The role of procoagulant microparticles in haemostasis - Essay Example

Procoagulant MPs mostly appear as a result of apoptosis and vascular cell activation. An increase in the level of monocyte, platelet, or endothelial-derived MPs circulating in the blood is associated with CVD risk factors and indicates poor clinical outcome. They indicate vascular cell damage and interfere with atherothrombosis by exerting effects on vascular and blood cells. Under disease conditions, cellular cross-talk is supported by circulating MPs support, which leads to vascular inflammation, leukocyte adhesion, endothelial dysfunction, and stimulation.

Functional tissue factor and exposed membrane phosphatidyserine are procoagulant entities produced by circulating MPs. Platelet derived MPs (PMPs) contain anionic phospholipid PS, which makes them strongly procoagulant. The removal of MPs from the blood of normal human plasma prolongs the clotting time (Ahn, 2005). Platelet derived MPs support thrombin generation in plasma without platelets, which are important for blood clotting. Platelets form an important substrate for coagulation and their membranes provide a surface for the formation of prothrombinase complex.

This enzyme is utilized in the conversion of fibrinogen to fibrin which combines with other factors to form a stable clot (Lawrie et al, 2009). The availability of platelet MPs at the site of vessel injury contributes to the clotting process by providing a large surface membrane necessary for enzymatic process. The exposure of phosphotidyserine during thrombin generation increases enzymatic catalytic effect. The large surface formed by MPs is necessary for activating the coagulation cascade that forms the fibrin clot.

Circulating MPs harbor cytoplasmic effectors or functional membrane that promotes prothrombotic responses (Ay et al, 2009). These MPs channel their procoagulant potential to the target in the presence of the appropriate counter ligands. They bind onto soluble immobilized fibrinogen forming aggregates that enhance the delivery of procoagulant entities. In vitro, TF and TF-dependent procoagulant mechanism is facilitated by the interaction of monocytes and endothelial MPs. TF is a constituent protein in minute amounts that flips the endothelial procoagulant properties resulting in the initiation of a TF-driven clotting process.

Blood-borne TF can be incorporated in the developing thrombus through a series of TF-dependent, CD15 and CD18, and interactions. Blood-borne TF is mainly harbored by PMPs and monocyte-derived MPs provide the enzyme after lipopolysaccharide stimulation. Polunuclear leukocytes and endothelial-derived MPs also produce blood-borne TF under drastic endothelial activation. These MPs provide the required amount of TF and circulate the enzyme, which is necessary for maintaining a hemostatic balance. MPs, selectins and TF merge into an important triad of thrombosis.

The surfaces of platelet and endothelial cells contain an important adhesion molecule called P-selectin (Hugel et al, 2005). The molecule is utilized during TF accumulation and leukocyte inclusion in the thrombus when an endothelial injury occurs. The accumulation of hematopeic cell-derived TF is similar to the MPs accumulation kinetics before leukocyte-thrombus interaction. A soluble P-selectin enhances the production of leukocyte-derived TF-MPs used to correct hemostasis. The plasma levels of microparticles increase with age, which indicates the contribution of P-selectin pathway.

P-selectin pathway also favors the transfer of PF into monocyte derived