The prothrombinase complex, made up of factor Xa and factor Va, activates thrombin, a serine protease. Thrombin, once activated, proteolytically activates factors VII, XI, and VIII of the intrinsic pathway, as well as factor V and factors I and XIII of the common pathway. Hemophilia A is caused by a deficiency in factor VIII, while hemophilia B is caused by a deficiency in factor IX. Tissue factor, also known as factor III, is a glycoprotein found in the vascular endothelium and functions as an accessory protein. Primary hemostasis involves the formation of the platelet plug, while secondary hemostasis involves the formation of the fibrin meshwork. The activation of factors II, VII, IX, and X requires vitamin K for γ-carboxylation, but fibrinogen (factor I) does not. Factor V Leiden is a mutant form of factor V that is resistant to degradation by the activated protein C complex. This resistance leads to an increased risk of clot formation. Antithrombin III and protein S are proteins involved in anticoagulation. Increased production of prothrombin would result in thrombophilia, not a decreased ability. Von Willebrand factor deficiency causes a coagulopathy, affecting factor VIII and platelets. Heparin and warfarin are both anticoagulants. Heparin increases the affinity of antithrombin III for thrombin, while warfarin inhibits the regeneration of the functional form of vitamin K required for the γ-carboxylation of glutamate residues in factors II, VII, IX, and X.
Answer = D. Thrombin, a serine protease, is activated by the prothrombinase complex of factor (F)Xa + FVa. Once formed, activated thrombin (FIIa) proteolytically activates components of the extrinsic (FVII) and intrinsic (FXI, FVIII) pathways, generating FXa. Thrombin can also activate FV, FI, and FXIII of the common pathway (see figure below). Hemophilia A is caused by a deficiency in FVIII. FIX deficiency results in hemophilia B. FIII, also known as tissue factor (TF), is a transmembrane glycoprotein of the vascular endothelium. It functions as an accessory protein and not a protease. Formation of the platelet plug is primary hemostasis, and formation of the fibrin meshwork is secondary hemostasis. Vitamin K is required for the activation (γ-carboxylation) of FII, FVII, FIX, and FX (proteases that require calcium [Ca2+] and phospholipids [PL]) but not for FI (fibrinogen).
Answer = C. FV Leiden is a mutant form of FV that is resistant to proteolysis by the activated protein C complex. Decreased ability to degrade FV allows continued production of activated thrombin and leads to an increased risk of clot formation or thrombophilia. Antithrombin III (ATIII) and protein S are proteins of anticoagulation. Increased, not decreased, production of prothrombin would result in thrombophilia. Deficiency of von Willebrand factor causes a coagulopathy or a deficiency in clotting through effects on FVIII and platelets. Heparin and warfarin are anticoagulants. Heparin, a glycosaminoglycan, increases the affinity of ATIII for thrombin. Binding of ATIII removes thrombin from the blood and prevents it from converting fibrinogen to fibrin. Warfarin, a synthetic analog of vitamin K, inhibits vitamin K epoxide reductase and prevents the regeneration of the functional hydroquinone form of the vitamin that is required for the γ-carboxylation of glutamate residues to γ-carboxyglutamate (Gla) residues in FII, FVII, FIX, and FX (see figures below).