Hemostasis in malignancy

Abstract

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.

Should cerebral ischemic events in cancer patients be considered a manifestation of hypercoagulability?

“…9 In severe cases, administration of heparin to activate residual antithrombin III can be used; in contrast, warfarin may not be effective. 10 A similar approach might also be considered when a stroke occurs secondary to NBTE. 11 Thus, the approach to the patient with cancer who develops a stroke would be different than that for the nononcological patient if it is deemed secondary to chronic DIC/hypercoagulability.…”

Thrombocytes Are the Major Source for Soluble Vascular Endothelial Growth Factor in Peripheral Blood

“…Further investigations showed that significant concentrations of VEGF are detectable in plasma specimens upon in vivo platelet activation or intravasal platelet destruction occurs, as in autoimmune thrombocytopenia, thrombotic thrombocytopenic purpura or infection with plasmodium falciparum (manuscript in preparation). Since malignant diseases are frequently associated with a state of platelet activation, VEGF in the plasma of patients with cancer may reflect platelet activation rather than VEGF secretion by the tumor cells themselves [17]. The prognostic value of VEGF-S still remains a matter of debate.…”

Profiles of Plasma Serpins in Patients with Advanced Malignant Melanoma, Gastric Cancer and Breast Cancer

“…Nearly every type of malignant tumor has been 8 Haemostasis 1998;28:7-13 Wojtukiewicz/Ruciñska/Kloczko/Dib/ Galar reported to be associated, to a different degree, with thromboembolic complications [for review, see 1]. About 50% of all patients, and up to 95% of those with metastatic disease, show some abnormality in their hemostatic parameters [2]. Thromboembolism and hemorrhage are the second (after infection) most common cause of death in cancer patients and derive in a large proportion of cases from an imbalance between procoagulant and fibrinolytic activities [3].…”