Coagulation factor V Leiden has not been detected in Japanese patients suffering from thromboses. We have performed a systematic investigation to find out genetic risk factors for thromboses in Japanese population. Routine coagulation and fibrinolysis tests were performed to determine the activities of protein S/C, antithrombin, plasminogen, heparin cofactor II and fibrinogen. Gene analyses were performed In thrombotic patients having the low activities of these factors and the constitutional background of Japanese thrombotic patients was systematically examined from the gene analyses.
Our study indicates that the frequency (19/85=0.22) of mutations of protein S gene in the Japanese patients was 5-10 times higher than that of mutations of protein S gene in Caucasian patients, and the frequency (8/85=0.09) of mutations of protein C gene was almost three times higher than that of Caucasian patients, suggesting that Protein S/Protein C Anomaly is the major risk factor for Japanese thrombophilia. It is interesting to note that the frequency of factor V Leiden (20-50%) in Caucasian deep vein thrombosis patients is similar to that (30%) of heterozygous gene mutations of the protein S/protein C anticoagulation system in Japanese deep vein thrombosis patients. Protein S_Tokushima (K155E) is another risk factor for deep vein thrombosis in Japanese population.