Procoagulant expression in platelets and defects leading to clinical disorders

Hemostasis is a result of interactions between fibrillar structures in the damaged vessel wall, soluble components in plasma, and cellular elements in blood represented mainly by platelets and platelet-derived material. Durin g formation of a platelet plug at the damaged vessel wall, factors IXa and VIIIa form the "tenase" complex, leading to activation of factor X on the s urface of activated platelets. Subsequently, factors Xa and Va form the "pr othrombinase" complex? which catalyzes the formation of thrombin from proth rombin, leading to fibrin formation. An enhanced expression of negatively c harged phosphatidylserine in the outer membrane leaflet resulting from a br eakdown of the phospholipid asymmetry is essential for the formation of the procoagulant surface. An ATP-driven and inward-acting aminophospholipid "t ranslocase" and a "floppase" counterbalancing this have been postulated to maintain the dynamic state of phospholipid asymmetry, A phospholipid-nonspe cific "scramblase," believed to be responsible for the fast breakdown of th e asymmetry during cell activation, has recently been isolated from erythro cytes, cloned, and characterized. An intracellular calcium-binding segment and one or more thioesterified fatty acids are probably of importance for c alcium-induced activation of this transporter protein, Cytosolic calcium io ns also activate the calcium-dependent protease calpain associated with she dding of microvesicles from the transformed platelet membrane. These are sh ed with a procoagulant surface and with surface-exposed P-selectin from the alpha-granules. Theoretically, therefore, microvesicles can be involved in both coagulation and inflammation. Scott syndrome is probably caused by a defect in the activation of an otherwise normal scramblase, resulting in a relatively severe bleeding tendency. In Stormorken syndrome, the patients d emonstrate a spontaneous surface expression of aminophospholipids. Activate d platelets and the presence of procoagulant microvesicles have been demons trated in several clinical conditions, such as thrombotic and idiopathic th rombocytopenia, disseminated intravascular coagulation, and HIV-1 infection , and have been found to be associated with fibrin in thrombosis, Procoagul ant microvesicles may also be formed from other cells as a result of apopto sis.