Semin Thromb Hemost. 2002 Feb;28(1):39-44.  Related Articles, Links  

  
Platelets and cancer: implications for antiangiogenic therapy.

Trikha M, Nakada MT.

Department of Oncology Research, Centocor, Malvern, Pennsylvania 19355, USA. trikham@centocor.com

Thromboembolism is one of the most common causes of death in cancer patients. Among the most frequent thrombotic complications in patients with cancer are disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and thrombocytosis. Clearly, these complications arise as tumor cells interact with almost all components of the hemostatic system including platelets. Platelets participate in tumor progression by contributing to the metastatic cascade, protecting tumor cells from immune surveillance, regulating tumor cell invasion, and angiogenesis. Platelets contain one of the largest stores of angiogenic and mitogenic factors and the tumor vasculature is leaky, which allows platelets to come in contact with the tumor and deposit multiple angiogenic factors including vascular endothelial growth factor (VEGF) and thrombin to tumor cells, which in turn contributes to tumor progression. This article reviews the recent literature on how platelets contribute to tumor growth, angiogenesis, and metastasis.

Publication Types: 
Review 
Review, Tutorial 

PMID: 11885024 [PubMed - indexed for MEDLINE] 



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] 

DO RELATED ARTICLES SEARCH PMID: 1388019



 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] 





"An hypercoagulable state is observed in cancer patients, as shown by
abnormal "routine" blood tests found in up to 90% of these patients, as well
as increased levels of specific markers of coagulation activation.
Clinically, these abnormalities are expressed as thrombosis, hemorrhage or
low grade or fulminant disseminated intravascular coagulation. The
pathophysiology of this thrombophilic state is complex and due to
interactions of tumor cells and their products with host cells. Cancer
patients are thus at high risk of thrombosis..." [1]

Definitions & Conditions:

Thrombosis is the formation, development, or presence of a clot[also called
a thrombus].

Disseminated Intravascular Coagulation, or DIC, is a condition in which all
of the clotting elements, factors, platelets & etc., all clot, all at the
same time.  What happens then is that there are NO clotting agents available
because they have been used up, and these people bleed, become covered in
bruises and bleed internally as well.  This condition can present
catastrophically.

However, the more usual presentation of DIC in a cancer patient is a low
grade clotting tendency, with multiple minor episodes.

Paraneoplastic Syndromes: These are collections of symptoms that occur when
people have cancer.  The syndromes differ from person to person and cancer
to cancer.  Often Tumor Secretions play a part.  Development of auto-immune
disease also occurs.

Auto-Immune disease occurs when people make antibodies to their own tissues.
And try to destroy their own tissues.  When auto-immune antibodies are made
to blood vessel walls, either artery walls or vein walls, there will be an
increased incidence of clotting in those vessels.

Trousseau's Syndrome is a migratory thrombophlebitis [inflammation of the
veins associated with clotting] associated with cancer and believed to be an
autoimmune phenomenon.

Endocarditis [inflammation of the inner walls of the heart] that is not
bacterial can occur with cancers,and cause arterial emboli.  We are familiar
with Pulmonary Emboli, the usual cause of which is fragments of clot
breaking off from a large clot in the large vein of a leg.  These fragments
travel to the heart, and pass into the Pulmonary circulation, where they
eventually plug a pulmonary arterial vessel.

Embolus/emboli : A clot or other plug brought by the blood from another
vessel and forced into a smaller one, so as to obstruct the circulation.
Once emboli reach or are generated in the heart, they can travel to any
organ, including the brain.

Tumor growth in the heart chambers or on the valves can also cause
embolization, either of the tumor or of clot that may form around the tumor.
LMS can metastasize to the heart, but this is rare.

Thrombocytosis:  High platelet[thrombocyte] counts in the blood.  Many
cancer patients have high platelet counts, either heralding lung tumors or
as a result of inflammatory conditions.  If the platelet counts get too high
[like 1,000], they actually require treatment to prevent clotting problems.

Dehydration, because of decreased fluid intake due to feeling ill, loss of
appetite, or vomiting, is a
predisposing factor to clotting.

Lack of movement: post operatively, or because of feeling ill, or various
amputations, also predisposes to clotting.

Surgery:  there is a hypercoagulable state after surgery.

~~~~~~~~~
1. Ann Biol Clin (Paris) 2000 Nov-Dec;58(6):675-82
[Venous thrombosis and cancer] [Article in French]
Gouin-Thibaut I, Samama MM.
Service d'hematologie biologique, Groupe hospitalier
Charles-Foix-Jean-Rostand, 7, av de la Republique, 94205, Ivry-sur-Seine.
~~~~~~~~~~~~~~
Just for fun, I will add that there has been noted the development of
Hemophilia in some cancer patients, who developed auto-antibodies to their
Clotting Factor VIII.
~~~~~~~~~~
doreen
with thrombocytosis and paraneoplastic autoimmune phenomena since before the
first surgery. On daily aspirin.
~~~~~
 Ann Biol Clin (Paris). 2000 Nov-Dec;58(6):675-82.  Related Articles, Links  


[Venous thrombosis and cancer]

[Article in French]

Gouin-Thibaut I, Samama MM.

Service d'hematologie biologique, Groupe hospitalier Charles-Foix-Jean-Rostand, 7, av de la Republique, 94205, Ivry-sur-Seine.

The incidence of newly diagnosed cancer is increased, among patients with idiopathic venous thromboembolic event (VTE), six to twelve months after the diagnosis. Among these cancers, the most common sites are colorectal, prostate, pancreas, lung and ovary cancers. However, no study has provided convincing evidence that a patient with idiopathic VTE should undergo an extensive search for underlying cancer. An hypercoagulable state is observed in cancer patients, as shown by abnormal "routine" blood tests found in up to 90% of these patients, as well as increased levels of specific markers of coagulation activation. Clinically, these abnormalities are expressed as thrombosis, hemorrhage or low grade or fulminant disseminated intravascular coagulation. The pathophysiology of this thrombophilic state is complex and due to interactions of tumor cells and their products with host cells. Cancer patients are thus at high risk of thrombosis and so far no biological test can predict the VTE. In special conditions, as surgery or during chemotherapy, prophylaxis with various forms of heparins or oral anticoagulant are recommended.

Publication Types: 
Review 
Review, Tutorial 

PMID: 11098164 [PubMed - indexed for MEDLINE] 


Neurosurgery. 1994 Mar;34(3):389-94; discussion 394-5.  Related Articles, Links  

  
Abnormal coagulation profile in brain tumor patients during surgery.

Iberti TJ, Miller M, Abalos A, Fischer EP, Post KD, Benjamin E, Oropello JM, Wiltshire-Clement M, Rand JH.

Department of Surgery, Mount Sinai Medical Center, New York, New York.

Neurosurgical patients are at high risk for the development of thrombosis and thromboembolism. We compared the perioperative clotting factor and coagulation parameters of 20 patients undergoing elective craniotomy for brain tumors to those of 20 patients undergoing elective abdominal surgery. We also measured the levels of plasma arginine vasopressin to determine if changes in this hormone might be associated with changes in clotting factors, activated partial thromboplastin times, or bleeding times. The results demonstrated a significant reduction in partial thromboplastin times and bleeding times in the neurosurgery group, which began at the initiation of surgery and lasted to the end of the study (12 h postoperatively). Elevations in factor assays and plasma arginine vasopressin occurred in both groups during surgery, but there were no differences between the neurosurgical and abdominal surgical patients, except with Factor IX levels, which were elevated only in the neurosurgical patients. Serum osmolality and hemoglobin levels were significantly higher in the neurosurgical cohort. These results suggest that there are hemostatic differences between neurosurgical patients with brain tumors and abdominal surgery patients that cannot be explained solely by elevations in plasma arginine vasopressin or the clotting factors measured; these differences may be the consequence of perioperative variables such as dehydration and hyperosmolality.

PMID: 8190212 [PubMed - indexed for MEDLINE] 


Chest. 1992 Dec;102(6 Suppl):640S-644S.  Related Articles, Links  


Pathogenesis of venous thrombosis.

Mammen EF.

Department of Pathology, Wayne State University School of Medicine, Detroit.

This brief review attempts to describe the present understanding of the pathogenesis of venous thrombosis in general with special reference to venous thromboembolism in spinal cord injury patients with paralysis. The component parts of Virchow's triad are examined. Most venous thrombi seem to originate in regions of slow blood flow, ie, the large venous sinuses of the calf and thigh or in valve cusp pockets. Decreased blood flow or even stasis due to lack of the pumping action of the large muscle packages in paralyzed patients is undoubtedly one of the major factors. As blood pools, activation products of the coagulation system accumulate locally leading potentially to local hypercoagulability. Activation products of clotting and fibrinolysis can induce endothelial damage which in turn leads to further activation of the hemostasis system. Endothelial damage may also result from distension of the vessel walls by the pooling blood. Blood flow is further decreased by hyperviscosity due to elevated fibrinogen levels and dehydration. Some spinal cord injury patients may sustain direct trauma to the legs; others may encounter vessel wall damage by the immobilized limbs. Shortly after injury, certain changes develop in the clotting system, especially increases in components of the von Willebrand factor macromolecular complex and increased platelet aggregability which could further contribute to hypercoagulability. Recently, an inhibition of the fibrinolytic system was suggested which also could add to a prothrombotic state. All of these interrelated processes clearly explain the high risk of venous thromboembolism in spinal cord injury patients with paralysis which has been clearly demonstrated by many investigators. It is hoped that intense thrombosis prophylaxis will reduce the incidence of this potentially devastating complication.

Publication Types: 
Review 
Review, Tutorial 

PMID: 1451539 [PubMed - indexed for MEDLINE] 

J Clin Oncol. 2003 Nov 15;21(22):4194-9.  Related Articles, Links  

  
Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism.

Goldenberg N, Kahn SR, Solymoss S.

Department of Internal Medicine, University of South Florida, Tampa, FL, USA. goldenberg.neil@tchden.org

PURPOSE: We sought to determine whether venous thromboembolism in cancer patients is associated with aberrant plasma levels of hemostatic and angiogenic factors. PATIENTS AND METHODS: Peripheral blood was collected before anticoagulant therapy from cancer patients with acute deep venous thrombosis (DVT; DVT + cancer group, n = 32), those without DVT (cancer control group, n = 36), and patients with acute DVT but no cancer (DVT control group, n = 58). Plasma assays of activation and inhibition of coagulation and fibrinolysis, as well as angiogenesis activation, were then performed. RESULTS: Median levels of thrombin-antithrombin complex, prothrombin fragments 1 + 2, and von Willebrand factor antigen were significantly greater in the DVT + cancer group than in the cancer control and DVT control groups (17.8 ng/mL v 4.6 ng/mL and 9.8 ng/mL, P =.0001 and P =.003, respectively; 3.65 nmol/L v 1.60 nmol/L and 2.71 nmol/L, P <.0001 and P =.011, respectively; and 4.04 U/mL v 2.26 U/mL and 2.06 U/mL, P <.0001, respectively). Median levels of tissue-type plasminogen activator were also significantly higher, while protein C activity was lower in the DVT + cancer group than in the DVT control group (14.6 ng/mL v 9.50 ng/mL, respectively, P =.0005; 0.89 U/mL v 1.11 U/mL, respectively, P =.0008). CONCLUSION: These data not only support prior observations of coagulation activation in patients with malignancy, but also provide new evidence for enhanced coagulation activation in the setting of acute venous thromboembolism in cancer. Future prospective studies are warranted to determine whether these and other potential markers of hypercoagulability may help to identify cancer patients at highest risk for venous thromboembolism.

PMID: 14615447 [PubMed - indexed for MEDLINE] 



