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INTRODUCTION

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Antithrombotic therapy is used to treat acute coronary syndrome, deep venous thrombosis (DVT), pulmonary embolism (PE), 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 Myocardial Infarction and Unstable Angina,” Chapter 25, “Thromboembolism,” and Chapter 141, “Stroke and Transient Ischemic Attack.” This chapter provides an overview of antithrombotic agents.

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ORAL ANTICOAGULANTS

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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.

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Warfarin is the most commonly used oral anticoagulant in theUnited States. It preferentially inhibits 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 for 24 to 36 hours at the start of therapy. Parenteral bridging is crucial in patients with prosthetic heart valves or those who are at high risk for catastrophic complications of intravascular thrombosis when initiating warfarin. Warfarin use is contraindicated during pregnancy due to teratogenicity. Complications of warfarin use include skin necrosis (associated with protein C deficiency) and increased bleeding risk in patients with hypertension, anemia, prior cerebrovascular disease, gastrointestinal (GI) lesions, or renal disease. A number of medications, foods, or disease states interfere with warfarin absorption or metabolism and cause clinically significant consequences. There are three approaches for warfarin reversal depending on the intensity of therapy and the patient's risk for recurrent thromboembolism: stop the warfarin, administer vitamin K, and replace deficient coagulation factors. Figure 138-1 describes the management of warfarin-induced coagulopathy.

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Figure 138-1

Management of prolonged INR (warfarin-induced coagulopathy). *High risk of bleeding: age >75 years, concurrent antiplatelet drug use, polypharmacy, liver or renal disease, alcoholism, recent surgery, or trauma.There are no validated tools to predict risk of short-term major bleeding in patients with severe over-anticoagulation. The decision to admit for observation relies on physician judgment. FFP = fresh frozen plasma; IU = international unit; PCC = prothrombin complex concentrate; rFVIIa = recombinant activated factor VII.

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Direct thrombin inhibitors like dabigatran, and factor Xa inhibitors like rivaroxaban, apixaban, and edoxaban, are used in nonvalvular atrial fibrillation to reduce systemic embolism and stroke risk. A normal thrombin clotting time excludes significant coagulopathy due to dabigatran. No reversal agent ...

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