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    Blood coagulation factor VIII (FVIII) functions as a cofactor for activated factor IX on the phospholipid membrane in the coagulation reaction. FVIII deficiency causes hemophilia A, and conversely, the thrombotic patients show high FVIII levels. Therefore, FVIII is a key coagulant factor involved in the contradictory pathology of hemorrhage and thrombosis. From the crystal structure of the FVIII molecule and bispecific antibody that substitutes for FVIII cofactor function, FVIIIa function and role on the FXase complex are drawing attention. It has been also supported that a concept that the extrinsic coagulation system involved in the initial phase of the coagulation process, the intrinsic coagulation system involved in the thrombin burst, the anti-coagulation system by activated protein C pathway, and the fibrinolytic system involved the dissolving fibrin clot intertwine each other and progress during the coagulation reaction process. FVIII-related FVIIa coagulation system and FVIII-related plasmin regulation system have been also elucidated. We greatly expect that the developmental elucidation of thrombus formation mechanism (s) centered on FVIII/FVIIIa could lead to the development of more effective new FVIII product and antithrombotic drugs.

    Citation

    Keiji Nogami. Update on factor (F) VIII structure and function-related hemostatic coagulation and its regulatory mechanism (s)]. [Rinsho ketsueki] The Japanese journal of clinical hematology. 2021;62(7):781-789

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    PMID: 34349063

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