The Role of Hemostatic System Inhibitors in Malignancy

ABSTRACT

Malignancy is associated with alterations in the hemostatic system that present as thromboembolic or bleeding complications. Antineoplastic treatment further escalates blood coagulation and fibrinolytic abnormalities. Moreover, hemostatic system inhibitors play a role in tissue maintenance or, contrarily, contribute to cancer progression. The inhibitors regulate migration, proliferation, apoptosis, angiogenesis, and distant metastases formation, as well as interfere with host defense system mechanisms. They exhibit different functions depending on tumor type, histologic grade, and clinical stage of the disease. The activity of coagulation inhibitors underlies the pathomechanisms of some complications resulting from therapeutic procedures, such as radiation injury to normal tissues. Because coagulation activation is widely recognized to influence cancer growth and distant dissemination, numerous attempts were made to introduce various forms of coagulation inhibitors to antineoplastic treatment. This review summarizes up-to-date information on preclinical and clinical benefits and pitfalls of hemostatic system inhibitors administration in cancer, with special emphasis on tumor biology and prophylaxis and treatment of various complications observed in the course of malignant disease.

KEYWORDS

Hemostatic system inhibitors - cancer - TFPI - TFPI-2 - AT III - protein C system - protein Z - ZPI - fibrinolysis inhibitors - heparin

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