A 68-year-old man is brought to the emergency department due to sudden-onset, severe right lower extremity pain. On physical examination, the right leg is pale and cold to the touch with absent distal pulses. Cardiac auscultation reveals an irregular tachycardia, and ECG shows atrial fibrillation. Right lower extremity ultrasonography reveals an arterial embolus. Intravenous heparin infusion is initiated. This medication is most likely to cause which of the following coagulation changes?

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11ec160b_3bdc_5711_9249_6b0374c5be17_MD0001_00 Heparin is an endogenous anticoagulant that exerts its effect indirectly by binding to antithrombin III (AT), a serine protease inhibitor that irreversibly neutralizes clotting factors. Heparin binding alters the shape of AT, which converts it from a slow to rapid inactivator of clotting factors and increases its activity >1,000 fold. Although AT neutralizes a number of clotting factors in the intrinsic pathway, its anticoagulant effect primarily stems from the inactivation of factor Xa and thrombin. Therefore, patients who receive heparin products typically have the following coagulation changes: Prolonged thrombin time: Thrombin inactivation is strongest with unfractionated heparin infusion because the length of heparin chains in this formulation are longer, which inactivates thrombin more rapidly. Although low-molecular-weight heparin formulations contain shorter chain heparin molecules, they also inactivate thrombin but to a lesser extent. Decreased activity of factor Xa: All forms of heparin (eg, unfractionated, low molecular weight, fondaparinux) have strong activity against factor Xa. Antifactor Xa activity is usually monitored to determine when adequate anticoagulation is achieved. Prolonged partial thromboplastin time (PTT): Heparin primarily inhibits the intrinsic and final common clotting pathway; therefore, PTT is prolonged. Unlike heparin medications, which exert their anticoagulation effects broadly through the activation of AT, direct oral anticoagulants inhibit a single enzyme in the coagulation cascade, such as thrombin (eg, dabigatran) or factor Xa (eg, rivaroxaban). Educational objective: Heparin is an indirect anticoagulant that alters the shape of antithrombin (AT) III, thereby converting it from a slow to rapid inactivator of clotting factors. Because AT primarily neutralizes factor Xa and thrombin, patients on heparin have decreased factor Xa activity and prolonged thrombin time/partial thromboplastin time. In contrast, direct oral anticoagulants specifically target a single enzyme in the coagulation cascade, such as thrombin (eg, dabigatran) or factor Xa (eg, rivaroxaban).

A 68-Year-Old Man Is Brought to the Emergency Department Due