[in Japanese]

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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.

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Background and Purpose: In order to evaluate platelet activation, we developed a simple and rapid method to detect clumps (aggregates) of platelets using a hematology analyzer. The purpose of this study is to undertake basic evaluation and to investigate the clinical usefulness of our newly modified method. Method: The measurements were done on EDTA-whole blood and citrated whole blood from patients with cerebral infarction, and from non-cerebrovascular disease (CVD) patients with or without risk factors for vascular diseases. The blood cell counts and scattergrams of platelets and white blood cells were displayed rapidly and automatically. Results: Platelet clumps were not observed in the citrated whole blood of healthy subjects. When the aggregation-inducing drugs were added to the citrated whole blood of healthy subjects, the platelets clumped dose-dependently. The appearance of platelet clumps was well correlated with ADP-induced aggregation and epinephrine-induced aggregation measured by a laser-scattering method. Aggregation was observed in 27 of 39 non-CVD patients with risk factors and 37 of 76 patients with cerebral infarction. Conclusion: The newly modified method using a hematology analyzer is useful for detecting platelet activation in vivo.

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Immunological mechanisms have been shown to be involved in heparin-induced thrombocytopenia (HIT), type II, but the mechanisms involved in HIT, type I seem to be still unknown. We previously showed that activation of platelets by mechanical stimulation such as stirring and binding of RGDS-containing proteins to the GPIIb-IIIa complex followed by their clustering are necessary for platelet aggregation in the presence of heparin in vitro. To see the effect of heparin structure on the platelet activation induced by mechanical stirring and exposure to the cold, we compared low-molecular weight heparin and two types of heparinoids: Hirudoid and danaparoid, with un-fractionated heparin. A low but significant degree of platelet aggregation was observed in the presence of low-molecular weight heparin by stirring, but not by exposure to the cold. A low but significant degree of platelet aggregation was noted in the presence of danaparoid solely under exposure of platelets to the cold. On the contrary, a significantly increased platelet aggregation was induced by Hirudoid as compared with un-fractionated heparin by both stirring and exposure to the cold. The platelet aggregation induced by Hirudoid was, however, efficiently blocked by the addition of a tetrapeptide, RGDS, as that induced by un-fractionated heparin. Thus the molecular weight and the sulfacted structure of heparin appear to play some important roles in the heparin-induced platelet aggregation.

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This article was retracted.

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