[Role of newly developed technology in blood coagulation disorders].

Clarification of blood coagulation disorders has been made progress based on newly developed technologies. ANTITHROMBIN III: In 1979, studies were carried out on antithrombin III(AT III) as a blood coagulation inhibitor from the first Japanese case of congenital AT III deficiency found in the laboratory sample. An alternative anticoagulant to maintain fluidity in extracorporeal circuit in an AT III deficient patient requiring hemodialysis was needed. In 1989, it was firstly introduced argatroban, a synthetic thrombin inhibitor as an alternative anticoagulant instead of human antithrombin III concentrate plus heparin regimen during hemodialysis. In 1992, success of good delivery in pregnant woman with an AT III deficiency was obtained to maintain normal level of AT III by the concentrates. DYSFIBRINOGENEMIA: Two families of congenital dysfibrinogenemia in clue to abnormally high levels of serum fibrinogen degradation products(FDP) were found. Polymerization detect due to dysfibrinogenemia induced high level of serum FDP and normal level of fibrin d-dimer products. HEPARIN COFACTOR II DEFICIENCY: A patient with congenital heparin cofactor II(HCII) deficiency was found in clue to four episodes of repeated restenosis under heparin-anticoagulated coronary angioplasty. For preventing the restenosis, argatroban as an alternative of heparin was used during coronary angioplasty. No restenosis after the angioplasty was appeared in anticoagulation with argatroban. Genetic analysis of the HCII was described that gene protein is secreted normally, but rapidly degraded in the circulation. FACTOR VII: In Japanese elderly, increase of Factor VII clotting activity was found to relate to high risk of cardiovascular disease. Elevation of activated FVII(FVIIa) as an activation marker of FVII in cardiovascular disease indicates to be an independent risk factor for cardiovascular disease. HEPARIN INDUCED THROMBOCYTOPENIA: HIT: HIT is believed to be less frequent in Japanese because of lack of recognition due to poor understanding of HIT's paradox. A survey in Japanese indicated to be no less frequent compared with that of the West. A causativity for HIT has been identified as antibodies against PF4/heparin complexes. As detection of the antibodies can easily be done by ELISA test, the test is desirable to become popular. Treatment for HIT is recommended to stop heparin and start a thrombin inhibitor. In Japan, argatroban and nafamostat mesilate are selected as an alternative agent for HIT, but both drugs have no approval for Japanese HIT patients.