Procoagulant properties of platelets

Coagulation and platelet activation have turned out to be tightly integrated processes. Thrombin, the key enzyme in the coagulation cascade, is a potent platelet agonist, acting on the platelet PAR receptors 1 and 4, and conversely, activated platelets are known to enhance and contribute to the overall coagulation process via several independent mechanisms (reviewed in [60, 61]). In this aspect, it has been found that the platelet phospholipid membrane acts as one of the main contributors to coagulation by catalyzing several enzymatic steps in the coagulation cascade. The major constituents of the platelet membrane are phosphatidycholine (PC), 38%; phosphatidylethanolamine (PE), 27%; sphingomyelin (SM), 17% and phosphatidylserine (PS), 10%. However, in the resting platelet membrane a considerable asymmetry is evident and almost no detectable PS and only 20% of the total PE is presented on the outer leaflet of the platelet surface [62]. This asymmetry is maintained by the continuous action of aminophospholipid translocase, actively transporting PS and PE to the intracellular membrane leaflet by a flip-flop mechanism [63]. The activation of the platelet will however lead to a rapid loss of asymmetry, exposing PS and more PE on the outer surface of the platelet. The mechanism is attributed to scramblase, a protein facilitating bidirectional movement of phospholipids between the two leaflets [64]. The scrambled membrane will expose a slightly anionic surface due to negative net charge of PS. Together with Ca2+ the surface efficiently binds the coagulation factor complexes and thereby increase their activity significantly (reviewed in [65]). However, the relationship between PS exposure and procoagulant activity is far from clear [66], and more research on the subject is necessary.  Another procoagulant mechanism is the concomitant release of a-granule content during platelet activation, the release resulting in a drastic increase in the local concentration of coagulation factors as well as fibrinolysis inhibitors at the site of the growing thrombus [67].