Thrombin receptor activating peptide (SFLLRN) potentiates shear-induced platelet microvesiculation

Shear-induced activation of platelets plays a major role in vascular thromb osis. Shear stress tends to increase both platelet aggregation and procoagu lant activity. One mechanism for increased procoagulant activity is promoti on of the transbilayer movement of anionic phospholipids from the inner to the outer leaflet of the platelet membrane bilayer. This is accompanied by vesiculation of the platelet membrane, resulting in the formation of procoa gulant membrane particles called microvesicles. In this study we have exami ned the effect of various platelet agonists on shear-induced platelet micro vesiculation and the development of platelet procoagulant activity, Normal citrated whole blood was subjected to laminar shear rate up to 12,500 sec(- 1) (shear stress similar to 375 dyne/cm(2)) in a cone-and-plate viscometer, and the formation of platelet microvesicles was measured by flow cytometry under different conditions. Elevated levels of shear stress induced signif icant microvesiculation. We investigated the effects of adenosine diphospha te, epinephrine, thromboxane Aa analog, collagen, and thrombin receptor act ivation peptide (SFLLRN) on shear-induced platelet microvesiculation. The t hrombin peptide significantly increased shear-induced microvesicle formatio n. In contrast, under similar conditions, the other agonists had no signifi cant effect on shear-induced microvesiculation. These studies suggest that thrombin formed in the vicinity of primary hemostatic plugs in areas of ele vated shear stress may have a major role in the propagation of thrombi by p otentiating shear-induced platelet microvesiculation.