Shear Rate Dependent Inhibition of Platelet Adhesion and Aggregation on Collagenous Surfaces by Antibodies to Human Factor VIII/von Willebrand Factor

Abstract

The effect of heterologous and homologous antibodies to factor [F] VIII/von Willebrand factor (FVIII/VWF) and purified VWF on the interaction of human platelets with subendothelium and with a surface consisting of collagen fibrils was investigated using annular flow chambers. Wall shear rates of 200-5200 s-1 were produced by varying the flow rate of the citrated blood which was circulated through these chambers by a pump. Surface coverage with platelets and with platelet aggregates was measured morphometrically. The antibodies had no effect on platelet adhesion at low shear rates. An increasing inhibition of adhesion was observed with increasing shear rates. The antibodies to FVIII/VWF and to purified VWF virtually abolished adhesion at shear rates present in the microvasculature (1300-5200 s-1). Antibodies to FVIII:C which were isolated from 2 patients with hemophilia A had no effect on adhesion. Antibodies to FVIII/VWF and purified VWF inhibited adhesion-induced aggregation. FVIII/VWF plays an essential role as cofactor for platelet adhesion to subendothelium and collagen fibrils at high blood shear rates, i.e., when the time available for establishment of a stable bond between platelets and collagenous surfaces is short.