Platelet prothrombinase in health and disease

Platelets play a central role in haemostasis. Not only are they involved in aggregatory and agglutination responses but they are also implicated in the clotting system. The conversion of prothrombin to thrombin, in the presence of coagulation factors Va, Xa and calcium ions, is termed prothrombinase activity. For optimal expression of this process a negatively charged phospholipid surface is required. Platelets can provide such an environment, by exposing negatively charged phospholipids at their external plasma membrane, by a 'flip-flop' process whereby negatively charged phospholipids, predominantly phosphatidylserine, move from the inner plasma membrane leaflet to the outer leaflet upon the activation of platelets by certain agonists. Such agonists include collagen and thrombin and the amount of prothrombinase activity expressed is well correlated with the propensity of the agonist to activate platelet calcium-dependent protease, calpain. This enzyme is then thought to act upon platelet cytoskeletal components, thus breaking the restraining action of the cytoskeleton upon the platelet plasma membrane and facilitating 'flip-flop'. The platelet plasma membrane is therefore a dynamic surface capable of catalytic functions in coagulation systems. Recent research has high-lighted abnormalities in platelet prothrombinase expression in certain disease states. These include Bernard-Soulier syndrome, essential thrombocythaemia and conditions where the lupus anticoagulant may be present.