Shear stress activation of platelet glycoprotein IIb/IIIa

Abstract

When normal native or heparinised blood is forced under pressure through a filter with capillary sized holes, platelets aggregate during their passage through the filter which takes 8 ms. When sufficient aggregates are retained the filter blocks. The effluent blood is collected from 0–3s (first phase) and between 10–20s (second phase); the platelets are counted, and the percentage retained is calculated. Normally this is 50±12% and 66±15% respectively. With von Willebrand’s (vW) blood no blocking occurs and platelet retention in both phases is low. With EDTA blood and in the presence of some “membrane active” drugs, the first phase is normal; retention during the second phase is, however, decreased with no blocking. The use of monoclonal antibodies shows that glycoproteins (GP) IIb/IIIa and vWf are essential for blocking, but GP Ib is not. Thus, aggregation in the first phase requires high shear, vWf and GP IIb/IIIa only, while divalent cations are essential for the second. It is proposed that high shear alone will expose and activate GPr IIb/IIIa; vWf is then essential for platelet aggregation in the filter and fibrinogen is largely irrelevant.