UNIQUE ACTIVATION BY SHEAR STRESS OF GLYCOPROTEIN IIb/IIIa + VON WILLEBRAND (VW) FACTOR CAUSES AGGREGATION: FILTER BLOCKAGE & THE LONG BLEEDING TIME IN VW DISEASE

A filter made of fine glass fibres with tortuous capillarysized pores permitted a detailed study of the effect of varying the shearing forces by altering the pressure. Native, heparinized, citrated and EDTA blood and platelet-rich plasma were forced through the filter. Normal and VW blood were studied and the effects of antibodies to platelet glycoproteins (GPr) and of membrane-active drugs. Normally the filter blocked at 40mmHg but not at 5mmHg. At 40mmHg EM of the filter showed blockage by platelet aggregates. Initially the transit time through the filter was 8 millisecs. Platelet retention in the filter occurred in two phases: 0-3 secs required only high shear, VW factor (VWF) and GPr. IIb/IIIa. At 10-20 secs retention required high shear, VWF, GPr. IIb/IIIa and also divalent cations, and this phase only was inhibited by some membrane-active drugs. Thus VWF must act as the ligand in two different ways. It is known that ADP- or thrombin-induced aggregation requires GPr. IIb/IIIa and fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPr. IIb/IIIa and VWF. This indicates a unique method of exposing GPr. IIb/IIIa. The long bleeding time in VW disease highlights the absolute requirement for VWF and for the unique method of exposing GPr. IIb/IIIa induced by shear stress which evidently is required in normal capillary haemostasis.