 


        Fibrinolysis inhibitors.

        Davis GL.

        Medical Technology Program, Michigan State University, East Lansing 
        48823, USA.

        The fibrinolytic system involves a series of enzymatic reactions that 
        results in the conversion of the proenzyme, plasminogen, into the 
        trypsin-like lytic enzyme, plasmin. The major physiologic target of 
        plasmin is fibrin. Free plasmin in plasma is a nonspecific lytic enzyme 
        that will degrade other proteins such as fibrinogen and coagulation 
        factors V and VIII. Plasmin and activators of plasminogen also play a 
        role in ovulation, embryo implantation, tissue remodeling, and 
        inflammation.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 10169620 [PubMed - indexed for MEDLINE] 




              28: Thromb Haemost. 1997 Jul;78(1):285-96. Related Articles, Links 



        Clinical impact of the plasminogen activation system in tumor invasion 
        and metastasis: prognostic relevance and target for therapy.

        Schmitt M, Harbeck N, Thomssen C, Wilhelm O, Magdolen V, Reuning U, Ulm 
        K, Hofler H, Janicke F, Graeff H.

        Frauenklinik und Poliklinik, Technischen Universitat Munchen, Germany. 
        manfred.schmitt@lrz.tu-muenchen.de

        Extravasation and intravasation of solid malignant tumors is controlled 
        by attachment of tumor cells to components of the basement membrane and 
        the extracellular matrix, by local proteolysis and tumor cell migration. 
        Strong clinical and experimental evidence has accumulated that the 
        tumor-associated serine protease plasmin, its activator uPA 
        (urokinase-type plasminogen activator), the receptor uPA-R (CD87), and 
        the inhibitors PAI-1 and PAI-2 are linked to cancer invasion and 
        metastasis. In cancer, increase of uPA, uPA-R, and/or PAI-1 is 
        associated with tumor progression and with shortened disease-free and/or 
        overall survival in patients afflicted with malignant solid tumors. uPA 
        and/or its inhibitor PAI-1 appear to be one of the strongest prognostic 
        markers so far described. Strong prognostic value to predict disease 
        recurrence and overall survival has been documented for patients with 
        cancer of the breast, ovary, cervix, endometrium, stomach, colon, lung, 
        bladder, kidney, brain, and soft-tissue. Due to the strong correlation 
        between elevated uPA and/or PAI-1 values in primary cancer tissues and 
        the tumor invasion/ metastasis capacity of cancer cells, proteolytic 
        factors have been selected as targets for therapy. Various very 
        different approaches to interfere with the expression or reactivity of 
        uPA or CD87 at the gene or protein level were successfully tested 
        including antisense oligonucleotides, antibodies, enzyme inhibitors, and 
        recombinant or synthetic uPA and uPA-R analogues.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 9198168 [PubMed - indexed for MEDLINE] 




              29: Cah Anesthesiol. 1996;44(3):219-28. Related Articles, Links 


        [Disseminated intravascular coagulations]

        [Article in French]

        Amstutz P, Moyo JS.

        Service de Reanimation, Hopital Saint-Antoine, Paris.

        Disseminated intravascular coagulation (DIC) syndromes can be defined as 
        the formation of fibrin deposits within the microcirculation, occurring 
        in definite clinical situations. Their biological counterpart is a 
        consumption coagulopathy. The clinical profiles of DIC have been well 
        known for decades, are multiform and range from latency to overwhelming 
        haemorrhagic diatheses, including also characteristic but rare 
        situations, such as purpura fulminans, acral cyanosis and pictures 
        resembling thrombotic thrombocytopenic purpura or haemolytic-uraemic 
        syndrome. Biological tests of DIC show a consumption coagulopathy, 
        displayed on the standard haemostasis sheet; along with signs of 
        paracoagulation and/or of secondary fibrinolysis (FDP). New tests have 
        recently been introduced: D-dimers are specific and sensible; 
        Antithrombin-III, protein C and alpha 2-antiplasmin also can sometimes 
        be useful. The knowledge of the pathophysiology of DIC has made advances 
        with passing years. Fibrin deposits may be non-occlusive, and indeed 
        they are swiftly removed by a secondary fibrinolysis. Except in very 
        rare situations, such as those leading to a cortical renal necrosis, and 
        perhaps in some ARDS, there is little evidence relating DIC to organ 
        failure syndromes. Moreover, there is no clear relationship between the 
        severity of the consumption coagulopathy and the prognosis. For 
        instance, the mortality is much lower in abruptio placentae, where the 
        coagulopathy is very severe, than in septic shock, where it is usually 
        moderate. In septic shock, the disorders of haemostasis were related 
        initially to a platelet activation, then to an activation of the contact 
        system (releasing kinins and triggering complement cascade), and 
        nowadays to the activation of the extrinsic coagulation system. The 
        treatment of DIC is mainly the treatment of its cause. Indications for 
        heparin therapy should be strictly limited to a few exceptional 
        circumstances. When haemorrhagic diathesis threatens, FPC and/or 
        platelet transfusion may be indicated. Aprotinin can be useful in rare 
        cases of overwhelming secondary fibrinolysis. Trials with 
        antithrombin-III or C1-esterase inhibitors are in progress.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 9005011 [PubMed - indexed for MEDLINE] 




              30: Biol Chem Hoppe Seyler. 1995 May;376(5):259-67. Related 
              Articles, Links 


        Plasminogen activator inhibitor type 1 in cancer: therapeutic and 
        prognostic implications.

        Pappot H, Gardsvoll H, Romer J, Pedersen AN, Grondahl-Hansen J, Pyke C, 
        Brunner N.

        Finsen Laboratory, Rigshospitalet, Copenhagen-O, Denmark.

        Degradation of the extracellular matrix plays a crucial role in cancer 
        invasion. This degradation is accomplished by the concerted action of 
        several enzyme systems, including generation of the serine protease 
        plasmin by the urokinase pathway of plasminogen activation, different 
        types of collagenases and other metalloproteinases, and other 
        extracellular enzymes. The degradative enzymes are involved also in 
        tissue remodelling under non-malignant conditions, and the main 
        difference appears to be that mechanisms which regulates these processes 
        under normal conditions are defective in cancer. Specific inhibitors 
        have been identified for most of the proteolytic enzymes, e.g. 
        plasminogen activator inhibitors (PAI's) and tissue inhibitors of 
        metalloproteinases (TIMP's). It has been contemplated that these 
        inhibitors counteracted the proteolytic activity of the enzymes, thereby 
        inhibiting extracellular tissue degradation which in turn should prevent 
        tumor cell invasion. This review focuses on plasminogen inhibitor type 1 
        (PAI-1). It is described that PAI-1 is not produced by the epithelial 
        cancer cell but by the stromal cells in the tumors, suggesting a 
        concerted action between stroma and tumor cells in the processes 
        controlling proteolysis in cancer. The specific localization of PAI-1 to 
        the tumor stroma and in many cases to areas surrounding the tumor 
        vessels has lead us to suggest that PAI-1 serves to protect the tumor 
        stroma from the ongoing uPA-mediated proteolysis. This hypothesis is 
        supported by recent clinical data showing increased levels of PAI-1 in 
        metastases as compared to the primary tumor as well as data 
        demonstrating that high levels of PAI-1 in tumor extracts from breast, 
        lung, gastric and ovarian cancer is associated with a shorter overall 
        survival.(ABSTRACT TRUNCATED AT 250 WORDS)

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 7662168 [PubMed - indexed for MEDLINE] 




              31: J Obstet Gynaecol. 1995 Apr;21(2):151-65. Related Articles, 
              Links 


        Urokinase-type plasminogen activator (uPA) and its receptor (CD87): a 
        new target in tumor invasion and metastasis.

        Schmitt M, Wilhelm O, Janicke F, Magdolen V, Reuning U, Ohi H, Moniwa N, 
        Kobayashi H, Weidle U, Graeff H.

        Frauenklinik, Technischen Universitat, Munchen, Germany.

        Extravasation and intravasation of tumor cells in solid malignant tumors 
        is controlled by 3 steps: 1) attachment to and interaction of tumor 
        cells with components of the basement membrane and the extracellular 
        matrix, 2) local proteolysis, and 3) tumor cell migration. Evidence has 
        accumulated that different types of tumor-associated proteases, their 
        inhibitors and receptors are involved in tumor invasion and metastasis. 
        Four different classes of proteases are known to be correlated with the 
        malignant phenotype: 1) Matrix metalloproteases; including collagenases, 
        gelatinases and stromelysins. 2) Cysteine proteases; including 
        cathepsins B and L. 3) Aspartyl protease cathepsin D. 4) Serine 
        proteases; including plasmin and tissue-type plasminogen activator (tPA) 
        and urokinase-type plasminogen activator (uPA). A strong independent 
        prognostic value (relapse-free and/or overall survival) has especially 
        been demonstrated for uPA and its inhibitor PAI-1 in patients with 
        cancer of the breast, ovary, stomach, esophagus, colon, lung, and kidney 
        thus predicting the course of the cancer disease. The strong correlation 
        between elevated uPA and/or PAI-1 values in primary cancer tissues and 
        the malignant phenotype of cancer cells has prompted to explore new 
        tumor biology-oriented concepts in order to suppress uPA or uPA receptor 
        (CD87) expression or to abrogate interaction of uPA with CD87. Various 
        very different approaches to interfere with the expression or reactivity 
        of uPA or CD87 at the gene or protein level were successfully tested 
        including antisense oligonucleotides, antibodies, inhibitors and 
        recombinant or synthetic uPA and CD87 analogues.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 8556577 [PubMed - indexed for MEDLINE] 




              32: Cas Lek Cesk. 1994 Dec 5;133(23):719-22. Related Articles, 
              Links 


        [Diagnosis and therapy of disseminated intravascular coagulation]

        [Article in Czech]

        Maly J, Pecka M, Pidrman V, Blaha M, Siroky O, Jebavy L.

        2. katedra vnitrnich oboru, LF UK, Hradec Kralove.

        The syndrome of disseminated intravascular coagulation (DIC) is an 
        acquired coagulation disorder which is characterized by a significant 
        activation of haemostasis and the formation of intravascular 
        microthrombi, the consumption of coagulation factors and activation of 
        fibrinolysis. DIC has similar clinical stages and a similar laboratory 
        picture, regardless of the causal factor. The diagnosis of DIC should be 
        based on anamnestic, clinical and laboratory data. The laboratory 
        diagnosis of DIC is possible by using relatively simple tests, which 
        have the character of statim examinations. DIC treatment is based on the 
        principle of treatment of the cause, discontinued consumption of 
        haemostatic material, substitution of lacking factors and restoration of 
        the microcirculation. The possible development of DIC must be taken into 
        account in a number of acute conditions, in particular the development 
        of shock syndrome. The presented article summarizes some views on 
        causes, diagnosis and possible treatment of DIC.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 7834668 [PubMed - indexed for MEDLINE] 




              33: Blood Coagul Fibrinolysis. 1994 Oct;5(5):829-32. Related 
              Articles, Links 


        Study of the balance between coagulation and fibrinolysis in 
        disseminated intravascular coagulation using molecular markers.

        Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Morishita E, 
        Yamazaki M, Aoshima K, Matsuda T.

        Department of Internal Medicine (III), Kanazawa University School of 
        Medicine, Japan.

        Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 
        2-plasmin inhibitor complex (PIC) and active plasminogen activator 
        inhibitor (PAI) were assayed in 66 cases of disseminated intravascular 
        coagulation (DIC). Significant elevation of both TAT and PIC was 
        observed in all cases of DIC. Most elevated levels of TAT were seen in 
        DIC with acute promyelocytic leukaemia (APL) and sepsis. The highest 
        levels of PIC were seen in DIC with APL but were much lower in sepsis. A 
        significant elevation in active PAI was observed in DIC due to acute 
        leukaemia (apart from APL), chronic myeloid leukaemia and sepsis, but 
        not in APL, non-Hodgkin lymphoma and cancer. Active PAI was higher in 
        patients with multiple organ failure (MOF) than in those without MOF 
        while PIC was lower in patients with this complication. Thus, the 
        balance of coagulation and fibrinolysis varied according to the 
        underlying cause of DIC; APL had more dominant activation of 
        fibrinolysis, while sepsis had greater activation of coagulation. It is 
        suggested that the inhibition of secondary fibrinolytic activation plays 
        an important role in the progression of MOF by the disturbance of the 
        microcirculation.

        PMID: 7865691 [PubMed - indexed for MEDLINE] 




              34: Anaesthesist. 1994 Jun;43(6):347-54. Related Articles, Links 


        [Diagnosis and therapy of disseminated intravascular coagulation]

        [Article in German]

        Scherer R, Paar D, Stocker L, Kox WJ.

        Institut fur Anasthesiologie, Universitatsklinikum der GHS Essen.

        Consumptive coagulation disorders are frequently observed in critically 
        ill patients secondary to other underlying diseases. Initial 
        hypercoagulability leads to subsequent hypocoagulability due to 
        consumption of procoagulant proteins, inhibitors, and platelets. This 
        process evolves in three distinct phases: an initial increase in 
        coagulation activity is characterised by the activation of coagulation 
        factors and platelets without any clinical symptoms of a haemorrhagic 
        diathesis. The ongoing process of activation and accelerated consumption 
        of coagulation factors and inhibitors causes a critical reduction in the 
        haemostatic potential. The time of onset of the clinical symptoms of 
        bleeding depends on the patient's underlying disease and its 
        pharmacological management. Coagulation processes that are restricted 
        locally under normal conditions become disseminated when the inhibitory 
        potential--mainly represented by antithrombin III (AT III)--is 
        exhausted. Therefore, thrombin formation occurs, especially in the 
        microcirculation, where fibrin clot deposition begins to cause 
        inhomogeneities of blood flow and thus to reduce oxygen delivery to the 
        tissues. Hypocoagulability, reactive hyperfibrinolysis, and diffuse 
        bleeding lead to an irreversible systemic breakdown of haemostatic 
        mechanisms (disseminated intravascular coagulation, DIC). The laboratory 
        diagnosis of accelerated consumption is based on the course of global 
        coagulation tests (e.g., prothrombin time, activated partial 
        thromboplastin time, platelet count) and more sensitive ("dynamic") 
        activation parameters such as prothrombin fragment F1 + 2, thrombin-AT 
        III complex, fibrin monomers, or d-dimer. Measurements of plasminogen, 
        tissue plasminogen activator, plasminogen activator inhibitor 1, and 
        alpha 2-antiplasmin-plasmin complex provide information on fibrinolytic 
        turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 8048768 [PubMed - indexed for MEDLINE] 




              35: Invasion Metastasis. 1994-95;14(1-6):210-22. Related Articles, 
              Links 


        Plasmin in pericellular proteolysis and cellular invasion.

        Kramer MD, Reinartz J, Brunner G, Schirrmacher V.

        Institute for Immunology and Serology, University of Heidelberg, 
Germany.

        Invasive tumor growth or severe inflammation is accompanied by the 
        extravasation of fibrinogen from leaky or damaged blood vessels and the 
        formation of a fibrin clot. The clot provides a matrix for the inward 
        migration ('invasion,' 'infiltration') of tumor cells as well as 
        inflammatory cells. The factors that govern the cell/fibrin interaction 
        are not known. We have explored in vitro the possible role of the 
        cell-surface-associated pathway of plasminogen activation in the 
        adhesion of keratinocytes to fibrin and in the invasion of melanoma 
        cells into fibrin gels. Our experiments provided evidence that 
        generation of plasmin at the cell surface destabilizes the adhesive 
        interaction between keratinocytes and fibrin, most likely by cleaving 
        fibrin into fibrinopeptides and destroying its adhesive capacity. 
        Moreover, we found that plasmin generated at the melanoma cell surface 
        promotes the inward migration of these cells into three-dimensional 
        fibrin matrices. In conclusion, the generation of plasmin at the 
        cellular surface may be an important factor in pericellular proteolysis 
        and the dynamic interaction between cells and fibrin-containing 
        pericellular matrix under conditions of tumor invasion and inflammation.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 7657514 [PubMed - indexed for MEDLINE] 




              36: J Neurooncol. 1994;22(2):173-81. Related Articles, Links 


        Thromboembolic complications associated with brain tumors.

        Sawaya RE, Ligon BL.

        Department of Neurosurgery, University of Texas M.D. Anderson Cancer 
        Center, Houston, USA.

        Thromboembolic complications are the second most common cause of death 
        in hospitalized cancer patients; they are caused by alterations of 
        hemostasis and include hypercoagulable states, acute and chronic 
        disseminated intravascular coagulation, and primary fibrinolysis. The 
        fibrinolytic system is comprised of several serine protease enzymes and 
        their inhibitors and is associated in various biological systems with 
        physiological and pathological events such as tissue development, 
        remodeling, invasiveness, and migratory potentials of both normal and 
        malignant cells. It also plays a key role in the dissolution of fibrin 
        strands. Defective fibrinolysis, which is often associated with the 
        pathogenesis of venous thrombosis and other thromboembolic 
        complications, occurs when the balance is disrupted, resulting in either 
        inhibition or enhancement of fibrinolysis. The association between 
        thromboembolic complications and neoplastic disease has been 
        well-established since Trousseau in 1865 first reported a high incidence 
        of venous thrombosis in a series of patients with gastric carcinoma. In 
        this article, we discuss the factors that have been shown to be 
        associated with thromboembolic complications in patients who harbor 
        brain tumors, namely, hemostatic alterations caused by the tumors 
        themselves or through interactions with neural tissue around the tumors, 
        pre-operative hemostatic alterations in certain patients, and defective 
        fibrinolysis associated with specific tumor types and/or tumor 
locations.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 7745469 [PubMed - indexed for MEDLINE] 




              37: J Natl Cancer Inst. 1993 Aug 4;85(15):1225-30. Related 
              Articles, Links 


        Tumor cell procoagulant and urokinase expression in carcinoma of the 
        ovary.

        Zacharski LR, Memoli VA, Ornstein DL, Rousseau SM, Kisiel W, Kudryk BJ.

        Department of Veterans Affairs Medical and Regional Office Center, White 
        River Junction, Vt.

        BACKGROUND: An association between cancer and increased blood 
        coagulation has been observed for many years. Generally, there is an 
        equilibrium between the coagulation system (fibrin deposition) and the 
        fibrinolytic system (degradation of fibrin by enzymes). However, in 
        malignant disease such as ovarian carcinoma, this equilibrium is 
        disrupted, resulting in the abnormal activation of coagulation or 
        hypercoagulability. Also, evidence indicates that various components of 
        these pathways may contribute to the disorderly characteristics of 
        malignancy, such as proliferation, invasion, and metastasis. PURPOSE: 
        Our purpose was to define the mode of interaction of tumor cells in 
        ovarian carcinoma with both the coagulation (procoagulant-initiated) and 
        fibrinolysis (urokinase-type plasminogen activator-initiated) (u-PA) 
        pathways. METHODS: Studies were performed on 
        acetone-methylbenzoate-xylene-fixed tissue prepared from fresh resected 
        primary tumor specimens from 15 patients with cystic epithelial ovarian 
        carcinoma. None of the patients had received prior treatment. Antibodies 
        were tested on control and tumor tissues in concentrations that provided 
        maximum staining intensity with minimum background staining. Laboratory 
        immunohistochemical techniques used purified, monospecific antibodies to 
        detect coagulant antigens. Tests were performed utilizing antibodies to 
        recombinant human tissue factor; factor VII; factor X; factor XIIIA; 
        high-molecular-weight and low-molecular-weight forms of u-PA; 
        tissue-type plasminogen activator; plasminogen; and the plasminogen 
        activator inhibitors 1, 2, and 3. Monoclonal antibodies used for 
        specific antigen detection included 1-8C6 (fibrinogen), T2G1 (fibrin), 
        and EBM-11 (macrophage-specific). RESULTS: The ovarian tumor cells 
        expressed urokinase-type plasminogen activator in a pattern that was 
        variable in intensity and distribution. Tumor cell plasminogen was not 
        detected. Tumor cells also expressed tissue factor and coagulation 
        pathway intermediates that resulted in local thrombin generation as 
        evidenced by the conversion of fibrinogen (present in tumor connective 
        tissue) to fibrin that was found to hug the surfaces of tumor nodules 
        and individual tumor cells. Detected fibrin could not be accounted for 
        on the basis of necrosis or a local inflammatory cell infiltrate. 
        CONCLUSIONS: These results are consistent with the existence of a 
        dominant tumor cell-associated procoagulant pathway that leads to 
        thrombin generation and hypercoagulability in carcinoma of the ovary. 
        IMPLICATIONS: In ovarian carcinoma the procoagulant pathway may 
        contribute to tumor progression. Clinical trials of therapeutic drugs 
        capable of limiting local coagulability (anticoagulants, protease 
        inhibitors) are indicated in this tumor type.

        PMID: 8331683 [PubMed - indexed for MEDLINE] 




              38: Z Gesamte Inn Med. 1993 Jun-Jul;48(6-7):272-82. Related 
              Articles, Links 


        [The fibrinolytic system and its activators]

        [Article in German]

        Seifried E.

        Abteilung Innere Medizin III, Universitat Ulm.

        The human fibrinolysis system is a proteolytic enzymatic process in the 
        blood. Its purpose is to locally limit intravascular thrombotic 
        processes and to reopen vessels closed by thrombosis. The main enzyme of 
        the fibrinolysis system is the active protease plasmin produced by 
        activation of the inactive first step plasminogen by means of 
        plasminogen activators via limited proteolysis. Thrombolytic therapy 
        with plasminogen mimics and enhances physiological fibrinolysis. The 
        following substances are presently available for clinical use: the 
        non-physiological thrombolytics streptokinase and APSAC (acylated 
        plasminogen-streptokinase activator complex), as well as the 
        physiological plasminogen activators urokinase and tissue plasminogen 
        activator (t-PA). Whereas the first three systemically activate the 
        fibrinolysis system, t-PA possesses relative fibrin selectivity. The 
        fibrin-selective active prourokinase and a recombinant mutant of t-PA 
        with prolonged in vivo half-life have not yet been officially approved 
        for the treatment of thromboembolytic diseases but are being clinically 
        tested. In the development stage are mutants, hybrid enzymes and 
        conjugates aiming at further improvement of this therapeutic concept by 
        means of changing the half-life, thrombus affinity and thrombolytic 
        activity. The development of highly effective antithrombotics will help 
        to further improve the results of thrombolytic therapy.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 8333223 [PubMed - indexed for MEDLINE] 




              39: Kokyu To Junkan. 1993 Mar;41(3):267-70. Related Articles, 
              Links 


        [Activation of coagulation and fibrinolysis in patients with abdominal 
        true aortic aneurysm associated with disseminated intravascular 
        coagulation]

        [Article in Japanese]

        Akaike M, Yokoi K, Wada M, Sebe T, Shigekiyo T, Kawai H, Saito S.

        First Department of Internal Medicine, School of Medicine, University of 
        Tokushima.

        Two cases of abdominal true aortic aneurysm (AAA) associated with 
        disseminated intravascular coagulation (DIC) were reported. Case 1 was 
        an 81-year-old male who was admitted because of hematoma on the left leg 
        and in whom was found by MRI an aortic aneurysm of 14 cm in diameter. 
        Coagulation studies indicated DIC by revealing thrombocytopenia, 
        hypofibrinogenemia and increased level of FDP. DIC was well controlled 
        by surgical repair of the aneurysm after the administration of a small 
        dose of heparin. Case 2 was a 60-year-old male who was admitted because 
        of lumbago and hematoemesis and in whom was found by CT and echography 
        an aortic aneurysm of 5.5 cm in diameter. Coagulation studies indicated 
        DIC by revealing thrombocytopenia and an increased level of FDP. On the 
        2nd hospital day, he suddenly died due to the rupture of the aortic 
        aneurysm. In most of 9 cases with AAA without DIC, plasma levels of 
        thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor 
        complex and FDP-D dimer were also elevated. These findings indicate that 
        the coagulation and fibrinolysis systems were generally activated in 
        patients with AAA, and that DIC tends to occur in patients with a giant 
        aortic aneurysm or an impending ruptured aneurysm.

        Publication Types: 
          Case Reports

        PMID: 8469833 [PubMed - indexed for MEDLINE] 




              40: Thromb Haemost. 1993 Feb 1;69(2):141-6. Related Articles, 
              Links 


        Assessment of the relative contribution of different protease inhibitors 
        to the inhibition of plasmin in vivo.

        Levi M, Roem D, Kamp AM, de Boer JP, Hack CE, ten Cate JW.

        Centre for Haemostasis, Thrombosis, Atherosclerosis and Inflammation 
        Research, University of Amsterdam, The Netherlands.

        It has been shown that the most important inhibitor of plasmin is alpha 
        2-antiplasmin, however, other protease inhibitors are able to inhibit 
        this proteolytic enzyme as well. The contribution of the various 
        protease inhibitors to the inhibition of plasmin in vivo has never been 
        quantitatively assessed. To assess the relative contribution of the 
        different protease inhibitors on the inhibition of plasmin we developed 
        a series of sensitive immunoassays for the detection of complexes 
        between plasmin and the protease inhibitors alpha 2-antiplasmin, alpha 
        2-macroglobulin, antithrombin III, alpha 1-antitrypsin and C1-inhibitor, 
        utilizing monoclonal antibodies that are specifically directed against 
        complexed protease inhibitors and a monoclonal antibody against plasmin. 
        It was confirmed that alpha 2-antiplasmin is the most important 
        inhibitor of plasmin in vivo, however, complexes of plasmin with alpha 
        2-macroglobulin, antithrombin III, alpha 1-antitrypsin- and C1-inhibitor 
        were also detected. Particularly during activation of fibrinolysis 
        complexes between plasmin and inhibitors other than alpha 2-antiplasmin 
        were detected. It was observed that during different situations the 
        inhibition profile of plasmin was not constant e.g. in patients with 
        diffuse intravascular coagulation plasma levels of plasmin-alpha 
        1-antitrypsin and plasmin-C1-inhibitor were increased whereas in plasma 
        from patients who were treated with thrombolytic agents complexes of 
        plasmin with alpha 2-macroglobulin and with antithrombin III were 
        significantly elevated. In conclusion, we confirmed the important role 
        of alpha 2-antiplasmin in the inhibition of plasmin, however, in 
        situations in which fibrinolysis is activated other protease inhibitors 
        also account for the inhibition of plasmin in vivo.(ABSTRACT TRUNCATED 
        AT 250 WORDS)

        PMID: 7681223 [PubMed - indexed for MEDLINE] 




              41: Intensive Care Med. 1993;19 Suppl 1:S8-15. Related Articles, 
              Links 


        Coagulation disorders in septic shock.

        Thijs LG, de Boer JP, de Groot MC, Hack CE.

        Medical Intensive Care Unit, Free University Hospital, Amsterdam, The 
        Netherlands.

        Abnormalities in coagulation and fibrinolysis are frequently observed in 
        septic shock. The most pronounced clinical manifestation is disseminated 
        intravascular coagulation. Recent studies in human volunteers and animal 
        models have clarified the early dynamics and route of activation of both 
        coagulation and fibrinolytic pathways. In healthy subjects subjected to 
        a low dose of either endotoxin or TNF an imbalance in the procoagulant 
        and the fibrinolytic mechanisms is apparent, resulting in a procoagulant 
        state. Also in patients with septic shock a dynamic process of 
        coagulation and fibrinolysis is ongoing with evidence of impaired 
        fibrinolysis. These abnormalities have prognostic significance; the 
        extent of disturbances of coagulation and fibrinolysis is related to the 
        development of multiple organ failure and death.

        Publication Types: 
          Review 
          Review Literature 

        PMID: 8227738 [PubMed - indexed for MEDLINE] 




              42: Nippon Rinsho. 1993 Jan;51(1):15-20. Related Articles, Links 


        [Disseminated intravascular coagulation--pathophysiology]

        [Article in Japanese]

        Matsuda T.

        Kanazawa University School of Medicine, Department of Internal Medicine 
        III.

        The main cause of DIC (disseminated intravascular syndrome) is contact 
        of tissue factor with circulating blood. The main symptoms of DIC are 
        bleeding diathesis caused by consumption coagulopathy and organ 
        dysfunction related to circulatory disturbances due to multiple thrombi. 
        However, the symptoms of DIC differ according to degree of fibrinolysis 
        which is characterized by causal disease of DIC. Usually, enhanced 
        fibrinolysis does not cause organ failure but hemorrhagic diathesis, 
        while impaired fibrinolysis does not cause severe bleeding but organ 
        dysfunction. In almost all cases of acute leukemia and in some cases of 
        solid cancer with DIC, hyperfibrinolysis is common. In cases of severe 
        infection with DIC, impaired fibrinolysis due to abnormal elevation of 
        plasminogen activator inhibitor-1 is frequently seen.

        Publication Types: 
          Review 
          Review Literature 

        PMID: 8433509 [PubMed - indexed for MEDLINE] 




              43: Nippon Rinsho. 1993 Jan;51(1):43-9. Related Articles, Links 


        [Progress in diagnosis of disseminated intravascular coagulation 
        (DIC)--diagnostic criteria of DIC]

        [Article in Japanese]

        Koyama T, Aoki N.

        First Department of Medicine, Tokyo Medical and Dental University.

        DIC is an acquired disorder in which intravascular coagulation may lead 
        to microvascular fibrin formation and a hemorrhagic diathesis. If DIC is 
        acute and severe, fibrin formation may lead to microvascular thrombosis, 
        and consumption of coagulation factors and platelets may result in a 
        hemorrhagic diathesis. Secondary to or simultaneously with coagulation, 
        the fibrinolytic system may be activated, accentuating the bleeding 
        tendency. All the systems involved in DIC, such as coagulation, 
        fibrinolysis, kallikrein-kinin, complement, and possibly other systems 
        are regulated. Coagulation is the central event of DIC. The different 
        coagulation factor derivatives may be generated that can be determined 
        and used as markers for the degree of DIC and for effective control of 
        therapy. Some of the procoagulant and anticoagulant factors are 
        converted in the course of coagulation to their active forms and 
        activation peptides. The active factor is subsequently neutralized by 
        forming a complex with an inhibitor. Hemostatic molecular markers, 
        D-dimer of cross-linked fibrin degradation products (D-dimer), 
        thrombin-antithrombin III complex (TAT), and plasmin-alpha 2-plasmin 
        inhibitor complex (PIC) have all been used for the diagnosis of DIC.

        Publication Types: 
          Review 
          Review Literature 

        PMID: 8433527 [PubMed - indexed for MEDLINE] 




              44: Cancer Metastasis Rev. 1992 Nov;11(3-4):291-311. Related 
              Articles, Links 


        The plasminogen-plasmin system in malignancy.

        Kwaan HC.

        Department of Medicine, Northwestern University Medical School, Chicago, 
        IL.

        The study of the plasminogen-plasmin system has, in the past, 
        contributed much to the understanding of fibrinolysis and thrombolysis. 
        Attention is now focused on the role of the components of this system in 
        many biologic functions. Findings of uPA, its receptor and its inhibitor 
        in many tumor tissues and tumor cell lines, strongly implicate their 
        involvement in tumor invasion, tumor cell proliferation and metastasis. 
        The characteristics of the plasminogen activators, the uPA receptor and 
        the plasminogen activator inhibitors as well as their expression and 
        regulation in tumors and tumor cell lines are reviewed.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 1423820 [PubMed - indexed for MEDLINE] 




              45: Clin Investig. 1992 Aug;70(8):631-6. Related Articles, Links 


        Fibrinolytic mechanisms in tumor growth and spreading.

        Sudhoff T, Schneider W.

        Medizinische Klinik, Heinrich-Heine-Universitat, Dusseldorf.

        The high prevalence of hypercoagulative states in cancer patients has 
        been known for more than a century. Venous thrombosis in gastric cancer 
        was described by Trousseau in 1865 [55]. In 1878, Billroth observed 
        intravascular thrombus formation in association with metastasis [4]. 
        Thrombohemorrhagic complications regularly occur in patients with 
        disseminated malignancy and are related to an increase in fibrinogen and 
        fibrin turnover. During the past decade, clinicians have witnessed 
        considerable advances in the understanding of fibrinolysis. Initially 
        centered on the role as part of a dynamic, hemostatic balance, research 
        began to unravel the pathophysiological contribution of fibrinolysis to 
        tumor progression. The mechanisms of tumor invasion and metastasis 
        formation in cancer are of critical importance, since metastasis is the 
        major cause of treatment failure and death. It has been suggested that 
        cell-associated proteolytic enzymes contribute to tumor aggressiveness 
        [11, 22, 23]. Fibrinolytic mechanisms are involved in a number of 
        physiological processes in which tissue degradation and remodeling 
        occurs. These include disruption of the ovarian follicle during 
        ovulation and blastocyst implantation. These events in part resemble the 
        invasive growth of cancer [37, 47]. Inspired by this hypothesis, the 
        role of fibrinolytic processes in tumor invasion is under intensive 
        study.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 1392438 [PubMed - indexed for MEDLINE] 




              46: Behring Inst Mitt. 1992 Apr;(91):169-82. Related Articles, 
              Links 


        Coagulation and fibrinolysis in cancer.

        Heimburger N, Paques EP, Romisch J.

        Research Laboratories of Behringwerke AG, Marburg, Germany.

        Haemostasis is a system of finely adjusted interactions between cells, 
        enzymatic reaction cascades and inhibitors. Disturbances of this balance 
        occur in many disorders, especially in inflammatory processes, 
        septicaemia and cancer. In such cases malignant cells and infectious 
        organisms activate the plasmatic enzyme cascades, especially of the 
        coagulation and fibrinolysis cascades. The resulting consumption and 
        proteolytic degradation of the regulatory proteins contribute to 
        hypercoagulability and secondarily to reactive fibrinolysis, and these 
        may then lead to local thromboses and haemorrhages. These pathogenic 
        events culminate in disseminated intravascular coagulation (DIC), 
        frequently with organ failure and death. Factors of both plasmatic 
        systems are also "misused" by malignant cells for the purposes of growth 
        and metastasis. Prominent examples of this misuse are the formation of a 
        protective fibrin shield against the endogenous defence mechanisms and 
        the local degradation of tissues for tumor proliferation as well as for 
        cell permeation and invasion. In the search for a potential therapy a 
        number of protease inhibitors, predominantly of enzymes of coagulation 
        and fibrinolysis, have been tested in vivo with regard to their 
        efficacy. So far, however, it has not been possible to find a new 
        uniform treatment principle to inhibit the growth and/or metastasis of 
        different types of tumor. The haemorrhagic diathesis and thromboses 
        frequently associated with tumors are generally treated by substitution 
        with plasma components, especially concentrates of coagulation factors 
        and inhibitors.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 1388019 [PubMed - indexed for MEDLINE] 




              47: Int J Clin Lab Res. 1992;21(3):214-20. Related Articles, Links 



        Changes in the coagulation-fibrinolysis balance of endothelial cells and 
        mononuclear phagocytes: role in disseminated intravascular coagulation 
        associated with infectious diseases.

        Semeraro N, Colucci M.

        Dipartimento di Scienze Biomediche e Oncologia Umana, University of 
        Bari, Italy.

        Over the last few years, evidence has accumulated that the pathogenetic 
        mechanism of disseminated intravascular coagulation encountered in 
        patients with infectious diseases is extraordinarily complex and 
        involves multiple interactions between the microorganism itself and/or a 
        number of mediators, both microorganism derived and host manufactured, 
        and multifunctional cellular systems, namely endothelial cells and 
        mononuclear phagocytes. In particular, infectious agents and mediators 
        shift the coagulation-fibrinolysis equilibrium of these cells towards 
        fibrin formation and accumulation, via enhancement of procoagulant 
        properties and reduction of both anticoagulant and fibrinolytic 
        capacities. New insights into the pathogenetic mechanism may have 
        important implications for the management of infected patients with 
        disseminated intravascular coagulation.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 1591371 [PubMed - indexed for MEDLINE] 




              48: Semin Thromb Hemost. 1992 Jan;18(1):104-16. Related Articles, 
              Links 


        Pathways of coagulation/fibrinolysis activation in malignancy.

        Zacharski LR, Wojtukiewicz MZ, Costantini V, Ornstein DL, Memoli VA.

        Department of Medicine, Dartmouth Medical School, Hanover, New 
Hampshire.

        Recent progress in elucidating the complex and heterogeneous 
        interactions between malignancy and coagulation or fibrinolysis 
        reactions in humans has clarified the pathogenesis of disseminated 
        intravascular coagulation that occurs with malignancy and has revealed 
        evidence for two distinct pathways of growth regulation based on 
        production by tumor cells of initiators of thrombin formation versus 
        plasminogen activators. We have proposed a preliminary classification of 
        tumors (see Table 2) based on these interactions. Type I tumors are 
        those in which the tumor cells are associated with an intact coagulation 
        pathway that leads to thrombin formation at the tumor periphery but in 
        which the tumor cells lack u-PA. Examples of tumors in this category 
        include SCCL, malignant melanoma, and renal cell carcinoma. Type II 
        tumors are those in which the tumor cells express u-PA but lack an 
        associated coagulation pathway leading to thrombin formation. Examples 
        of type II tumors include prostate cancer, colon cancer, breast cancer, 
        and N-SCLC. Type III tumors are those that express neither of these 
        pathways, or exhibit some other pattern of interaction. Obviously, this 
        formulation must be regarded as hypothetical. However, this concept fits 
        with the limited data available to date from clinical trials. More 
        importantly, this hypothesis can be tested further by means of 
        intervention aimed at interrupting pathways relevant to specific tumor 
        types. Characterization of additional tumor types by the methods 
        described should permit amplification of this classification of tumors 
        and other patterns of interaction may be defined. Exploration of the 
        coagulation-cancer interaction holds considerable promise for gaining 
        new understanding of both the coagulation mechanism and tumor biology. 
        Most intriguing is the prospect that imaginative approaches to cancer 
        treatment may be devised that are not only relatively nontoxic and low 
        cost, but also effective.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 1574711 [PubMed - indexed for MEDLINE] 




              49: Dan Med Bull. 1991 Dec;38(6):427-43. Related Articles, Links 


        Haemostasis in oral surgery--the possible pathogenetic implications of 
        oral fibrinolysis on bleeding. Experimental and clinical studies of the 
        haemostatic balance in the oral cavity, with particular reference to 
        patients with acquired and congenital defects of the coagulation system.

        Sindet-Pedersen S.

        Department of Clinical Chemistry, Ribe County Hospital, Esbjerg.

        Activation and inhibition of the haemostatic system was reviewed 
        including the interaction between the four biological systems involved 
        in haemostasis: the vessel wall, the platelets, the coagulation system 
        and the fibrinolytic system. The haemostatic mechanism is initiated at 
        the site of injury through local activation of surfaces and release of 
        tissue thromboplastin, resulting in formation and deposition of fibrin. 
        The coagulation process is regulated by physiological anticoagulants. 
        Activation of fibrinolysis is triggered by the presence of fibrin, and 
        the role of tissue-type plasminogen activators (t-PA) at the site of 
        fibrin formation in particular is emphasized. The process is regulated 
        by physiological inhibitors, of which alpha 2-antiplasmin, 
        histidine-rich glycoprotein and plasminogen activator inhibitor are 
        reported to be of major physiological significance. The role of 
        fibrinolysis in the regulation of the dynamic haemostatic balance is 
        discussed, elucidated through examples of congenital deficiencies of the 
        coagulation and the fibrinoytic system. Pharmacological inhibitors of 
        fibrinolysis (i.e. epsilon-aminocaproic acid and tranexamic acid) and 
        their possible effect on the haemostatic system are described. The 
        systemic effects on the fibrinolytic system of surgery and oral surgery 
        is reviewed, and it is concluded, that oral surgery has insignificant 
        effects on blood fibrinolysis. In contrast, oral surgery induces changes 
        of fibrinolysis in the oral environment; initially the fibrinolytic 
        activity of saliva is reduced, due to the presence of inhibitors of 
        fibrinolysis originating from the blood and the wound exudate. When 
        bleeding and exudation cease, the fibrinolytic activity of the saliva 
        will increase. Plasminogen and plasminogen activator, identified as t-PA 
        are present in the oral environment under physiological conditions. 
        Plasminogen is secreted in the saliva and the sources of t-PA include 
        oral epithelial cells and gingival crevicular fluid. The presence of 
        plasminogen and t-PA in the oral environment implies that when fibrin is 
        present (i.e. after surgery), fibrinolysis is triggered. Haemorrhagic 
        complications to oral surgery in patients without known defects of the 
        coagulation system is reviewed. It is concluded that the investigations 
        conducted to the present day do not permit final conclusions with 
        respect to the pathophysiological role of defects in the coagulation and 
        the fibrinolytic systems for the development of bleeding after oral 
        surgery. Further investigations are necessary in order to clarify these 
        aspects, and should include extensive laboratory analyses to reveal rare 
        congenital defects such as factor XIII- and alpha 2-antiplasmin 
        deficiencies.(ABSTRACT TRUNCATED AT 400 WORDS)

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 1802633 [PubMed - indexed for MEDLINE] 




              50: Nippon Rinsho. 1991 Dec;49 Suppl:81-6. Related Articles, Links 



        [Changes in coagulation and fibrinolysis cascades upon extracorporeal 
        circulation]

        [Article in Japanese]

        Kanamori N, Koiwa F, Uda S.

        Department of Nephrology, Showa University Fujigaoka Hospital.

        PMID: 1839690 [PubMed - indexed for MEDLINE] 




              51: APMIS. 1991 Nov;99(11):981-8. Related Articles, Links 


        Immunohistochemical localization of coagulation, fibrinolytic and 
        antifibrinolytic markers in adenocarcinoma of the lung.

        Nakstad B, Lyberg T.

        Department of Pathology and Surgery, Ulleval University Hospital, Oslo, 
        Norway.

        Extravascular coagulation and fibrinolysis are intimately involved in 
        and modulate cancer cell growth, invasion and metastasis. Samples from 
        resection specimens of patients with primary lung cancer 
        (adenocarcinomas) were tested with monoclonal (MAb) and polyclonal (PAb) 
        antibodies against various factors of the coagulation or fibrinolysis 
        systems, or against antigens of inflammatory or proliferating cells. MAb 
        Ki-67 specific to nuclear antigens of proliferating cells showed a 
        distinct but variable staining of cell nuclei throughout the tumor 
        tissue. Nests of tumor tissue stained with cytokeratin-specific 
        antibodies (PKK1), whereas other parts were negative. Fibrin(ogen) and 
        fibronectin were found throughout the tumor tissue stroma and in the 
        alveolar lining, and the most densely stained areas were at the 
        transition zone between normal and tumor tissue. Fibrinolytic system 
        components like tissue plasminogen activators (t-PA), and urokinase 
        (u-PA), and their inhibitors PAI-1 and PAI-2 were all studied. All 
        specimens were negative for t-PA (except endothelial linings), whereas 
        urokinase-specific antibodies stained loosely packed tumor cells and 
        macrophages within the tumor stromal tissue and alveolar septa. Both 
        PAI-1 and PAI-2 were most prominently expressed within interstitial and 
        alveolar macrophages. A weaker staining of tumor tissue cells was 
        demonstrated. Inflammatory cells like macrophages and T lymphocytes were 
        located in aggregates or diffusely spread within tumor stromal tissue. 
        The inflammatory reaction was most intense at the border between normal 
        lung and tumor tissue.

        PMID: 1720319 [PubMed - indexed for MEDLINE] 




              52: Rinsho Byori. 1991 Mar;39(3):309-14. Related Articles, Links 


        [Coagulation and fibrinolysis parameters in disseminated intravascular 
        coagulation (DIC)]

        [Article in Japanese]

        Nakagawa T, Saito H, Watanabe Y, Sato M, Murakawa E.

        Department of Laboratory Medicine, Niigata Cancer Center Hospital.

        Eighty six plasma samples from 41 patients with suspected disseminated 
        intravascular coagulation (DIC) were divided into 3 groups as follows: 
        Group A, 53 samples from established DIC; Group B, 19 samples from 
        possible DIC; and Group C, 14 samples from probable DIC. The following 
        parameters of coagulation and fibrinolysis were evaluated: 
        thrombin/antithrombin III complex (TAT), plasmin/alpha 2 plasmin 
        inhibitor complex (PIC), D-dimer (D-D) and fibrin monomer (FM). In Group 
        A, TAT and PIC were significantly elevated, being 29.5 +/- 20.7 
        micrograms/l and 7.2 +/- 6.1 mg/l respectively, suggesting marked 
        hypercoagulability and accelerated fibrinolysis. There were no 
        correlations between antithrombin III (ATIII) and TAT, between alpha 2 
        plasmin inhibitor (alpha 2PI) and PIC, or between TAT and PIC, showing 
        the clinical diversity of patients with DIC. In all groups abnormal TAT, 
        PIC and D-D findings were observed in many samples (86-100%), and FM was 
        present in 83%, 63%, and 29% of samples in Groups A, B, and C 
        respectively. In Groups B and C, abnormal findings for TAT, PIC, D-D, FM 
        and alpha 2PI apparently indicated hypercoagulability and accelerated 
        fibrinolysis, even though fibrinogen and platelet count were within 
        normal limits.

        PMID: 1828842 [PubMed - indexed for MEDLINE] 




              53: Blood Rev. 1990 Dec;4(4):245-51. Related Articles, Links 


        Haemostatic problems in acute leukaemia.

        Wilde JT, Davies JM.

        University Department of Haematology, Royal Liverpool Hospital, UK.

        Disseminated intravascular coagulation (DIC) is a frequent complication 
        of acute leukaemia, in particular acute promyelocytic leukaemia. 
        Although procoagulant substances released from leukaemic blast cells may 
        induce DIC by activating conventional coagulation pathways, there is 
        increasing evidence to suggest that direct activation of fibrinogen by 
        proteases released from blast cells may be the predominant mechanism by 
        which DIC is initiated. Primary fibrinolysis has also been proposed as 
        the cause of the haemorrhagic diathesis in some cases of acute 
        leukaemia. Although plasminogen activators have been demonstrated in 
        leukaemic blast cells supporting this view, cases of primary 
        fibrinolysis would appear to be rare. A bleeding tendency attributed to 
        primary fibrinolysis may more often be the result of an exaggerated 
        fibrinolytic response secondary to DIC. The main strategies of treatment 
        for leukaemia associated DIC are rapid initiation of chemotherapy and 
        vigorous blood product support until the DIC resolves once the blast 
        cells have been eradicated. The role of heparin in the management of 
        leukaemia associated DIC remains controversial. There is recent evidence 
        to suggest that heparin therapy does reduce the incidence of 
        haemorrhagic death although it has been recommended that relatively low 
        intravenous doses should be administered initially to reduce the risk of 
        heparin induced haemorrhage.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2076471 [PubMed - indexed for MEDLINE] 




              54: Tidsskr Nor Laegeforen. 1990 Nov 30;110(29):3753-6. Related 
              Articles, Links 


        [The role of proteases in the growth, invasion and spread of cancer 
        cells]

        [Article in Norwegian]

        Buo L, Aasen AO, Karlsrud TS, Johansen HT, Sivertsen SM.

        Institutt for kirurgisk forskning, Rikshospitalet, Oslo.

        Cancer cells show a greater capability than normal cells do to break 
        down proteins in the surrounding tissue. This tissue destruction 
        involving proteolytic enzymes is probably essential for the invasion and 
        metastatic spread of malignant cells. The process takes place through an 
        interplay of proteolytic enzyme systems where plasmin-mediated 
        proteolysis plays an important role. Plasminogen activator activity and 
        receptors for plasminogen activators have been discovered in tumors, 
        mainly in areas with invasive growth and tissue degradation. Patients 
        with malignant diseases often demonstrate abnormalities in their blood 
        coagulation, including hyperaggregability of platelets. Experimental 
        research has shown that therapy with antiplatelet drugs, and prophylaxis 
        with protease inhibitors, can limit spread of tumors.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2274946 [PubMed - indexed for MEDLINE] 




              55: Behring Inst Mitt. 1990 Oct;(86):129-45. Related Articles, 
              Links 


        [Hemostasis, fibrinolysis, proteolysis: interaction with inflammatory 
        reactions]

        [Article in German]

        Romisch J, Schuler E, Paques EP, Heimburger N.

        Forschungslaboratorien Behringwerke AG, Marburg, Bundesrepublik 
        Deutschland.

        Many physiological processes are based on the finely regulated 
        interaction between cells and enzymatic reaction cascades. Mainly 
        proteinases are involved in these processes, which are regulated by 
        inhibitors, principally proteins. If this sensitive balance is 
        disturbed, uncontrolled pathophysiological events can be induced, which 
        are often associated with inflammatory reactions. Characteristic for 
        inflammation are events like contact activation of hemostasis, 
        increasing permeability of blood vessels caused by activation of the 
        Kallikrein-Kinin- and the Complement-system and Plasmin-release induced 
        by activation of fibrinolysis. The following uncontrolled proteolysis, 
        leading to tissue destruction, is mainly associated with the degree of 
        illness. Inflammatory cells excrete besides proteinases also mediators 
        maintaining and increasing these processes. Only when the balance 
        between proteinases and inhibitors is restored, inflammation subsides. 
        Afterwards the controlled course of physiological reactions is possible 
        again.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2252459 [PubMed - indexed for MEDLINE] 




              56: Am J Hematol. 1990 Sep;35(1):45-55. Related Articles, Links 


        Comment in: 
          Am J Hematol. 1991 Dec;38(4):337-8.

        Hemostasis in malignancy.

        Nand S, Messmore H.

        Department of Medicine, Loyola University Stritch School of Medicine, 
        Maywood, IL 60153.

        Hemostatic abnormalities are present in a majority of patients with 
        metastatic cancer. These abnormalities can be categorized as 1) 
        increased platelet aggregation and activation, 2) abnormal activation of 
        coagulation cascade, 3) release of plasminogen activator, and 4) 
        decreased hepatic synthesis of anticoagulant proteins like Protein C and 
        antithrombin III. The abnormal activation of coagulation cascade is 
        mediated through release of Tissue Factor, Factor X activators, and 
        other miscellaneous procoagulants from the plasma membrane vesicles of 
        tumor cells. Macrophages of a tumor-bearing host also produce increased 
        amounts of Tissue Factor. Production of Factor X activators and 
        macrophage Tissue Factor is decreased by warfarin. The ability of the 
        tumor cells to produce platelet-aggregating activity and plasminogen 
        activator parallels their metastatic potential in animal and 
        experimental systems. These studies also show that antiplatelet agents 
        and antibodies against plasminogen activator can suppress the metastatic 
        process. One or more laboratory abnormalities of hemostasis can be shown 
        in up to 95% of patients with metastatic cancer. These abnormalities, 
        however, are unable to predict subsequent development of thromboembolic 
        or hemorrhagic complications. Clinical complications occur in 9-15% of 
        the patients in the form of thrombotic or hemorrhagic disorders. The 
        therapy of tumor-related coagulopathy should be guided by its clinical 
        expression. Subclinical DIC should not be treated. Coumadin is generally 
        ineffective for therapy of thrombosis in cancer patients. There is no 
        consensus regarding the use of heparin in acute promyelocytic leukemia 
        (APL). The defibrination in APL may be from disseminated intravascular 
        coagulation as well as systemic fibrinolysis, as shown by decreased 
        alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid 
        plus heparin therapy may be of benefit.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2202206 [PubMed - indexed for MEDLINE] 




              57: Semin Thromb Hemost. 1990 Jul;16(3):230-5. Related Articles, 
              Links 


        Fibrinolysis and cancer.

        Kwaan HC, Keer HN.

        Department of Medicine, Northwestern University Medical School, Chicago, 
        IL 60611.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2146746 [PubMed - indexed for MEDLINE] 




              58: Blood Coagul Fibrinolysis. 1990 Jun;1(2):153-66. Related 
              Articles, Links 


        Evolution of blood coagulation and fibrinolysis.

        Patthy L.

        Institute of Enzymology, Hungarian Academy of Sciences, Budapest.

        The key steps in the evolution of blood coagulation and fibrinolysis 
        have been reconstructed from an analysis of the molecular evolution of 
        their constituents. The data suggest that the blood coagulation and 
        complement cascades are descendants of an ancestral defence system that 
        served the dual role of immobilization and destruction of invading 
        bacteria and the prevention of loss of body fluids. The enzymes of the 
        fibrinolytic, tissue-remodelling cascades form a distinct group, more 
        closely related to the proteases of the digestive tract than to the 
        components of the blood coagulation and complement cascades. Molecular 
        evolution of these enzymes therefore suggests that they are descendants 
        of an ancestral protease responsible for degradation of extracellular 
        proteins. It is shown that the regulatory extensions of the proteases of 
        the blood coagulation, fibrinolytic and complement cascades were 
        assembled from domains borrowed from other proteins. Most non-protease 
        components of these systems were also constructed by this evolutionary 
        mechanism.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2130927 [PubMed - indexed for MEDLINE] 




              59: Clin Biochem. 1990 Jun;23(3):197-211. Related Articles, Links 


        Biochemical and biological aspects of the plasminogen activation system.

        Mayer M.

        Department of Clinical Biochemistry, Hadassah Medical Center, Jerusalem, 
        Israel.

        Plasminogen activators (PAs) are specific proteolytic enzymes which 
        convert the inactive proenzyme plasminogen to plasmin. The plasmin 
        formed is a potent and nonspecific protease which cleaves blood fibrin 
        clots and several other extracellular proteins. In addition to their 
        primary role in the initiation of fibrinolysis, PAs are implicated in a 
        variety of basic biological processes, such as, degradation of the 
        extracellular matrix, tumor invasiveness, tissue remodelling, and 
        cellular differentiation. This review describes recent observations on 
        the biochemical and biophysical characteristics of the different 
        components of the plasminogen activation system. This complex system 
        includes: the proenzymes of tissue type PA (tPA) and urokinase type PA 
        (uPA); the active enzymes tPA, uPA and plasmin; the substrate 
        plasminogen; several natural inhibitors of PA and plasmin activity; and 
        the cellular receptors that bind the proenzymes, enzymes, and 
        inhibitor-enzyme complexes. Through the coordinated interactions of 
        these components, the location, timing, and extent of potent proteolytic 
        activity is controlled. Recent findings on the structure, properties, 
        biological functions, and regulation of the different components of the 
        plasminogen activation cascade are reviewed. Current methods for assay 
        of the amount and activity of the enzymes, inhibitors, and receptors are 
        described. Observations implying specific functions of the system in 
        health and disease, and its potential utilization for diagnosis are 
        examined. Specifically, the potential application of PAs as laboratory 
        markers of neoplasia, as diagnostic tools in diseases of the blood 
        clotting system, their use for monitoring of thrombolytic therapy, and 
        their possible relevance in certain disease states are described.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 2197030 [PubMed - indexed for MEDLINE] 




              60: Dan Med Bull. 1990 Jun;37(3):210-34. Related Articles, Links 


        The haemostatic balance in groups of thrombosis-prone patients. With 
        particular reference to fibrinolysis in patients with myocardial 
        infarction.

        Gram J.

        Department of Chemical Chemistry, Ribe County Hospital, Esbjerg.

        The concept of the haemostatic balance was reviewed, and its potential 
        role in the regulation of tissue repair and the pathogenesis of 
        thrombotic processes was surveyed. Physiological activation of 
        coagulation appears to be dominated by effects of degenerated and 
        injured cells of the vascular wall causing local release of 
        thromboplastin and exposition of activating surfaces. Inhibition of 
        coagulation impairs its progression and the non-thrombogenic nature of 
        the normal endothelium is chiefly caused by the binding of inhibitory 
        components (antithrombin-III, protein C) to specific receptor sites. 
        Physiological activation of fibrinolysis appears to be triggered by and 
        limited to the fibrin because of a specific affinity to fibrin of 
        plasminogen and plasminogen activators. Systemic activation of 
        fibrinolysis is prevented by primary (alpha 2-antiplasmin) and secondary 
        (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A 
        plasminogen binding protein (histidine-rich glycoprotein), plasmin 
        inhibitors and activator inhibitors appear to contribute to the 
        regulation of the initial phase of fibrinolysis. A deviation from normal 
        of the dynamic balance, regulating fibrin formation and resolution, may 
        lead to a haemorrhagic and/or a thrombophilic state. Described were the 
        optimization of selected methods for assessment of variables involved in 
        the haemostatic balance. An overestimation of plasminogen concentrations 
        in plasma may occur in patients with elevated levels of fibrinogen or 
        fibrin degradation products, when using assays based on the activation 
        of plasminogen by streptokinase followed by the hydrolysis of a 
        synthetic chromogenic substrate. This source of error could be 
        eliminated by presence of fibrinogen in excess in the plasminogen assay, 
        thereby securing maximum stimulation of the plasminogen-streptokinase 
        complex. The presence of cryoglobulin in plasma interferes with the 
        assessment in euglobulins of plasminogen activator activities. 
        Experiments indicate that tissue-type plasminogen activator adsorb 
        cryoglobulins and that a cold-promoted activation of the factor 
        XII-dependent proactivator system of fibrinolysis is related to the 
        presence of cryoglobulins. Experiments supported the existence of an as 
        yet not characterized factor XII-dependent proactivator. Strictly 
        optimized procedures for the preparation of euglobulins for the accurate 
        determination of plasminogen activators were recommended. The 
        determination of plasminogen activator inhibition in plasma was 
        optimized and simplified. The amidolytic assay of antithrombin-III was 
        shown to be influenced by adsorption to laboratory utensils and 
        aggregation of thrombin. This error could be corrected by protection 
        with additives (Tween 80, polyethyleneglycol 6,000), which also improved 
        the solubility of the chromogenic substrates in aqueous media. The role 
        of thrombosis in myocardial infarction was reviewed.(ABSTRACT TRUNCATED 
        AT 400 WORDS)

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2192835 [PubMed - indexed for MEDLINE] 




              61: Semin Cancer Biol. 1990 Apr;1(2):117-26. Related Articles, 
              Links 


        Urokinase-dependent cell surface proteolysis and cancer.

        Blasi F, Verde P.

        Institute of Microbiology, University of Copehagen, Denmark.

        Plasmin formation is an important and complex process in vivo. It 
        involves two enzymes, two inhibitors, the substrate and specific 
        receptors. Plasmin formation, dependent on the urokinase-type 
        plasminogen activator (uPA), is discussed in its biochemical, regulatory 
        and physiological aspects and its involvement in cancer malignancy 
        analysed. The role of cell surface plasminogen activation in the 
        processes of extracellular matrix degradation, basement membrane 
        dissolution and cancer invasiveness and metastasis is now established in 
        a variety of model systems. The ability of cells to produce plasmin on 
        their surface, due to the presence of uPA and plasminogen receptors, is 
        at the basis of the regulation of the plasminogen activating system in 
        vivo. Synthesis, activity and localization of each component can be 
        individually regulated thus providing the system with an enormous 
        flexibility.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2151734 [PubMed - indexed for MEDLINE] 




              62: Blood Coagul Fibrinolysis. 1990 Mar-Apr;1(1):79-90. Related 
              Articles, Links 


        The elastase-mediated pathway of fibrinolysis.

        Machovich R, Owen WG.

        Department of Biochemistry and Molecular Biology, Mayo Clinic and 
        Foundation, Rochester, MN 55905.

        Plasmin and elastase degrade fibrin and inhibit the blood coagulation 
        system by degrading key proteins. Elastase can facilitate plasmin 
        expression via an alternative pathway of plasminogen activation. 
        Elastase modifies plasminogen to yield a zymogen that is a better 
        substrate for activators than native plasminogen. Furthermore, elastase 
        inactivates the inhibitor system of plasmin and plasminogen activators 
        without affecting plasmin and plasminogen activators. While plasmin 
        activity develops from a blood zymogen as a consequence of activators 
        synthesized and secreted by endothelium and possibly other cells, 
        elastase is secreted in an active form primarily by polymorphonuclear 
        leukocytes. Plasmin and elastase may play mutual roles in thrombolysis, 
        inflammation, and tumour invasion and metastasis.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2151710 [PubMed - indexed for MEDLINE] 




              63: Radiology. 1990 Mar;174(3 Pt 2):993-1001. Related Articles, 
              Links 


        Plasminogen activators: pharmacology and therapy.

        Holden RW.

        Department of Radiology, Wishard Memorial Hospital, Indiana University 
        School of Medicine, Indianapolis 46202.

        Biochemical advances are providing new insights into coagulation and 
        fibrinolysis. Integrating this biochemical knowledge into plasminogen 
        activator therapy improves understanding of currently available enzymes. 
        Basic components of the fibrinolytic system are discussed and the 
        chemical structures, pharmacokinetics, dosages, and modes of delivery of 
        current and future plasminogen activators are reviewed.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 2137641 [PubMed - indexed for MEDLINE] 




              64: Cancer. 1990 Feb 1;65(3):481-5. Related Articles, Links 


        Abnormal regulation of coagulation/fibrinolysis in small cell carcinoma 
        of the lung.

        Wojtukiewicz MZ, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Rousseau 
        SM, Stump DC.

        Department of Medicine, Dartmouth Medical School.

        Components of coagulation and fibrinolysis reactions were identified in 
        situ by immunohistochemical staining in fresh frozen sections of small 
        cell carcinoma of the lung tissue. Tumor cells stained positively for 
        tissue factor, a protein that is capable of activating the extrinsic 
        pathway of coagulation (the components of which have been seen within 
        small cell carcinoma of the lung [SCCL] tissue), and for proteins C and 
        S antigens. Fibrin was seen in a focal distribution at the host-tumor 
        interface, indicating that thrombin had acted upon the fibrinogen found 
        throughout the tumor stroma. Staining with a neoepitope-specific 
        antibody, which does not discriminate between fibrinogen fragment D and 
        fibrin fragment D-dimer, was similar to that of the fibrin antibody. 
        High molecular weight urokinase-type and tissue-type plasminogen 
        activators were seen in vascular endothelium, but neither existed within 
        the tumor. Low molecular weight urokinase was found in rare isolated 
        foci of tumor cells primarily adjacent to areas of necrosis. Plasminogen 
        activator inhibitor-3 occurred in tumor cell cytoplasmic blebs and in 
        necrotic tumor cells, but plasminogen activator inhibitors 1 and 2 were 
        not seen. Our data suggest a mechanism for thrombin generation and 
        fibrin formation within SCCL tissues that could support cell 
        proliferation, stroma formation, and preservation. These features could 
        be conductive to perpetuation of this tumor and conceivably could form 
        the basis of the beneficial effects of antithrombotic therapy seen in 
        SCCL.

        PMID: 2153429 [PubMed - indexed for MEDLINE] 




              65: Med Lab Sci. 1989 Oct;46(4):331-46. Related Articles, Links 


        Haemostasis and cancer.

        Francis JL.

        Patients with cancer have an increased incidence of thromboembolic 
        disease and haemostatic abnormalities, and there is considerable 
        evidence that the haemostatic system is involved in the growth and 
        spread of malignant disease. Anti-haemostatic agents have given 
        promising results in the treatment of experimental tumours, and several 
        clinical trials in humans have been initiated. The formation of fibrin 
        around the tumour may be a particularly important factor in malignant 
        dissemination. The precise mechanisms of peri-tumour fibrin deposition 
        remain to be elucidated, but may involve alterations in local vascular 
        permeability and the presence of tumour and/or macrophage procoagulants. 
        In addition to their role in fibrin formation, haemostatic components 
        may also be involved in neovascularisation and angiogenesis.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2693872 [PubMed - indexed for MEDLINE] 




              66: Biochem Biophys Res Commun. 1989 Jul 31;162(2):830-7. Related 
              Articles, Links 


        Mechanism of fibrin-specific fibrinolysis by staphylokinase: 
        participation of alpha 2-plasmin inhibitor.

        Sakai M, Watanuki M, Matsuo O.

        Yakult Central Institute for Microbiological Research, Kunitachi, Japan.

        When the extent of plasminogen activation by staphylokinase (SAK) or 
        streptokinase (SK) was measured in human plasma, SAK barely induced 
        plasminogen activation, whereas SK activated plasminogen significantly. 
        When the plasma was clotted with thrombin, the plasminogen activation by 
        SAK was markedly enhanced, but that of SK was little enhanced. 
        Similarly, in a purified system composed of plasminogen, fibrinogen and 
        alpha 2-plasmin inhibitor (alpha 2-PI, alpha 2-antiplasmin), such a 
        fibrin clot increased the activity of SAK significantly. However, when 
        alpha 2-PI was removed from the reaction system, enhancement of the SAK 
        reaction was not observed. In addition, SAK as distinct from SK, showed 
        very little interference with the action of alpha 2-PI. Plasminogen 
        activation by SAK is thus essentially inhibited by alpha 2-PI, but this 
        reaction is not inhibited in fibrin clots. These results suggest that 
        SAK forms a complex with plasminogen, which binds to fibrin and induces 
        fibrinolysis.

        PMID: 2527034 [PubMed - indexed for MEDLINE] 




              67: J Pharm Belg. 1989 Jul-Aug;44(4):308-14. Related Articles, 
              Links 


        [The physiology of hemostasis: plasma and tissue factors in coagulation 
        and fibrinolysis]

        [Article in French]

        Francois P, Verstraeten L, Dinant JP.

        Coagulation and fibrinolysis are two antagonistic phenomena, the 
        harmonious balance of which results form a perfect regulation of their 
        respective activators and inhibitors. Indeed, the efficacy of the 
        response of the organism to an aggression against the blood vessel and 
        its plasmatic and cellular contents, depends on the capacity of 
        maintaining this balance. The mechanisms involve plasma proteins 
        (factors) endowed with a proteolytic activity, as well as mediators 
        released from injured tissues (endothelium). Coagulation corresponds to 
        the process of fibrin formation (fibrin clump), which assures the 
        consolidation of the platelet clot which was pre-formed during the 
        activation of the platelets. Fibrinolysis consists in the gradual 
        dissolution of this fibrin clump, aimed at re-permeabilization of the 
        vessel at the site of the lesion, and thus at a normalization of the 
        blood circulation at this level. Coagulation and fibrinolysis can hardly 
        be dissociated from primary haemostasis (platelet activation), not only 
        because of their interactions, but also because of their chronology: all 
        these events are, indeed, triggered almost simultaneously, even though 
        the duration varies. The mechanisms that are implicated in 
        thrombo-embolic phenomena are comparable to those of physiological 
        haemostasis. However, it is the imbalance between these events which 
        constitutes the pathological aberration and thus induces the formation 
        of a fibrin-platelet thrombus.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2691642 [PubMed - indexed for MEDLINE] 




              68: Gan To Kagaku Ryoho. 1989 Apr;16(4 Pt 2-1):1246-54. Related 
              Articles, Links 


        [Tumor metastasis and the fibrinolytic system]

        [Article in Japanese]

        Yamamura M, Yamamoto M.

        Dept. of Surgery, Kansai Medical University.

        Metastatic spread of malignant tumor appears to correlate with 
        activation of the fibrolytic system. The role of fibrinolysis in growth 
        and metastasis was examined in Lewis lung carcinoma of mice. The 
        inhibition of fibrinolysis or proteases decreased the primary tumor 
        growth and pulmonary metastasis, whereas the activation of fibrinolysis 
        or proteases increased the number of metastatic foci in the lung. 
        Electronmicroscopically, thrombus formation in the primary site 
        prevented tumor invasion and metastasis formation. Plasminogen activator 
        (PA) content of excised tumors was determined by SDS-PAGE, and major PA 
        was found to be urokinase (UK) type. Immunohistochemical study with 
        specific antisera was done. When tumor cells possessed a high level of 
        UK, laminin and type IV collagen, components of the basement membrane, 
        disappeared from tumor tissues. These findings suggest that PA through 
        protease cascade plays a role in tumor invasion and metastasis. 
        Clinically, patients with advanced cancer are usually in a 
        hypercoagulable state with elevated fibrinogen, and fibrin deposition 
        around tumor mass is a serious problem in cancer chemotherapy. UK 
        infusion prior to 5-fluorouracil increased tissue concentration of 
        antitumor agent. However, development of consumption coagulopathy 
        characterized by progression from hypercoagulable state to disseminated 
        intravascular coagulation has also been found in several cases.

        PMID: 2730023 [PubMed - indexed for MEDLINE] 




              69: Blood Rev. 1989 Mar;3(1):11-7. Related Articles, Links 


        Hemostasis associated with abnormalities of fibrinolysis.

        Aoki N.

        First Department of Medicine, Tokyo Medical and Dental University School 
        of Medicine, Japan.

        Hemostatic plugs consist of platelet aggregates and fibrin mesh 
        containing blood cells and plasma components. Hemostatic efficiency 
        depends on the rate of formation of hemostatic plugs as well as the 
        structural integrity and stability of the formed hemostatic plugs. 
        Fibrin elements are major constituents contributing to the structural 
        integrity and stability, but they are subject to fibrinolytic activity 
        occurring spontaneously after fibrin formation. Fibrinolysis is usually 
        suppressed by endogenous inhibitors. Increase of a profibrinolytic 
        component or deficiency of an inhibitor would result in an accelerated 
        fibrinolysis, causing a premature lysis of hemostatic plugs before 
        restoration of injured vessels, leading to a hemorrhagic tendency. Such 
        a state can be seen typically in patients with congenital deficiency of 
        alpha 2-plasmin inhibitor or a hereditary increase of plasminogen 
        activator, and it is also seen in acquired situations such as 
        amyloidosis, liver cirrhosis, disseminated intravascular coagulation 
        (particularly in patients with acute promyelocytic leukemia) and 
        thrombolytic therapy. The hemorrhagic tendency can be well controlled by 
        an administration of an antifibrinolytic agent: epsilon-aminocaproic 
        acid or tranexamic acid. In contrast to an accelerated fibrinolysis 
        causing a hemorrhagic tendency, retarded fibrinolysis may predispose an 
        individual to a thrombotic tendency. Retarded fibrinolysis may be due to 
        either an increase in plasminogen activator inhibitors or decrease of 
        plasminogen activators. Quantitative or qualitative deficiency of 
        plasminogen may also lead to a thrombotic tendency.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 2650772 [PubMed - indexed for MEDLINE] 




              70: Monatsschr Kinderheilkd. 1988 Dec;136(12):788-94. Related 
              Articles, Links 


        [Therapy of consumption coagulopathies]

        [Article in German]

        Kunzer W.

        Universitats-Kinderklinik, Freiburg i.B.

        The terms "consumption coagulopathy" and "disseminated intravascular 
        coagulation" are used synonymously, though the former expression refers 
        to the process of consuming the haemostatic potential, whereas the 
        latter is based upon the generalized formation of microthrombi. Both 
        terms apply to an acquired disturbance of blood clotting leading to an 
        increased turnover of coagulation factors and platelets by which the 
        production sites are being exhausted. Such a process is triggered off by 
        generalized activation of the haemostatic system: after a period of 
        hypercoagulability, haemostasis changes into hypocoagulability with 
        subsequent haemorrhagic diathesis. Additionally, the generalized 
        activation of the haemostatic system leads to a formation of 
        microthrombi in the microcirculation. Since consumption coagulopathies 
        are bound to be secondary disorders, any underlying disease prone to 
        lead to disseminated intravascular coagulation, should be treated as 
        early and as intensively as possible. Solely by this and by restoring 
        circulatory functions impaired by the underlying disease, it is possible 
        in the majority of cases to stop the consumptive coagulopathy and to 
        repair its sequelae. The shock frequently going along with a consumption 
        coagulopathy requires immediate therapy: correction of hypothermia, 
        treatment of acid-base and electrolyte disorders as well as fighting 
        against hypovalaemia, anuria, and uraemia. Dextran does not serve only 
        as plasma expander, but also corrects hypercoagulability and improves 
        the rheological qualities of circulating blood. If these measures fail 
        to stop the consumptive reaction of blood coagulation and/or fail to 
        restore microcirculation in vital organs, indication for the use of 
        anticoagulants or fibrinolytic drugs is given.(ABSTRACT TRUNCATED AT 250 
        WORDS)

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 3070363 [PubMed - indexed for MEDLINE] 




              71: Ann Emerg Med. 1988 Nov;17(11):1138-47. Related Articles, 
              Links 


        Mechanisms of thrombus formation and lysis.

        Stump DC, Mann KG.

        Department of Medicine, University of Vermont, Burlington, Vermont 
05405.

        Maintenance of a patent vasculature is critical to provide nutrient 
        blood flow to dependent tissues. This is normally facilitated by vessels 
        composed of actively nonthrombogenic endothelium and blood that contains 
        both nonactivated platelets and inactive coagulation proenzymes. 
        Following vessel injury, active hemostasis results from 
        vasoconstriction, adherence and aggregation of activated platelets, and 
        coagulation enzyme activation. The resulting thrombus contains a mixture 
        of blood cells and the insoluble product of coagulation, fibrin, which 
        further stimulates the activation of another blood enzyme system known 
        as the fibrinolytic system. This results in the conversion by 
        plasminogen activators of the circulating plasma proenzyme plasminogen 
        into the active fibrinolytic enzyme plasmin, which dissolves the clot 
        into degradation products. Vascular patency ultimately is restored and 
        healing is thus facilitated. The hemostatic system is highly regulated 
        by a variety of processes. Derangement of regulation can lead to disease 
        manifesting either as thrombosis or hemorrhage. Furthermore, improved 
        understanding of the molecular interactions involved in these processes 
        has led to design of newer therapeutic interventions targeted toward 
        amelioration of the sequelae of thromboembolic disease.

        PMID: 3142314 [PubMed - indexed for MEDLINE] 




              72: Crit Rev Biotechnol. 1988;8(2):131-48. Related Articles, Links 



        Plasminogen activation: biochemistry, physiology, and therapeutics.

        Wun TC.

        Department of Biological Sciences, Monsanto Co., Chesterfield, Missouri.

        The mammalian serine protease zymogen, plasminogen, can be converted 
        into the active enzyme plasmin by vertebrate plasminogen activators 
        urokinase (uPA), tissue plasminogen activator (tPA), factor 
        XII-dependent components, or by bacterial streptokinase. The biochemical 
        properties of the major components of the system, plasminogen/plasmin, 
        plasminogen activators, and inhibitors of the plasminogen activators, 
        are reviewed. The plasmin system has been implicated in a variety of 
        physiological and pathological processes such as fibrinolysis, tissue 
        remodeling, cell migration, inflammation, and tumor invasion and 
        metastasis. A defective plasminogen activator/inhibitor system also has 
        been linked to some thromboembolic complications. Recent studies of the 
        mechanism of fibrinolysis in human plasma suggest that tPA may be the 
        primary initiator and that overall fibrinolytic activity is strongly 
        regulated at the tPA level. A simple model for the initiation and 
        regulation of plasma fibrinolysis based on these studies has been 
        formulated. The plasminogen activators have been used for thrombolytic 
        therapy. Three new thrombolytic agents--tPA, pro-uPA, and acylated 
        streptokinase-plasminogen complex--have been found to possess better 
        properties over their predecessors, urokinase and streptokinase. Further 
        improvements of these molecules using genetic and protein engineering 
        tactics are being pursued.

        Publication Types: 
          Review 
          Review, Academic 

        PMID: 2976309 [PubMed - indexed for MEDLINE] 




              73: Semin Thromb Hemost. 1988 Jan;14(1):126-32. Related Articles, 
              Links 


        Antimetastatic agents. II. Summary of the interactions of tumor cells 
        with blood coagulation factors, platelets, fibrinolytic factors, and 
        inflammatory cells and their soluble mediators: potential for 
        therapeutic interventions.

        Rickles FR, Hancock WW.

        Department of Medicine, University of Connecticut School of Medicine, 
        Farmington 06032.

        Although not reviewed during this session of the Workshop, other 
        reactions in the hemostatic pathways are relevant to tumor-host cell 
        interactions, are potential targets for antimetastatic agents, and are 
        therefore included in Figure 1 and Table 1. For example, elsewhere in 
        this issue of Seminars Loskutoff reviews the recent evidence for the 
        importance of naturally occurring plasminogen activator inhibitors in 
        the regulation of fibrinolysis. Since tumor cells may contain both 
        tissue plasminogen activator and a urokinase-like plasminogen activator, 
        the balance between tumor-mediated fibrin formation and fibrinolysis 
        becomes an important issue in assessing antimetastatic treatment 
        protocols. The relationship of the fibrinolytic pathways to metastasis 
        has been reviewed recently by Dano and colleagues. Clearly, no single 
        therapeutic approach designed to inhibit only one of these complicated 
        interactions between tumor cells and host defense mechanisms is likely 
        to be successful. However, each of the pathways illustrated (Fig. 1) and 
        each of the theoretical steps in the metastatic cascade (Table 1) must 
        be considered in the design of new strategies for the use of 
        antimetastatic agents.

        PMID: 3353730 [PubMed - indexed for MEDLINE] 




              74: Hum Pathol. 1987 Mar;18(3):263-74. Related Articles, Links 


        Physiologic regulation and pathologic disorders of fibrinolysis.

        Francis CW, Marder VJ.

        Physiologic fibrinolysis is a reparative process that occurs in response 
        to hemostatic plug or thrombus formation. The final enzymatic step, 
        fibrin proteolysis, results from a coordinated interaction of enzymes 
        and inhibitors, which produces effective action at the site of the 
        disease and spares the proteins of the blood or uninvolved parts of the 
        vascular system. The agent of fibrinolysis, the enzyme plasmin, is 
        derived from its zymogen (plasminogen) through limited proteolysis 
        effected by plasminogen activators. They can be grouped according to 
        functional and immunologic properties into the tissue type and 
        urokinase-like plasminogen activators. The ability of alpha 2 
        antiplasmin to neutralize efficiently free (nonfibrin-bound) plasmin 
        prevents inappropriate systemic activation of fibrinolysis. This control 
        is superseded in certain conditions, such as with the therapeutic 
        administration of plasminogen activators to lyse pathologic thrombi, 
        when plasmin degrades plasma fibrinogen into degradation fragments (X, 
        Y, D, and E). Degradation of cross-linked fibrin results in distinctive 
        products that are characterized by cross-linked (factor XIIIa-induced) 
        derivatives such as D dimer. Disease states resulting from abnormalities 
        in the fibrinolytic system include both hemorrhagic disorders, resulting 
        from excessive fibrinolysis, and thrombosis, as the result of deficient 
        fibrinolysis. Hyperfibrinolysis can result from pharmacologic 
        administration of activators or from defective inhibition produced by 
        alpha 2 antiplasmin deficiency. Hypofibrinolytic thrombosis can result 
        from hereditary defects, for instance of plasminogen or fibrinogen, or 
        from pharmacologic inhibition of fibrinolysis such as with epsilon 
        aminocaproic acid. Laboratory evaluation of fibrinolysis is useful for 
        monitoring fibrinolytic therapy and assessing thrombotic disorders and 
        bleeding; it also includes the specific measurements of plasminogen 
        activator, plasminogen, plasmin, inhibitors and circulating fibrinogen, 
        and cross-linked fibrin degradation products.

        Publication Types: 
          Review

        PMID: 3546075 [PubMed - indexed for MEDLINE] 




              75: Hum Pathol. 1987 Mar;18(3):275-84. Related Articles, Links 


        Thrombosis and cancer.

        Dvorak HF.

        Abnormal hemostasis is a fundamental property of malignant disease, not 
        merely an epiphenomenon attributable to therapy or to chronic illness. 
        Many types of tumor cells express clotting initiators such as tissue 
        factor and act again late in the coagulation pathway by providing a 
        surface for prothrombinase generation. Thus, entry of tumor cells into 
        the plasma, as during metastasis, may be expected to trigger 
        intravascular clotting. However, and perhaps of greater importance, 
        solid tumors growing outside of the blood vasculature regularly deposit 
        fibrin locally in the tissues. They do so by rendering the 
        microvasculature hyperpermeable, allowing fibrinogen and other 
        plasma-clotting proteins to leak into the extravascular space where 
        procoagulants associated with tumor cells or with benign stromal cells 
        initiate clotting. Both fibrin deposition and turnover in solid tumors 
        proceed at rapid rates. Thus, whether attributable to events in the 
        intra- or extra-vascular space, the result is the same: abnormal 
        clotting and fibrinolysis whose consequences may include protection from 
        host inflammatory cells, modulation of the immune response, and 
        induction of angiogenesis.

        Publication Types: 
          Review

        PMID: 3546076 [PubMed - indexed for MEDLINE] 




              76: Scand J Gastroenterol Suppl. 1987;137:11-8. Related Articles, 
              Links 


        Coagulation and fibrinolysis.

        Nilsson IM.

        Dept. of Coagulation Disorders, University of Lund, General Hospital, 
        Malmo, Sweden.

        The two final phases in the haemostatic process, plasma coagulation with 
        the formation of a fibrin clot, and fibrinolysis leading to the 
        dissolution of fibrin clots, are reviewed. Coagulation may be initiated 
        either by reactions occurring between components of the blood alone, the 
        intrinsic pathway, or by reactions which also involve tissue components, 
        termed the extrinsic pathway. In the diagnosis of coagulation disorders, 
        it is convenient to divide the intrinsic pathway into three phases. In 
        phase 1, resulting in the activation of factor (f) X, are involved f 
        XII, XI, VIII and IX, platelet phospholipids, and calcium. In phase 2, 
        prothrombin is converted to thrombin by f Xa in conjunction with f V, 
        phospholipids, calcium. In phase 3, thrombin converts fibrinogen to 
        fibrin, which is then stabilized by f XIII. Antithrombin III is the most 
        important inhibitor. The key component in fibrinolysis is plasminogen, 
        which under the influence of various activators is converted to plasmin. 
        Plasmin is a serine protease and its main in vivo target is fibrin. 
        Alpha 2-antiplasmin and a fast-acting inhibitor of tissue plasminogen 
        activator are the most important inhibitors.

        Publication Types: 
          Review 
          Review, Tutorial 

        PMID: 3321400 [PubMed - indexed for MEDLINE] 




              77: Cancer. 1986 Oct 1;58(7):1488-92. Related Articles, Links 


        The significance of the fibrin/fibrinogen degradation product in serum 
        of carcinoma patients with hematogenous metastasis.

        Imaoka S, Sasaki Y, Iwanaga T, Terasawa T.

        Fibrin/fibrinogen degradation product (FDP) was measured in 270 cases 
        with various carcinomas. An elevation of FDP (5 micrograms/ml or more) 
        was observed in 68 cases (25%). Of the 68 elevated FDP cases, 5 (82%) 
        were inoperable or received nonradical resection. Forty of those 56 
        cases (71%) showed hematogenous metastasis. FDP in those cases which 
        showed hematogenous metastasis was found to be due to fibrinolysis 
        accompanied by consumption coagulopathy.

        PMID: 3742466 [PubMed - indexed for MEDLINE] 




              78: Nippon Sanka Fujinka Gakkai Zasshi. 1986 May;38(5):719-27. 
              Related Articles, Links 


        [Studies on fibrinolysis and ascites accumulation associated with 
        peritonitis carcinomatosa--effects of protease inhibitors (PI) on MM2 
        ascites tumor growth, ascites accumulation and fibrinolysis]

        [Article in Japanese]

        Shibata J.

        The effects of protease inhibitors(PI), t-AMCHA, gabexate, aprotinin and 
        heparin on the growth of mouse MM2 ascites tumor (MAT) and on several 
        components of fibrinolysis were studied. The drugs were administered 
        intraperitoneally one time daily for 12 days, one day after the tumor 
        transplant. The volumes of ascites, total packed cell volume (TPCV) and 
        fibrinolytic parameters (FDP, whole plasmin, plasminogen activator (PA)) 
        were measured on the 8, 10 and 12th days of therapy. Fibrinolytic 
        activity was assayed by the lysin sepharose affinity 
        chromatography-radio caseinolytic method. Fibrinolytic activity in the 
        ascites increased during the tumor growth. The ascites accumulation as 
        well as levels of FDP, whole plasmin and PA in the drug treated group 
        were significantly decreased when compared to the control group. In 
        these drug-treated groups, MAT cells agglutinated in the abdominal 
        cavity, but in contrast to this, no agglutination was observed in the 
        control group. It was uncertain whether PI directly inhibited tumor 
        growth. The fact that PI inhibited the ascites accumulation and also 
        decreased fibrinolytic activity suggest the involvement of protease in 
        the neoplastic process and indicates another therapeutic approach to 
        malignant ascites tumors.

        PMID: 2425022 [PubMed - indexed for MEDLINE] 




              79: Thromb Res. 1986 Mar 15;41(6):847-54. Related Articles, Links 


        The initiation of fibrinolysis in alpha 2-plasmin inhibitor deficient 
        plasma. Role of fibrin.

        Ichinose A, Aoki N.

        Plasmin activity and fibrin degradation products (FDP) are found in 
        alpha 2-plasmin inhibitor (alpha 2-PI) deficient plasma only when 
        clotted, but are not found when the plasma is not clotted. To determine 
        whether fibrin itself could initiate fibrinolysis without activating 
        coagulation enzymes, fibrin monomers were prepared and added to alpha 
        2-PI deficient plasma. The addition of fibrin monomers resulted in the 
        generation of plasmin activity, a marked increase in FDP concentration, 
        and the release of 125I from 125I-labeled fibrin monomers. Replenishment 
        of the deficient plasma with purified alpha 2-PI abolished the effects 
        of fibrin monomers on the initiation of fibrinolysis. Neither 
        development of plasmin activity, increase of FDP, nor release of 125I 
        was observed. These findings indicate that fibrinolysis can be induced 
        by fibrin itself without activation of coagulation cascade and the 
        induction of fibrinolysis is efficiently blocked by alpha 2-PI.

        PMID: 2939589 [PubMed - indexed for MEDLINE] 




              80: Behring Inst Mitt. 1986 Feb;(79):131-41. Related Articles, 
              Links 


        [Sepsis and blood coagulation]

        [Article in German]

        Muller-Berghaus G.

        Septicemia is frequently accompanied by changes in the plasmatic as well 
        as cellular coagulation systems and by microclot formation. The 
        occurrence of a hemorrhagic diathesis and microthrombosis is best 
        explained by the syndrome disseminated intravascular coagulation (= 
        consumption coagulopathy). Disseminated intravascular coagulation can be 
        initiated by different agents and by different pathways. The activation 
        of coagulation by endotoxin is well studied; it is mediated by synthesis 
        of tissue factor by monocytes and endothelial cells. The formation of 
        microthrombi is caused by the precipitation of circulating soluble 
        fibrin under the influence of localizing factors, and it is observed 
        under conditions of reduced fibrinolysis activation. Furthermore, 
        thrombocytopenia, thrombocytopathy and endothelial cell damage caused by 
        a direct effect of the toxic agent contribute to the bleeding diathesis.

        PMID: 3718402 [PubMed - indexed for MEDLINE] 




              81: Annu Rev Med. 1986;37:187-204. Related Articles, Links 

          
        Concepts of clot lysis.

        Francis CW, Marder VJ.

        Physiologic thrombolysis is efficient, while pathologic aberrations in 
        the fibrinolytic system may result in either thrombotic or hemorrhagic 
        disease. This review considers the molecular interactions involved in 
        fibrinolysis, discusses the normal control mechanisms that provide for 
        localized activation without systemic effects, and describes the 
        molecular mechanism of plasmic degradation of fibrinogen and of 
        cross-linked fibrin. The consequences of excessive or deficient 
        fibrinolysis are discussed and specific examples cited of pathologic 
        hemostasis directly related to abnormalities in the fibrinolytic system.

        Publication Types: 
          Review

        PMID: 2939790 [PubMed - indexed for MEDLINE] 




              82: Crit Rev Oncol Hematol. 1986;4(3):249-301. Related Articles, 
              Links 


        The fibrinolytic system in man.

        Collen D, Lijnen HR.

        The fibrinolytic system comprises a proenzyme, plasminogen, which can be 
        activated to the active enzyme plasmin, that will degrade fibrin by 
        different types of plasminogen activators. Inhibition of fibrinolysis 
        may occur at the level of plasmin or at the level of the activators. 
        Fibrinolysis in human blood seems to be regulated by specific molecular 
        interactions between these components. In plasma, normally no systemic 
        plasminogen activation occurs. When fibrin is formed, small amounts of 
        plasminogen activator and plasminogen adsorb to the fibrin, and plasmin 
        is generated in situ. The formed plasmin, which remains transiently 
        complexed to fibrin, is only slowly inactivated by alpha 2-antiplasmin, 
        while plasmin, which is released from digested fibrin, is rapidly and 
        irreversibly neutralized. The fibrinolytic process, thus, seems to be 
        triggered by and confined to fibrin. Thrombus formation may occur as the 
        result of insufficient activation of the fibrinolytic system and (or) 
        the presence of excess inhibitors, while excessive activation and/or 
        deficiency of inhibitors might cause excessive plasmin formation and a 
        bleeding tendency. Evidence obtained in animal models suggests that 
        tissue-type plasminogen activator, obtained by recombinant DNA 
        technology, may constitute a specific clot-selective thrombolytic agent 
        with higher specific activity and fewer side effects than those 
        currently in use.

        Publication Types: 
          Review

        PMID: 2420482 [PubMed - indexed for MEDLINE] 




              83: Br J Haematol. 1985 Nov;61(3):517-23. Related Articles, Links 


        Blood coagulation and fibrinolysis in heat stroke.

        Mustafa KY, Omer O, Khogali M, Jamjoom A, Gumaa KA, Abu el-Nasr N, Gader 
        MA.

        Blood coagulation and fibrinolysis were assessed in 55 cases of heat 
        stroke who presented with or without bleeding tendencies during the 
        Makkah pilgrimage of 1983. 17 patients were identified to have evidence 
        of disseminated intravascular coagulation (DIC). Bleeders with DIC had a 
        higher incidence of shock and a higher mortality when compared to 
        non-bleeders. Thrombocytopenia and liver cell damage were not limited to 
        cases with DIC. Coagulation factors and serum enzyme studies suggested 
        non-specific tissue damage as the trigger mechanism for DIC possibly 
        proceeding through the extrinsic system of blood clotting. We conclude 
        that the breakdown of haemostasis in heat stroke is multifactorial: 
        thrombocytopenia, liver cell damage and DIC.

        PMID: 4063208 [PubMed - indexed for MEDLINE] 




              84: Rinsho Byori. 1985 Jun;Spec No 63:27-36. Related Articles, 
              Links 


        [Fibrinolysis and disseminated intravascular coagulation]

        [Article in Japanese]

        Ikematsu S.

        Publication Types: 
          Review

        PMID: 2931536 [PubMed - indexed for MEDLINE] 




              85: Folia Haematol Int Mag Klin Morphol Blutforsch. 
              1985;112(6):809-30. Related Articles, Links 


        [Hemostatic mechanisms and malignant tumors]

        [Article in German]

        Kase F, Pospisil J, Hlouskova D.

        The mutual relationships between malignant tumours and mechanisms of 
        blood coagulation are presented in a brief survey. In this connection, 
        the mechanisms of a tumour cell entering the circulation through the 
        vessel well and its leaving into the tissues are discussed, the theory 
        of microtrauma being used for explaining these processes. Subsequently, 
        the alterations to be found in the count and function of thrombocytes 
        after contact with a malignant cell and the impact on this cell by blood 
        platelets are represented. As a third factor the activation of blood 
        coagulation which is exercised by substances with a procoagulatory 
        effect produced by the malignant tissue and the frequently observed 
        thrombosis in the course of neoplastic diseases are dealt with in 
        connection with blood level changes of some coagulation factors. In a 
        fourth section the significance of fibrinolysis, its activation and 
        inhibition as well as the production of fibrinolytic activators by 
        neoplasms are discussed.

        Publication Types: 
          Review

        PMID: 2419210 [PubMed - indexed for MEDLINE] 




              86: Thromb Haemost. 1984 Aug 31;52(1):81-4. Related Articles, 
              Links 


        Changes in plasma levels of protease and fibrinolytic inhibitors induced 
        by treatment in acute myeloid leukemia.

        Velasco F, Torres A, Andres P, Martinez F, Gomez P.

        We have studied the main protease inhibitors of leukocytes, 
        alpha-1-protease (alpha 1-PI), alpha-1-antichymotrypsin (alpha 1-Achy) 
        and alpha-2-macroglobulin (alpha 2-M), as well as different parameters 
        of coagulation and fibrinolysis in 21 cases of acute nonlymphoblastic 
        leukemia (ANLL) before, during and after therapy. Nine of the patients 
        presented signs of DIC, 8 of whom belonged to subtype M3 and to subtype 
        1 M1. The initial alpha 1-PI and alpha 1-Achy levels, which were 
        elevated, increased during the treatment period. There was no 
        significant difference between patients with and without DIC. However, 
        those leukemic patients with DIC showed a significant decrease in 
        plasminogen (p less than 0.005) and fast antiplasmin (p less than 0.01) 
        only during the treatment compared with DIC free patients. All DIC cases 
        demonstrated circulating plasmin-antiplasmin complex (P-AP) both before 
        and during treatment. Independent of a possible proteolytic action of 
        leukocyte enzymes on clotting factors in the clinical course of ANLL 
        (mainly M3 subtype), our results suggest an activation of 
        plasmin-mediated fibrinolysis related to the activation of plasminogen 
        by leukocytes, reactive DIC or both.

        PMID: 6238445 [PubMed - indexed for MEDLINE] 




              87: Eur J Biochem. 1984 May 2;140(3):513-22. Related Articles, 
              Links 


        Initial plasmin-degradation of fibrin as the basis of a positive 
        feed-back mechanism in fibrinolysis.

        Suenson E, Lutzen O, Thorsen S.

        This study deals with the effect of fibrin on the transformation of 
        Glu-plasminogen to Glu-plasmin during fibrinolysis. It focuses 
        particularly on changes in fibrin effector function caused by 
        plasmin-catalysed fibrin degradation. Conversion of 125I-labelled 
        Glu-plasminogen to Glu-plasmin was catalysed by urokinase or tissue 
        plasminogen activator, in the presence of different preparations of 
        progressively degraded fibrin. Plasmin catalysis of Glu-plasminogen and 
        the fibrin (derivative) effector was inhibited by aprotinin. The 
        presence of intact fibrin enhanced the rate of Glu-plasmin formation 
        catalysed by tissue plasminogen activator, but not by urokinase. The 
        presence of initially plasmin-cleaved fibrin, however, increased the 
        rates of Glu-plasmin formation with both activators, as compared to 
        those found with intact fibrin. The rate enhancements induced by initial 
        plasmin degradation of the fibrin effector were associated with an 
        increase in its affinity to both Glu-plasminogen and tissue plasminogen 
        activator, suggesting causal relationships. The weak binding of 
        urokinase was unaffected by fibrin degradation, indicating that effector 
        function was solely exerted on the Glu-plasminogen moiety of 
        urokinase-activated systems. Further degradation of fibrin decreased the 
        stimulating effect on Glu-plasmin formation. This decrease occurred at 
        an earlier stage of degradation with tissue plasminogen activator than 
        with urokinase, indicating that greater integrity of the fibrin effector 
        is necessary for its optimal interaction with the tissue plasminogen 
        activator than with Glu-plasminogen. Concentrations of tranexamic acid 
        that saturate low-affinity lysine-binding sites nearly completely 
        dissociated the binding of Glu-plasminogen to degraded fibrin, but not 
        to intact fibrin. In analogy with the binding of lysine analogues to 
        these sites, the conformation of Glu-plasminogen may be altered by 
        binding to degraded fibrin, thus giving rise to the increased activation 
        rate.

        PMID: 6233145 [PubMed - indexed for MEDLINE] 




              88: Br J Haematol. 1984 Apr;56(4):545-56. Related Articles, Links 


        Plasmin-alpha 2-antiplasmin complexes in bleeding disorders 
        characterized by primary or secondary fibrinolysis.

        Booth NA, Bennett B.

        A two-dimensional immunoelectrophoresis (2DIEP) method detects plasmin 
        complexed to its major inhibitor, alpha 2-antiplasmin, in plasma in the 
        blood of patients during (a) thrombolytic therapy with urokinase, (b) 
        episodes of disseminated intravascular coagulation (DIC) with active 
        fibrinolysis, and (c) episodes of fibrinolytic haemorrhage without 
        evidence of DIC. Clearance of the complexes from the blood is rapid and 
        their detection thus implies active plasmin generation at the time of 
        blood sampling or within the preceding 24 h. Abolition of the complexes 
        using tranexamic acid therapy allowed surgery without bleeding in two 
        previously grossly haemorrhagic patients in group (c). Antithrombin III 
        complexed with activated procoagulants was detected using a similar 
        2DIEP method in only two of four patients with DIC. Abnormalities of 
        alpha 2-macroglobulin were detected on 2DIEP of plasma in the patients 
        studied with proteolytic disorders; these did not appear to reflect 
        complex formation.

        PMID: 6201189 [PubMed - indexed for MEDLINE] 




              89: Bull Cancer. 1984;71(5):481-93. Related Articles, Links 


        [Hemostasis and tumor invasion. Therapeutic implications]

        [Article in French]

        Cattan A.

        Plasminogen activator activity (PAA) has been detected in various tumor 
        cells or in their excretion products. In some cell systems PAA is a 
        symptom of cell transformation, but its amount is questionably 
        correlated with the invasiveness of the tumor cells. Procoagulant and 
        aggregation activities on platelets, have been demonstrated in various 
        tumor cells. There are weakly correlated with the metastatic potential 
        of these cells. In vivo, the treatment of animals by modifiers of the 
        hemostasis, or of the fibrinolysis systems provides contradictory 
        results. Some reduction of metastatic diffusion and increase of life 
        span have been noted with Warfarin. Clinical trials are scarce and their 
        methodology is debatable. When conclusive, a lengthening of the life 
        span has been observed, but not a reduction of the metastatic spread as 
        metastases were still present.

        Publication Types: 
          Clinical Trial 
          Review 

        PMID: 6395923 [PubMed - indexed for MEDLINE] 




              90: Behring Inst Mitt. 1983 Aug;(73):43-55. Related Articles, 
              Links 


        Extrinsic plasminogen activator: a new principle in fibrinolysis.

        Lijnen HR.

        Fibrinolysis in the blood seems to be regulated by specific molecular 
        interactions between plasminogen activator, plasmin(ogen), fibrin and 
        alpha 2-antiplasmin. Plasmin(ogen) contains structures, called 
        lysine-binding sites, which mediate its interaction with fibrin and with 
        alpha 2-antiplasmin. In plasma normally no systemic plasminogen 
        activation by plasminogen activator occurs and plasmin, if formed, is 
        efficiently neutralized by alpha 2-antiplasmin. When fibrin is formed in 
        plasma a small amount of plasminogen is bound via its lysine-binding 
        sites. Plasminogen activator present or released in the blood is 
        strongly adsorbed to the fibrin and activates bound plasminogen in situ. 
        The formed plasmin, which remains transiently complexed to fibrin, both 
        by its lysine-binding site(s) and active center, is only slowly 
        inactivated by alpha 2-antiplasmin, while plasmin which is released from 
        digested fibrin is rapidly and irreversibly neutralized. The 
        fibrinolytic process thus seems to be triggered by and confined to 
        fibrin. An important consequence of this molecular model for 
        fibrinolysis is that specific thrombolysis is only expected with the use 
        of a specific activator, like the physiological extrinsic plasminogen 
        activator, which confines the activation of plasminogen to the fibrin 
        surface. Recent in vitro and in vivo studies have confirmed that the 
        extrinsic plasminogen activator (tissue-type) might constitute a 
        superior thrombolytic agent compared to urokinase or streptokinase.

        PMID: 6236789 [PubMed - indexed for MEDLINE] 




              91: Nippon Geka Gakkai Zasshi. 1983 Aug;84(8):692-702. Related 
              Articles, Links 


        [The experimental study of blood coagulation and fibrinolysis in acute 
        portal vein occlusion]

        [Article in Japanese]

        Nakao A.

        Influence of acute portal vein occlusion on blood coagulation and 
        fibrinolysis have not been fully clarified. In this experimental study 
        in mongrel dogs, 1) changes of blood coagulation and fibrinolysis in 
        portal vein and peripheral vein, 2) histological changes in small 
        intestine and 3) activity of plasminogen activator in small intestine 
        were investigated periodically after acute portal vein ligation with or 
        without heparinized hydrophilic catheter-bypass between portal and 
        femoral vein. All five dogs died 81-130 minutes (mean 105 minutes) after 
        portal vein ligation. On the other hand, all five bypassed dogs survived 
        in good condition for more than four hours. Acute portal venous 
        congestion caused hypercoagulable state in portal system and apparent 
        DIC occurred in portal system 10 minutes after portal vein ligation. 
        Activity of tissue plasminogen activator which was observed mostly in 
        the endothelial cells of vessels in submucosal layers of small intestine 
        decreased rapidly and disappeared within 20 minutes after portal vein 
        ligation. To the contrary, with the use of the catheter-bypass 
        procedure, no significant changes of blood coagulation and fibrinolysis 
        were observed. These results indicate clearly that portal venous 
        congestion is the trigger of hypercoagulable state in portal system, 
        which progresses to irreversible DIC in 20 minutes. With the use of the 
        catheter-bypass procedure, portal vein shut-down is performed without 
        any abnormal coagulation and fibrinolysis in portal bed and systemic 
        circulation.

        PMID: 6687131 [PubMed - indexed for MEDLINE] 




              92: Sem Hop. 1983 Apr 28;59(17):1348-54. Related Articles, Links 


        [Development and dissemination of malignant tumors, and hemostasis]

        [Article in French]

        Kher A, Hilgard P.

        Strong circumstantial evidence suggests that the activation of the 
        hemostatic system is involved in the growth and spread of malignant 
        tumors. Nevertheless, the considerable experimental and clinical data 
        presently available cannot be interpreted in one specific direction. The 
        presence of a fibrin and/or a platelet thrombus in the environment of 
        tumor cells only represents the visible end product of a complex 
        biochemical and biophysical process during which other phenomena like 
        haemodynamic changes and the generation of many biologically active 
        enzymes occur. In the interpretation of experimental studies and 
        clinical trials of anticoagulants in cancer disease, a wider concept of 
        the hemostatic process and its multiple interactions with other 
        biological systems is needed. The complement system, adhesive 
        glycoproteins of the cell surface, chemotaxis, growth factors and 
        prostaglandins are some examples of factors which interact with the 
        hemostatic system as well as with the pathology of cancer. The definite 
        pathogenic connection between the clinically observed hypercoagulability 
        of patients with malignant disease and the biology of tumor growth and 
        tumor dissemination remains unclear. Agents which modify hemostatic 
        reactions must be evaluated in specific tumor categories using carefully 
        controlled prospective trials. The results of such studies on tumor 
        regression and also on longevity will permit to assess the efficacy of 
        these agents as adjuvant therapy in the treatment of cancer.

        Publication Types: 
          Review

        PMID: 6306819 [PubMed - indexed for MEDLINE] 




              93: Cancer Invest. 1983;1(5):369-78. Related Articles, Links 


        Fibrinolytic activity in human tumor tissues.

        Yuen P, Kwaan HC.

        The fibrinolytic activity of 156 malignant and 36 benign solid tumors 
        from autopsy and biopsy specimens was studied by the fibrin slide 
        technique. The inhibitory activity against fibrinolysis was graded 
        according to the lysis time of vascular tissues within the tumor. The 
        results show that all malignant solid tumors, with the exception of 
        prostate carcinoma, demonstrated varying degrees of inhibition of 
        fibrinolysis. Persistently high inhibitory activity was found in 
        squamous cell carcinoma of the esophagus, the respiratory tract, cervix 
        uteri, and skin; carcinoma of uterus; colorectal carcinoma; small cell 
        anaplastic carcinoma of lung; neuroblastoma, carcinoma of bile duct, 
        while malignant tumors of the kidney show a lesser degree of inhibition. 
        In contrast, with the exception of the hydatidiform mole, benign solid 
        tumors show little or no inhibition. A similar absence of fibrinolytic 
        activity is seen in metastatic disease. Further studies of the role of 
        the fibrinolytic system in tumors seems warranted.

        PMID: 6686789 [PubMed - indexed for MEDLINE] 




              94: Cancer Metastasis Rev. 1983;2(3):223-37. Related Articles, 
              Links 


        Inhibition of the arrest of hematogenously disseminated tumor cells.

        Tsubura E, Yamashita T, Sone S.

        Most metastases in patients occur as a result of hematogenous 
        dissemination of tumor cells. This process of metastasis is complex and 
        consists of several steps, foremost of which is the arrest of 
        circulating emboli in capillary beds and the formation of a thrombus at 
        that site. Thrombus formation in the metastasis of human cancer was 
        described first by Billroth in 1878. It was reported that the 
        organization of tumor cell emboli, and the subsequent penetration of 
        tumor cells into the capillary wall, was the first stage of metastasis. 
        Since then, many investigations and observations have been made 
        clinically as well as experimentally to clarify the process (or 
        mechanisms) of tumor cell arrest and how to inhibit it. Coagulative and 
        fibrinolytic pathways were believed to have a main role in thrombus 
        formation. However, other factors responsible for the relationship 
        between tumor cells and the host must be also considered. Elegant and 
        extensive studies by Fidler and Kripke demonstrated that development of 
        metastasis is not a random process, but a selection process of 
        specialized subpopulations of highly metastatic cells within the primary 
        tumors. Biochemical constituents and ionic properties on cell surfaces, 
        deformability or locomotive activities of tumor cells, as well as 
        thrombo-plastic-fibrinolytic activities, are also important factors 
        determining the arrest patterns of circulating tumor cells. On the other 
        hand, host defense factors against tumor cells in the bloodstream have 
        been attracting much attention recently in tumor immunology. Host 
        defense factors relating the arrest of tumor cells to the establishment 
        of metastatic foci seemed difficult to define, since many studies showed 
        contradictory data concerning the influence of immune response on tumor 
        cell arrest. Hemodynamic abnormality may also influence the arrest of 
        tumor cells in the circulation. Hypercoagulability induced from host 
        tissues is greatly associated with the arrest patterns. Platelet 
        activities might affect thrombus formation. Nevertheless, exact 
        explanations of the process or mechanisms inhibiting or enhancing the 
        arrest of tumor cells after hematogenous dissemination have not been 
        obtained. In any event, for cancer treatment, it is important to 
        determine which substances inhibit the arrest of circulating tumor cells 
        and how to prevent hematogenous metastasis. In this review, we will 
        focus upon coagulative and fibrinolytic processes and then upon 
        substances that inhibit the arrest of circulating tumor cells. 
        Furthermore, some comments on the possible clinical applications of 
        inhibitory substances for prevention of cancer metastasis are added.

        Publication Types: 
          Review

        PMID: 6367967 [PubMed - indexed for MEDLINE] 




              95: Cancer Metastasis Rev. 1983;2(2):111-27. Related Articles, 
              Links 


        Cell detachment and metastasis.

        Weiss L, Ward PM.

        Cancer cell detachment in three distinct and critical parts of the 
        metastatic cascade is discussed. The detachment of cancer cells from 
        their parent tumors is an initial early event in metastasis. The site of 
        detachment with respect to proximity to blood vessels may determine the 
        initial dissemination route. Many factors affect cell detachment; we 
        specifically consider the effects of growth-rate, necrosis, enzyme 
        activity, and stress on cell release in terms of metastasis-promoting 
        mechanisms. Detachment is also discussed in relation to active cancer 
        cell locomotion, where localized detachment from the substratum is a 
        prerequisite for translatory movement. The importance of active cell 
        movement in tissue invasion has only recently been assessed, and, in the 
        case of at least some human malignant melanomas, a zone of actively 
        moving cancer cells is believed to precede the growing body of the 
        tumor. The secondary release of cancer cells from temporary arrest sites 
        at the vascular endothelium consequent upon intravascular dissemination 
        is also a major area of investigation. Circulating cancer cells arrest 
        at vascular endothelium or are impacted in small vessels, however, most 
        are released into the circulation and subsequently perish. The blood 
        stream is a hostile environment, and it is probable that cancer cells 
        are sufficiently damaged in translocation by hemodynamic trauma and 
        humoral factors such that they easily detach or are 'sheared-off' the 
        vascular endothelium by blood flow. Another possibility is that in some 
        cases they are processed by 'first organ encounters' and perish before 
        or shortly after arriving in a second organ. Animal studies have shown 
        that, following intravenous injection, 60-100% of the injected dose of 
        viable cancer cells are initially arrested in the lungs, but very few 
        remain after 24 hr. As it is only those retained cells which produce 
        tumors, the mechanisms involved in this secondary release, which occurs 
        in all organs so far examined, are critical to any understanding of the 
        metastatic cascade and metastatic inefficiency. The arrest of cancer 
        cells at the vascular endothelium and their subsequent release have been 
        associated with the presence of platelets, and the deposition of fibrin 
        and manipulation of platelet-aggregating mechanisms and fibrinolysis are 
        discussed in terms of their antimetastatic effects. The role of the 
        reticuloendothelial system, natural killer cells, and polymorphs is 
        discussed in relation to cancer cell clearance from blood vessels and 
        also to inherent cancer cell properties which may act to inhibit their 
        metastasis. Although detachment of cancer cells from a primary tumor may 
        be regarded as metastasis promoting, secondary release of cancer cells 
        may be associated with inhibition of metastasis.

        Publication Types: 
          Review

        PMID: 6352010 [PubMed - indexed for MEDLINE] 




              96: Cancer Metastasis Rev. 1983;2(1):41-73. Related Articles, 
              Links 


        Fibrin as a component of the tumor stroma: origins and biological 
        significance.

        Dvorak HF, Senger DR, Dvorak AM.

        An association between cancer and the coagulation system was suggested 
        by Trousseau more than a century ago and initial reports of fibrin 
        deposition in the stroma of solid tumors date back some 25 years. 
        However, the validity and generality of these observations have only 
        quite recently been established, and their implications for an 
        understanding of tumor biology, metastasis, and therapy are only now 
        coming to be appreciated by investigators in the mainstream of cancer 
        research. This article reviews the current status of fibrin's role in 
        the biology of tumor growth, considering in turn: (1) the evidence that 
        fibrin is present in tumors, the nature of such fibrin, and its relation 
        to plasma fibronectin; (2) the mechanisms by which fibrin may come to be 
        deposited in tumors; and (3) the potential biological and medical 
        significance of tumor-associated fibrin deposition and degradation. 
        Among the last are such important possibilities as a barrier function to 
        the immune response and possible roles in angiogenesis, desmoplasia, and 
        metastasis.

        Publication Types: 
          Review

        PMID: 6193869 [PubMed - indexed for MEDLINE] 




              97: Pathol Biol (Paris). 1982 Dec;30(10):861-7. Related Articles, 
              Links 


        [Development and dissemination of malignant tumors and hemostasis]

        [Article in French]

        Kher A, Hilgard P.

        Strong circumstantial evidence suggests that the activation of the 
        hemostatic system is involved in the growth and spread of malignant 
        tumors. Nevertheless, the considerable experimental and clinical data 
        presently available cannot be interpreted in one specific direction. The 
        presence of a fibrin and/or a platelet thrombus in the environment of 
        tumor cells only represents the visible end product of a complex 
        biochemical and biophysical process during which other phenomena like 
        haemodynamic changes and the generation of many biologically active 
        enzymes occur. In the interpretation of experimental studies and 
        clinical trials of anticoagulants in cancer disease, a wider concept of 
        the hemostatic process and its multiple interactions with other 
        biological systems is needed. The complement system, adhesive 
        glycoproteins of the cell surface, chemotaxis, growth factors and 
        prostaglandins are some examples of factors which interact with the 
        hemostatic system as well as with the pathology of cancer. The definite 
        pathogenic connection between the clinically observed hypercoagulability 
        of patients with malignant disease and the biology of tumor growth and 
        tumor dissemination remains unclear. Agents which modify hemostatic 
        reactions must be evaluated in specific tumor categories using carefully 
        controlled prospective trials. The results of such studies on tumor 
        regression and also on longevity will permit to assess the efficacy of 
        these agents as adjuvant therapy in the treatment of cancer.

        Publication Types: 
          Review

        PMID: 6760066 [PubMed - indexed for MEDLINE] 




              98: Onkologie. 1982 Aug;5(4):186-90. Related Articles, Links 


        [Coagulation disorders in tumors and hemoblastoses]

        [Article in German]

        Zurborn KH, Bernsmeier R, Schamerowski F, Stohr A, Bruhn HD.

        Thromboembolic and haemorrhagic complications are not rarely seen in the 
        course of malignant diseases. The underlying coagulation disorders were 
        investigated by means of coagulation analysis in 61 patients with solid 
        tumors and 60 control persons as well as 51 patients with leukemia and 
        50 control persons. As a cause for the thrombotic diathesis in patients 
        with solid tumors and leukemias can be demonstrated a hypercoagulability 
        (shortened PTT and raised factor VIII activity). In addition we found a 
        raised level of fibrinogen, a hypofibrinolysis (prolonged euglobulin 
        lysis time) and in increased platelet aggregation in patients with solid 
        tumors. Predominantly bleeding complications in leukemias are caused by 
        thrombopenia. Another reason, however, may be an activated fibrinolysis 
        or a clot instability because of the reduction of factor XIII. 
        Pathogenetic mechanisms, underlying the tumor induced coagulation 
        disorders, as for example the release of tumor cell thromboplastins from 
        malignant cells are discussed.

        PMID: 6755331 [PubMed - indexed for MEDLINE] 




              99: Nippon Seirigaku Zasshi. 1982;44(11):633-41. Related Articles, 
              Links 


        [Fluctuations in pulmonary fibrin decomposing activities (plasmin and 
        non-plasmin activities) in an endotoxin DIC model in rats]

        [Article in Japanese]

        Okamoto U, Sasaki K, Nagao N, Naiki I, Nagamatsu Y.

        Non-plasmin fibrinolysis enzyme was extracted from the lung and spleen 
        of conventional rats (Thrombos. Haemostas., 1979), although the enzyme 
        was not found in germfree rats, suggesting the possibility that the 
        enzyme may participate in the defence mechanism of the body. The present 
        study was made in an attempt to determine the behavior of non-plasmin 
        fibrinolysis enzyme of the lung tissue in the DIC model of conventional 
        rats induced by a single injection of bacterial endotoxin. The 
        plasminogen-activator activity of the lung tissue, and the fibrinogen 
        level, platelet count, urea nitrogen and plasminogen-activator activity 
        in the blood were also measured. Examination of the lung tissue in the 
        DIC rats indicated a remarkable increase in non-plasmin fibrinolysis 
        activity and a disappearance of plasminogen-activator activity. 
        Inhibitor studies using t-AMCHA and DFP demonstrated that the increased 
        non-plasmin fibrinolysis activity was not derived from activated 
        plasmin, but from serine protease. The disappearance of 
        plasminogen-activator activity in the lung and increase of 
        plasminogen-activator activity in the blood suggested a release of the 
        activator from the lung into the blood due to the endotoxin injection.

        PMID: 6221092 [PubMed - indexed for MEDLINE] 




              100: Vopr Onkol. 1981;27(7):96-103. Related Articles, Links 


        [Intravascular blood coagulation and its role in malignant neoplasms]

        [Article in Russian]

        Pavlovskii DP.

        PMID: 7023043 [PubMed - indexed for MEDLINE] 




              101: J Surg Res. 1979 May;26(5):581-9. Related Articles, Links 


        Tumor interaction with the fibrinolytic system.

        Malone JM, Gervin AS, Moore WS, Keown K.

        PMID: 439891 [PubMed - indexed for MEDLINE] 




              102: Usp Fiziol Nauk. 1979 Apr-Jun;10(2):3-23. Related Articles, 
              Links 


        [Functional significance of the clotting and anticlotting of the blood 
        in the development of malignant neoplasms in the body]

        [Article in Russian]

        Kudriashov BA, Kalishevskaia TM, Kolomina SM.

        Publication Types: 
          Review

        PMID: 157648 [PubMed - indexed for MEDLINE] 




              103: Patol Fiziol Eksp Ter. 1979 Jan-Feb;(1):3-12. Related 
              Articles, Links 


        [Pathophysiological aspects of malignant tumor metastasis]

        [Article in Russian]

        Tereshchenko IP, Kashulina AP.

        Publication Types: 
          Review

        PMID: 370752 [PubMed - indexed for MEDLINE] 




              104: Vopr Onkol. 1979;25(12):30-6. Related Articles, Links 


        [Role of hemostasis in metastatic spread]

        [Article in Russian]

        Balitskii KP, Sopotsinskaia EB.

        Blood fibrin being deposited around the circulating tumor cells seems to 
        contribute to metastatic spread, thus enhancing the cell implantation. 
        Whereas the same fibrin hampers cells detachment from a tumor node and 
        their further dissemination in the organism. The anticoagulation blood 
        system interfers with the fibrin formation, whereby inhibiting the cell 
        implantation and metastatic spread, but is may also enhance them, 
        contributing to detachment and dissemination of tumor cells. In this 
        respect, to enhance the antimetastatic resistance of the body there must 
        be a balanced interaction between the coagulation and anticoagulation 
        blood systems with an unremoved tumor and the increased anticoagulation 
        function after the tumor node resection especially in the early 
        postoperative period.

        PMID: 516581 [PubMed - indexed for MEDLINE] 




              105: Biol Cybern. 1978 Nov 10;31(1):49-54. Related Articles, Links 



        Silent endocrine tumors. A steady-state analysis of the effects of 
        changes in cell number for biological feedback systems.

        Verveen AA.

        Some tumors of hormonal organs are clinically active, while others are 
        not. The "silent" tumors may be discovered by accident or because of 
        effects due to their increase in size. From a simple steady state 
        analysis of hormonal feedback systems follows that hormonal cell 
        multiplication does not significantly influence the systems steady state 
        behaviour (hence the clinical silence).--Exceptions to this rule occur 
        in three situations: when the gain of the system is low; when the growth 
        concerns cells with isolated sensor or reference functions; or because 
        of the growth of autonomous cells. In many biological systems the 
        dangerous situation of clamping to low levels upon sensor cell 
        multiplication has been prevented by lumping, such as the combination of 
        sensor and comparator functions into sensor-comparator cells.

        PMID: 728491 [PubMed - indexed for MEDLINE] 




              106: Z Gesamte Inn Med. 1978 Sep 1;33(17):613-5. Related Articles, 
              Links 


        [Fibrin deposits and fibrinolysis in pre and early stages of 
        arteriosclerosis]

        [Article in German]

        Kopec M.

        Already in the early stages of atherosclerosis still before the 
        appearance of coarsely visible changes subendothelially fibrin-like 
        material is found in the places of predilection known, which reveals 
        electron-microscopically the typical periodicity. Lesions of the 
        endothelium with increase of permeability, release of coagulation 
        factors and mitogenic substances which stimulate the proliferation of 
        smooth muscle cells always precede. There are several mechanisms for the 
        penetration of fibrinogen or fibrin into the vascular wall, the 
        proportion of which changes with the progressing of the atherosclerosis. 
        They are discussed in detail. Mechanisms of fibrinolysis, in which 
        plasmin or activators of plasmin occupy a key position, effect against 
        this process. By histochemical estimation of this activator the 
        fibrinolytical potential of the vascular system can be investigated 
        under various clinical conditions. For this a series of instances is 
        cited.

        PMID: 151992 [PubMed - indexed for MEDLINE] 




              107: Cancer Treat Rev. 1977 Sep;4(3):213-7. Related Articles, 
              Links 


        Fibrinolysis and antifibrinolytic drugs in the growth and spread of 
        tumours.

        Peterson H.

        In the last few years increased release of fibrinolytic enzymes from 
        malignant cells has been observed, but the significance of this property 
        in relation to malignant growth is still not fully understood. 
        Antifibrinolytic drugs decrease the growth rate of some experimental 
        tumours and might have a similar effect on human malignant tumours. 
        Antifibrinolytic drugs might also decrease the intravascular shedding of 
        tumour cells from primary tumours, but might on the other hand enhance 
        the lodgement of those metastatic tumour cells already in the vascular 
        bed of recipient organs.

        PMID: 589607 [PubMed - indexed for MEDLINE] 




              108: Pol Arch Med Wewn. 1977 Aug;58(2):155-60. Related Articles, 
              Links 


        [Microangiopathic hemolytic anemia in neoplastic diseases]

        [Article in Polish]

        Judkiewicz L, Augustyniak W.

        PMID: 905162 [PubMed - indexed for MEDLINE] 




              109: C R Acad Sci Hebd Seances Acad Sci D. 1977 Jun 
              20;284(23):2411-4. Related Articles, Links 


        [A model of the blood coagulation system]

        [Article in French]

        Iliadis A, Cheruy A, Daver J, Desnoyers P.

        PMID: 143350 [PubMed - indexed for MEDLINE] 




              110: J Med. 1977;8(2):103-14. Related Articles, Links 


        Platelet-cancer cell interaction in metastasis formation: a possible 
        therapeutic approcach to metastasis prophylaxis.

        Gastpar H.

        The mechanism of the early stage of metastasis formation by sticky 
        blood-born cancer cells is discussed. Abnormal platelet aggregation to 
        circulating and lodged cancer cells, as well as alterations of blood 
        coagulation and fibrinolysis play an important role. The reducing effect 
        of several platelet aggregation inhibitors on cancer cell stickiness and 
        tumor embolism mortality has been investigated in rats after intravenous 
        transplantation of 1 X 10(6) Walker-256 carcinosarcoma cells. The tested 
        substances diminished platelet aggregation to circulating cancer cells, 
        leading to a dose-dependent inhibition of cancer cell lodgment to the 
        endothelium. Furthermore, some of the substances prevented lethal 
        pulmonary tumor cell embolism which was observed in 60% of the controls. 
        These results are interpreted by assuming an inhibition of disseminated 
        intravascular coagulation which occured after intravenous 
        transplantation of Walker-256 carcinosarcoma. On this basis a clinical 
        long-term study for metastasis prophylaxis was started more than 4 years 
        ago with one of the tested substances, the dipyridamole derivative RA 
        233, in 40 patients with sarcoma or malignant lymphoma of the head and 
        neck region. The provisional results obtained in matched pairs are 
        discussed.

        PMID: 268396 [PubMed - indexed for MEDLINE] 




              111: Angiology. 1976 Oct;27(10):557-67. Related Articles, Links 


        Thrombophlebitis and cancer. A review.

        Oster MW.

        Thrombophlebitis has been associated with virtually all cancers, 
        especially gastrointestinal, urogenital, and lung neoplasms. Although 
        occurring infrequently in cancer patients, thrombophlebitis may appear 
        before the cancer has become symptomatic and may lead to an earlier 
        diagnosis of cancer. The phlebitic syndrome associated with cancer, 
        although not unique, is distinctive. It is often recurrent and 
        migratory, often involves unusual locations, and is often resistant to 
        anticoagulation therapy. Pulmonary emboli are frequent complications. 
        The pathogenesis of phlebitis in cancer patients is not well understood. 
        Evidence suggests that many cancer patients are hypercoagulable, with 
        abnormalities in platelets, coagulation factors, and the fibrinolytic 
        system. These changes may results from the elaboration of 
        thromboplastin-like substances from the cancer tissue.

        Publication Types: 
          Review

        PMID: 802883 [PubMed - indexed for MEDLINE] 




              112: Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1976 Aug 
              30;86(3):263-77. Related Articles, Links 


        Thrombogenic activity of mouse and human tumors: effects on platelets, 
        coagulation, and fibrinolysis, and possible significance for metastases.

        Gasic GJ, Koch PA, Hsu B, Gasic TB, Niewiarowski S.

        Twelve mouse tumors and 29 human malignancies were assayed in vitro for 
        their capacity to aggregate platelets and induce release of 
        radiolabelled serotonin, and for their ability to coagulate blood plasma 
        and digest the fibrin clot. It was discovered that many human and mouse 
        tumors can induce release of radiolabelled serotonin but that the 
        quantitative relationships between this activity of tumors and their 
        capacity to aggregate platelets was variable, permitting tumors to be 
        classified into 3 different types. The procoagulant and fibrinolytic 
        activity was also quite variable. Since no correlation was found between 
        the 4 assayed tumor activities they appear to be independent, separate 
        thrombogenic properties of tumors. Although the information gathered by 
        this study is still fragmentary, some speculations can be made about the 
        role of these activities in treatment of malignant tumors and in 
        determing patterns of body distribution and control of metastases.

        PMID: 136101 [PubMed - indexed for MEDLINE] 




              113: J Invest Dermatol. 1976 Jul;67(1):110-8. Related Articles, 
              Links 


        The blood vessels of the skin.

        Ryan TJ.

        During the last 25 years, cutaneous biologists have been particularly 
        interested in abnormal cutaneous vascular patterns, the profusion of 
        capillary anastomoses, the leakiness of venules, clotting, fibrinolysis, 
        and blood viscosity. As a result, the effects of hypoxia and the factors 
        that encourage new vessel proliferation are better understood than 
        before. Only when the biologic behavior of the two extremes of growth 
        from hypoplasia to hyperplasia is studied and compared can the blood 
        supply of a tissue be understood. Hyperplastic tissues are seen in 
        wounds, psoriasis, cancer, and in selected sites of chronic stasis and 
        hypoxia where the vessels are extremely permeable, where blood cells 
        easily escape, and where lymphatics dilate and proliferate. The 
        proliferation of other tissues, such as endothelium, epithelium, mast 
        cells, and probably of locally infective organisms, is also encouraged 
        in hyperplasia. Moreover, fibrinolysis does not occur and fibrin is 
        deposited, the electrostatic charge on the internal vascular surface 
        becomes more positive, and the organ is more vulnerable to subsequent 
        injury. Atrophic or hypoplastic tissues have a reduced cellular turnover 
        and are less hypoxic. The vessels are less permeable, blood cells do not 
        escape, there is only a slight tendency to clot, and fibrinolysis is 
        often increased. Lymphatics are sparse and infection is not a feature. 
        The electrostatic charge on the internal surface of the vessel is 
        negative.

        Publication Types: 
          Review

        PMID: 778283 [PubMed - indexed for MEDLINE] 




              114: Dtsch Med Wochenschr. 1976 Apr 30;101(18):720. Related 
              Articles, Links 


        [Letter: Blood coagulation and tumor spreading]

        [Article in German]

        Gross R.

        PMID: 1261408 [PubMed - indexed for MEDLINE] 




              115: Sov Med. 1976 Apr;(4):45-51. Related Articles, Links 


        [Changes in the blood coagulation system and fibrinolysis during growth 
        and metastasis of malignant neoplasms]

        [Article in Russian]

        Bergut FA.

        Publication Types: 
          Review

        PMID: 790595 [PubMed - indexed for MEDLINE] 




              116: Haematologia (Budap). 1976;10(3-4):331-7. Related Articles, 
              Links 


        Effect of potato protease inhibitor on the clotting system and 
        fibrinolysis in the dog.

        Worowski K, Glowinski S.

        The potato inhibitor of proteolytic enzymes was found to inhibit the 
        plasma clotting and fibrinolytic systems in the dog. The anticoagulative 
        action of potato inhibitor consists in a prolongation of clotting time, 
        inhibition of thromboplastin generation, reduction of prothrombin 
        consumption and of the retractility of the blood clot. The potato 
        inhibitor prolongs the euglobulin fibrinolysis time and causes a rise in 
        the plasma antiplasmin level.

        PMID: 1028667 [PubMed - indexed for MEDLINE] 




              117: Nippon Rinsho. 1974 May 10;32(5):1074-7. Related Articles, 
              Links 


        [Coagulation, fibrinolysis and various diseases: cancer]

        [Article in Japanese]

        Nira H, Yamashita T.

        PMID: 4858911 [PubMed - indexed for MEDLINE] 




              118: Va Med Mon (1918). 1970 May;97(5):310-4 passimass. Related 
              Articles, Links 


        A review of the basic mechanisms of fibrinogen to fibrin conversion and 
        of fibrinolysis: intravascular coagulation versus primary fibrinolysis.

        Colick JA, Fisher LM.

        Publication Types: 
          Review

        PMID: 4276992 [PubMed - indexed for MEDLINE] 



              Summary Brief Abstract Citation ASN.1 MEDLINE XML UI List LinkOut 
              Related Articles Cited in Books Domain Links 3D Domain Links GEO 
              DataSet Links Gene Links Genome Links GEO Links Nucleotide Links 
              OMIM Links PMC Links Cited in PMC PopSet Links Protein Links SNP 
              Links Structure Links UniSTS Links  Show: 5 10 20 50 100 200 500 
              Sort Author Journal Pub Date Text File Clipboard E-mail Order 
                  Items 1-118 of 118One page.


         
         
       Write to the Help Desk 
      NCBI | NLM | NIH 
      Department of Health & Human Services 
      Freedom of Information Act | Disclaimer
      Dec 22 2003 07:15:02
 