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This topic analyzes the biochemistry of the coagulation cascade, specifically clotting factors and their biochemical interactions and roles among cell membranes, platelets, proteases, and cofactors. Other components involved in clot formation should be referenced, but the focus should be on clotting factors. The coagulation cascade is a well-studied and pertinent topic for health professionals to understand. Although this topic does not cover the coagulation cascade and its role in hemostasis as a simple chain of events, a brief overview should be included. A thorough examination of these biochemical interactions illuminates the coagulation cascade's underlying intricacies, enabling a seamless cohesive process.

Here, commonly tested areas regarding the pathophysiology of clotting factors is discussed. Hemophilias Hemophilia A is an X-linked recessive coagulopathy that results in dysfunctional VIII. From our earlier discussion, we can see how dysfunctional VIII result in coagulopathy and prolonged PTT. Patients with this disorder often present with easy bruising, bleeding after dental procedures or from operations in general, and hemarthrosis. Hemophilia A can be treated with desmopressin and recombinant factor VIII. Desmopressin causes endothelial cells to release vWF, which stabilizes VIII. Hemophilia B, sometimes called Christmas disease, is an X-linked recessive coagulopathy resulting in dysfunction of IX. As with hemophilia A, hemophilia B also cause a prolonged PTT. The difference is hemophilia A is a cofactor deficiency while hemophilia B is a protease deficiency; therefore, desmopressin not be a good treatment option as these patients require recombinant factor IX. Hemophilia B present with the same symptoms as hemophilia A. It is important to note that hemophilia A and B have a normal prothrombin/INR. Von Willebrand Disease Von Willebrand disease (vWD) is the most commonly inherited coagulopathy. vWD can be differentiated from hemophilias in several ways. First, the vWF mode of inheritance is autosomal dominant. Secondly, vWD is a disease of platelet dysfunction and manifest primarily as mucosal membrane bleeding, such as epistaxis and prolonged menstrual cycles. Thirdly, bleeding time is normal in hemophilia, whereas it is prolonged in vWD. Since vWF increases the half-life of VIII, one can also expect to see a prolonged PTT in this disorder. Desmopressin can be used as a treatment option; however, certain subtypes of vWD do not warrant this treatment option. Vitamin K Deficiency Previously, we discussed the importance of vitamin K and its clotting factors II, VII, IX, X, protein C, and S. The effects of vitamin K deficiency can be observed in both the extrinsic and intrinsic pathways and directly measured via prothrombin time and PTT, which be prolonged. The etiology of vitamin K deficiency is extensive but commonly arises on test questions regarding patients with poor diet, pancreatic insufficiency, liver disease, intestinal flora imbalances, neonates, or mimicked by patients on warfarin therapy. Warfarin

Previously, we discussed the importance of vitamin K and its clotting factors II, VII, IX, X, protein C, and S. The effects of vitamin K deficiency can be observed in both the extrinsic and intrinsic pathways and directly measured via prothrombin time and PTT, which be prolonged. The etiology of vitamin K deficiency is extensive but commonly arises on test questions regarding patients with poor diet, pancreatic insufficiency, liver disease, intestinal flora imbalances, neonates, or mimicked by patients on warfarin therapy. Warfarin Vitamin K assists in the carboxylation of clotting factors II, VII, IX, X, protein C, and S. The enzyme responsible for gamma-carboxylation is vitamin K epoxide reductase, which is inhibited by warfarin. As mentioned previously, patients on warfarin have the coagulation status measured via INR. In emergency clinical settings, warfarin’s therapeutic effects are negated by the administration of fresh frozen plasma. In a less urgent clinical setting, patients may be administered vitamin K. Rarely; patients may experience warfarin-induced skin necrosis within the first few days of beginning warfarin. This is because protein C has the shortest half-life of vitamin K-dependent clotting factors; therefore, a patient enters a prothrombotic state. However, this rare complication is more common in patients with protein C deficiency. To help eliminate this complication, patients are often co-administered heparin while beginning warfarin therapy as heparin’s onset is immediate while warfarin’s onset takes 2 to 3 days.