Antithrombotic therapy is used to treat ST elevation MI, non-ST elevation MI, unstable angina, deep venous thrombosis, pulmonary embolism, transient ischemic attack, and ischemic stroke. These agents are also used to prevent occlusive vascular events in patients at risk. Detailed management strategies and dosing regimens are provided in Chapter 18 "Acute Coronary Syndromes: Management of Acute Myocardial Infarction and Unstable Angina," Chapter 25 "Thromboembolism," and Chapter 141 "Stroke and Transient Ischemic Attack." This chapter provides an overview of antithrombotic agents.
The goals of anticoagulant therapy include (1) stop further acute thrombosis, (2) reduce the risk of embolism from a thrombus, and (3) prevent the formation of de novo thrombus in patients at risk.
Warfarin is the most commonly used oral anticoagulant in the United States. It works by preferentially inhibiting vitamin K dependent cofactors in the extrinsic coagulation cascade. Dosing is guided by measuring the international normalized ratio (INR), and most patients are therapeutic in a range of 2 to 3. Patients with mechanical heart valves or antiphospholipid antibody syndrome require an INR of 2.5 to 3.5. It takes about 3 to 4 days to reach full anticoagulation upon initiating treatment. A parenteral anticoagulant should be used until the INR is maintained in the desired range for 2 days as warfarin therapy causes a transient state of thrombogenesis at the start of therapy. A number of medications, foods, or disease states interfere with warfarin absorption or metabolism and cause clinically significant consequences. Warfarin use is contraindicated during pregnancy due to teratogenicity. Complications of warfarin use include bleeding from over-anticoagulation, increased bleeding risk in patients with hypertension, anemia, prior cerebrovascular disease, GI lesions, and renal disease. Skin necrosis is associated with protein C deficiency. Figure 138-1 describes the management of warfarin-induced coagulopathy.
Algorithm for management of warfarin-induced coagulopathy.
*High risk of bleeding: age >75 years, concurrent antiplatelet drug use, polypharmacy, liver or renal disease, alcoholism, recent surgery, or trauma. FFP = fresh frozen plasma; INR = international normalized ratio.
Dabigatran is currently the only available oral direct thrombin inhibitor in the United States. It requires no laboratory monitoring. No reversal agent is available and long-term safety has not been established. Rivaroxaban, a direct Factor Xa inhibitor, is available in Europe and Canada.
Parenteral agents include unfractionated heparin (UFH), low molecular weight heparin (LMWH) (eg, enoxaparin, dalteparin), Xa inhibitors (fondaparinux), and direct thrombin inhibitors (eg, bivalirudin, lepirudin, argatroban). UFH and LMWH are used to treat and prevent deep vein thrombosis, as well as pulmonary embolism (PE), unstable angina, and acute myocardial infarction. Enoxaparin 1 milligram/kilogram SC every 12 hours may be used in outpatient management of DVT. Dosing regimens for UFH and LMWH are weight based. UFH requires monitoring of the activated ...