PLATELET-DERIVED MICROPARTICLES ASSOCIATE WITH FIBRIN DURING THROMBOSIS

Platelet-derived microparticles (MP) are reported to express both pro- and anticoagulant activities. Nevertheless, their functional signific ance has remained unresolved. The present study monitored the generati on and fate of MP in an experimental model of thrombosis with costimul ation of platelets by collagen and thrombin. When minimally anticoagul ated (0.5 mu mol/L PPACK) blood was perfused over immobilized fibrilla r type I collagen in a flow chamber at a low shear rate (300 s(-1)), e ndogenous thrombin was generated, as evidenced by thrombin-antithrombi n III complex. In contrast to full anticoagulation (50 mu mol/L PPACK) and the ab sence of collagen, large platelet aggregates and fibrin en sued during perfusions over collagen in the presence of thrombin. In t hese thrombi, MP, defined as GPIIbIIIa- and P-selectin-positive vesicl es (<1 mu m), were found to align fibrin in immunofluorescence and sca nning immunoelectron microscopy. Moreover, in sections of embolectomiz ed thromboemboli from patients GPIIbIIa- and P-selectin-positive mater ial compatible with MP was detected in a fibrin strand-like pattern. I n vitro binding studies showed that MP bound to fibrin and acted there as procoagulants. In summary, we show that MP generated during thromb us formation associate with local fibrin. This adhesive function fibri n could imply a sustained modulatory role for MP in evolving thrombi. (C) 1996 by The American Society of Hematology.