CHARACTERIZATION OF 25 MONOCLONAL-ANTIBODIES TO FACTOR-VIII-VONWILLEBRAND FACTOR - RELATIONSHIP BETWEEN RISTOCETIN-INDUCED PLATELET-AGGREGATION AND PLATELET ADHERENCE TO SUBENDOTHELIUM

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 63  (6) , 1408-1415
Abstract
The role of factor VIII-von Willebrand factor (FVIII-vWF) in both platelet adherence to subendothelium and ristocetin-induced platelet aggregation was studied using monoclonal antibodies to human FVIII-vWF. Monoclonal antibodies (25) were obtained, 2 of which were directed to the factor VIII moiety of FVIII-vWF; 1 of these 2 completely inhibited the procoagulant activity (FVIII:C). The remaining 23 monoclonal antibodies were directed to the von Willebrand factor moiety of FVIII-vWF. The ability of the latter monoclonal antibodies to inhibit platelet adherence to arterial subendothelium was investigated with a perfusion model. According to the number of platelets adhering to the subendothelium, 3 groups of monoclonal antibodies could be discerned: antibodies not affecting platelet adherence; antibodies that inhibited platelet adherence to the level as observed when von Willebrand''s disease plasma was tested; and antibodies that completely inhibited both platelet adherence to subendothelium and ristocetin-induced platelet aggregation. The 2 antibodies present in group C competed for the same or closely related epitope(s) present on FVIII-vWF. A domain is present on the FVIII-vWF molecule that is associated both with ristocetin-induced aggregation and with the ability of FVIII-vWF to support platelet adherence to the subendothelium. Ristocetin-induced binding of FVIII-vWF to platelets reflects, at least in part, a physiologic mechanism regulating the function of FVIII-vWF in primary hemostasis.