Shear-induced platelet activation and platelet microparticle formation in native human blood

Shear-induced platelet activation and platelet microparticle formation are triggered in native human blood by high arterial shear or by a sudden incre ase in shear as introduced by a stenosis with potential consequences for co llagen-induced platelet thrombus formation. Blood was drawn from healthy vo lunteers and directly perfused ex vivo over various well-defined eccentric stenoses. Shear-induced platelet activation was determined by using flow cy tometry to assess: 1) GPIIb-IIIa activation by fluorescein isothiocyanate ( FITC)-labeled Mab PAC-1; and 2) translocation of membrane aminophospholipid s (procoagulant activity) by FITC-labeled Annexin V. Microparticle formatio n was measured by flow cytometry and FITC-labeled Mab Y2/51 directed agains t GPIIIa. Significant platelet activation and platelet microparticle format ion were elicited when the wall shear rate reached 10,500 sec(-1) for a per iod of 0.075 sec. Prolonged exposure to or a rapid increase in shear furthe r enhanced activation and microparticle formation. Shear-induced platelet a ctivation was associated with significantly increased collagen-induced plat elet thrombus formation that was insensitive to aspirin ingestion. Exposure of native blood to very high shear thus activates platelets to express GPI Ib-IIIa, renders the platelet membrane procoagulant and stimulates micropar ticle formation. These responses are associated with enhanced collagen-indu ced thrombus formation by prostaglandin-independent mechanisms. (C) 1998 El sevier Science Ltd.