Prothrombin activation complex prothrombinase

Activated platelets provides a surface for assembly of the enzyme complexes that lead to the generation of thrombin. The prothrombinase reaction results in the enzymatic conversion of prothrombin to thrombin. Prothrombinase is a complex composed of activated factor V, activated Factor X, Ca and prothrombin (Tracy and Mann, 1986 Kane and Davie, 1988). As described in 9.3.6, these sites for assembly are also present on MPs. 

The activation of prothrombin, like that of factor X, occurs on the surface of activated platelets and requires the assembly of a prothrombinase complex, consisting of platelet anionic phospholipids, Ca, factor Va, factor Xa, and prothrombin. 

Platelet membrane phosphatidylserine is critical to the formation of the tenase complex since on its surface activated factor VIII (Villa) generates a high-afflnity binding site for activated factor IX (IXa) in the presence of calcium. Subsequently, this complex activates factor X (2, 13). Platelet membrane phosphatidylserine similarly anchors activated factor V (Va), favoring the calcium-dependent binding of activated factor X (Xa). The prothrombinase complex is generated on the surface of the anionic platelet membrane phosphatidylserine when factor Va binds prothrombin. The prothrombinase complex cleaves prothrombin to produce thrombin, which has a multifunctional role (14). 

Schematic view of the role of coagulation factor Xa in arterial thrombosis. After endothelial injury, platelets adhere to the subendothelial matrix. The procoagulant activity of the arterial clot can be attributed to the formation of the prothrombinase complex on the platelet surface which cleaves prothrombin and produces thrombin. Thrombin subsequently acts as a strong agonist of further platelet aggregation.

An important step in the blood coagulation pathway is the formation of the prothrombinase complex. The latter is a mixture of factor V, factor Xa, Ca2+, and phospholipid. In this case, a phospholipid mixture with a net negative charge will allow the prothrombinase complex to form. This active enzyme is important in cleaving prothrombin to yield thrombin. The most active phospholipid mixture for in vitro studies has proven to be phosphatidylserine-phosphatidylcholine. Subsequently the hypothesis has developed that phosphatidylserine is key to the formation of prothrombinase. 

Factor Xa and its co-factor Va form the prothrombinase complex, which activates prothrombin to thrombin. Thrombin then activates other components of the coagulation cascade, including factor V and factor VIE (which activates factor XI, in turn activating factor K), and activates factor Vni and releases it from being bound to vWF. 

The intetaction of thrombin with platelets causes increases in cytoplasnic Ca shape change and the conversion of prothrombin to thrombin via the prothrombinase complex leading to further platelet activation, aggregation and secretion. The concentration of free a-thrombin in plasma following ph)Tsiological activation has been determined to be in the range of O.S-2nM due to... 

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