Oral Anticoagulant Therapy

Oral anticoagulant medications impair the process of clot formation and are used to prevent thromboembolic conditions like pulmonary embolism or stroke. They can also reduce the risk of transient ischemic attacks and myocardial infarction. There are three types of oral anticoagulant medications: vitamin K antagonists, like warfarin; direct thrombin inhibitors, like dabigatran; and direct factor Xa inhibitors, like rivaroxaban.

Okay, so, the main goal of coagulation is to form a stable blood clot to stop bleeding and allow time for the tissue to be repaired. Anticoagulants work by interfering with the normal function of clotting factors involved in the coagulation cascade. Now, the coagulation cascade consists of three pathways, the extrinsic, intrinsic, and common pathways, that interact together to form a stable blood clot.

The extrinsic and intrinsic pathways both lead into the final common pathway by independently activating factor X. After factor X is activated, it becomes factor Xa, and the common pathway begins. Here, factor Xa converts prothrombin to thrombin, which then cleaves fibrinogen, into fibrin. Fibrin is a long, thin protein that ultimately creates fibrin crosslinks to form a mesh that stabilizes the clot and helps stop bleeding.

Warfarin is a vitamin K antagonist. Vitamin K supports clotting by helping produce certain clotting factors in the coagulation cascade. So as a vitamin K antagonist, warfarin impairs the synthesis of these clotting factors, and prolongs clotting time, while also depleting the functional vitamin K reserves. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct factor Xa inhibitor, both prevent the formation of fibrin. Fibrin provides strength to stabilize the clot, so without it, clot production is disrupted.

Now, the most common side effect of anticoagulants is prolonged bleeding, ranging from minor hemorrhage and localized bruising to major hemorrhage. Hypersensitivity reactions like dermatitis or urticaria can also occur. Other side effects include nausea and abdominal pain. Looking more specifically at each medication, warfarin has a Black Box warning regarding the risk of causing potentially fatal bleeding events. Both dabigatran and rivaroxaban are less likely than warfarin to cause major bleeding events. Both medications have a Black Box warning for the risk of thrombotic events if they’re discontinued prematurely. Their other side effects can include gastroesophageal reflux, esophagitis, or hemorrhagic gastritis.