SYSTEMIC THROMBIN GENERATION IN CANCER-PATIENTS IS CORRELATED WITH EXTRINSIC PATHWAY ACTIVATION

Since the first report by Trousseau in 1865, several experimental and clinical studies have established that activation of coagulation is co mmon in cancer. However, the biochemical basis of the activation of co agulation in cancer patients is still not completely understood. The c urrent most accepted opinion is that initiation of coagulation in mali gnancy is driven primarily by activation of the extrinsic (tissue fact or-dependent) pathway. In order to further prove that such a pathogene tic mechanism is actually involved in cancer patients, we correlated t he plasma levels of activated factor VIIa (FVIIa), which represent a v ery small fraction of plasma FVII, with some well-established markers of systemic thrombin generation. Circulating FVIIa was measured using a prothrombin time-based assay that employs a truncated form of human recombinant tissue factor, while plasma levels of the thrombin-antithr ombin complex, the prothrombin fragments 1 + 2 and D-dimer were determ ined by commercially available ELISA kits. The study was carried out i n 37 patients with different types of cancer and 20 healthy controls. Plasma levels of FVIIa were significantly increased while those of FVI I antigen (FVIIag) were decreased in cancer patients compared with con trols. Furthermore, the FVIIa/VIIag ratio was more than two-fold highe r in cancer patients than in controls. In addition, an excess of throm bin generation was observed in cancer patients. Interestingly, a posit ive correlation between the FVIIa/VIIag ratio and the plasma levels of either D-dimer (Spearman's r = 0.325; P = 0.027) or prothrombin fragm ents 1 + 2 (r = 0.309; P = 0.034) was observed in cancer patients. In conclusion, our study further supports the hypothesis that the tissue factor/VIIa complex is the main determinant of coagulation activation in cancer patients. Large clinical studies will be necessary to determ ine whether FVIIa and the FVIIa/VIIag ratio are useful prognostic fact ors of thromboembolic events in cancer patients. (C) 1998 Rapid Scienc e Ltd.