ABNORMALITIES OF BLOOD-COAGULATION IN PATIENTS WITH CANCER - MONONUCLEAR CELL TISSUE FACTOR GENERATION

Abstract

Activation of blood coagulation as characterized by the occurrence of disseminated i.v. coagulation, increased levels of plasma FPA [fibrinopeptide A] and the local deposition of fibrin are common in experimental animals and patients with malignant tumors. Many mechanisms have been proposed for the mediation of this response to tumors, including tumor-associated proteases, platelet adherence to tumors, surface activation of blood coagulation by tumor cells and activation of coagulation by tissue factor derived from either tumor tissue or reactive leukocytes. The hypothesis that MTF [monocyte tissue factor] generation may contribute to increased fibrin generation in cancer patients was investigated. Plasma FPA levels and in vitro unstimulated MTF generation were measured simultaneously in samples obtained from 35 patients with lung cancer. FPA levels were significantly elevated in these patients as compared to a group of 20 normal volunteers (P = 0.03). Although unstimulated MTF generation showed considerable variability in the patients and the normal volunteers, a high degree of correlation was observed between simultaneous levels of FPA and MTF regardless of whether MTF was expressed per cell (r = 0.83), per monocyte (r = 0.95) or per volume of peripheral blood (r = 0.96). MTF generation was also significantly decreased in a group of patients receiving sodium warfarin (P < 0.001). MTF generation may have a role in the activation of blood coagulation in neoplasia and inhibition of MTF generation by war farin may be partially responsible for the decreased FPA values previously reported in anticoagulated cancer patients.