Cell-Derived Microparticles Generated in Patients During Cardiopulmonary Bypass Are Highly Procoagulant

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Abstract
Background Microparticles from platelets and other cells have been extensively studied and characterized in vitro. Although the level of platelet-derived microparticles is elevated in a variety of diseases, including cardiac surgery, virtually nothing is known about their functions in vivo. The aim of the present study was to investigate the procoagulant properties of microparticles generated in vivo. Methods and Results In 6 patients at the end of cardiopulmonary bypass, 14.8×10 9 /L (median; range, 9.7 to 27.4×10 9 /L) platelet-derived microparticles were present in pericardial blood, whereas blood obtained from the systemic circulation contained 1.6×10 9 /L (median; range, 0.4 to 8.9×10 9 /L) of such microparticles, as determined by flow cytometry. Microparticles stained positively for phosphatidylserine as determined with labeled annexin V. In contrast to systemic blood, pericardial blood contained not only microparticles of platelet origin but also microparticles that originated from erythrocytes, monocytes, or granulocytes, and other hitherto unknown cellular sources. Plasma prepared from pericardial blood and to a lesser extent plasma from systemic blood obtained at the same time, stimulated formation of thrombin in vitro. This activity of pericardial plasma was lost after removal of its microparticles by high-speed centrifugation, whereas the corresponding microparticle pellet was strongly procoagulant. The generation of thrombin in vitro involved a tissue factor/factor VII–dependent and factor XII–independent pathway. Conclusions This study is the first to demonstrate that microparticles generated in vivo can stimulate coagulation.