• Olivier Morel, Nicolas Morel, Jean-Marie Freyssinet, and Florence Toti.
• Université Louis Pasteur, Faculté de Médecine, Institut d'Hématologie et d'Immunologie, Strasbourg, F-67085 France.
• Platelets. 2008 Feb 1;19(1):9-23.

AbstractDescribed 40 years ago as cell dust, microparticles (MPs) are now considered a key component in the haemostatic response. Owing to their plasma membrane reactivity, platelets are believed to constitute the main source of circulating procoagulant microparticles and behave as true sensors for the haemostatic response. Erythrocytes, leukocytes and endothelial cells are also able to shed MPs in the blood flow, their respective contribution varying with the pathophysiologic circumstances and extent of the cellular damage. The catalytic properties of MPs rely on a procoagulant anionic phospholipid, phosphatidylserine, made accessible at the outer leaflet following plasma membrane remodelling and on the eventual presence of tissue factor (TF). Under resting conditions, most membrane-bound TF is encrypted. Although able to bind to FVIIa, it does not trigger blood coagulation. Under prothrombotic conditions, TF decryption would occur through intricate pathways involving platelets, monocytes, endothelial cells and derived MPs. P-selectin/P-selectin glycoprotein Ligand-1 (PSGL-1) interactions and reactive oxygen species would promote TF decryption in cell-MP aggregates. At sites of endothelium injury, the swift recruitment of TF+-MPs through P-selectin/PSGL-1 interactions enables the concentration of TF activity above a threshold allowing coagulation to be triggered. Another crucial feature in the initiation of blood coagulation, possibly tuned by MPs, is the balance between TF and TFPI. In specific pathophysiologic contents with elevated levels of circulating TF+-MPs, accessible TFPI at the MP surface would be overwhelmed. Beyond their procoagulant properties demonstrated in vitro, a number of pieces of evidence points to procoagulant MPs as efficient effectors in the haemostatic response, and as pathogenic markers of thrombotic disorders and vascular damage. This review will focus on the pathophysiological significance of platelet-derived MPs and their interaction with vascular cells.

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