Prothrombin activation complex

The first and most completely characterized of the activation complexes of the procoagulant subsystem is that of prothrombin activation. Because of this, the prothrombin activation complex will be described in greater detail than the other, similar activation complexes (Figure 36-9) The general principles described below apply to all of the complexes. 

IRacy PB, Mann KG. Amodel for assembly of coagulation factor complexes on cell surfaces Prothrombin activation on piatdets. In Btodiemistry of Plaldets. Eds DR Phillips and MA Shuman, Academic (Orlando), pp 296,1986. 

B4. Bauer, K. A., Teitel, J. M., and Rosenberg, R D., Assays for the quantitation < antitfarombin 111 thrombin-antithrombin complex and prothrombin activation fragments. In Disorders of Thrombin Formation (R W. Colman, ed.), pp. 142-155. Churchill-Ljvingstone, Edinburgh and London, 1983. 

The interaction of heparin with human plasma low-density lipoprotein has been studied by gel permeation chromatography A fraction containing degradation products of fibrinogen formed in blood plasma after injection of thrombin also contains a complex of fibrinogen and heparin. The rate of inactivation of thrombin and Factor by anti-thrombin has been shown to be directly proportional to the chain-length of heparin.The effects of heparin on the reactions catalysed by Factor have been examined.Heparin inhibits the ability of phospholipid to accelerate prothrombin activation in a mechanism which appears to involve the displacement of Factor X from the surface of the phospholipid. 

Lipids play an essential role in both the intrinsic and extrinsic pathways of proArombin activation. They enter the coagulation sequence after it has been initiated by surface contact and other protein interactions. There is no evidence that they initiate the coagulation process. The lipid is normally derived from the blood platelet where it probably exists as lipoprotein. It exerts a surface catalytic action on the plasma coagulation proteins with which it may bind in the presence of calciiun. The resulting complex could contain platelet liproprotein or its lipid moiety alone and may mediate prothrombin activation. 

Initiation of the fibrin clot in response to tissue injury is carried out by the extrinsic pathway. How the intrinsic pathway is activated in vivo is unclear, but it involves a negatively charged surface. The intrinsic and extrinsic pathways converge in a final common path-vray involving the activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen to form the fibrin clot. The intrinsic, extrinsic, and final common pathways are complex and involve many different proteins (Figure 51-1 and Table 51-1). In... 

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. 

APCC, activated prothrombin complex concentrate PCC, prothrombin complex concentrate vWF, von Willebrand factor. 

Treatment algorithm for the management of patients with hemophilia A and factor VIII antibodies. BU, Bethesda unit PCC, prothrombin complex concentrate a PCC, activated prothrombin complex concentrate. 

There is discussion on the adequacy of tests to identify the hypercoagulable states underlying susceptibility to VTED. The complexity of factors and interactions involved in the hemostatic equilibrium has favored the use of functional tests. Among the several options available the measurement of fragments 1 + 2 (F1 + 2), the amino terminus fragment split during the activation of prothrombin has been widely considered the test of choice. The sparse information available for SERMs, however, is unclear. Raloxifene did not modify... 

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). 

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