Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ INTRODUCTION ++ Antithrombotic agents are characterized separately as anticoagulants (including vitamin K antagonists and heparin or heparin derivatives), antiplatelet agents, or fibrinolytic drugs (see Chap. 87), depending on their primary mechanism, although there is overlap in their activities. Anticoagulant therapy acts to decrease fibrin formation by inhibiting the formation and action of thrombin, and its most common use is in preventing systemic embolization in patients with atrial fibrillation, treatment of acute arterial thrombosis (e.g., myocardial infarction or peripheral arterial thrombosis) and for treatment or (secondary) prevention of venous thromboembolism. Anticoagulant therapy is often monitored using coagulation testing because of marked biologic variation in effect. Antiplatelet agents act to inhibit platelet function, and their primary uses are in preventing thrombotic complications of cerebrovascular and coronary artery disease. They also have a role in treatment of acute myocardial infarction. They have no effect in preventing or treating venous thromboembolism. For many agents, the risk-to-benefit ratio is narrow, with the result that bleeding complications occur. Bleeding is the most common adverse effect of anticoagulation (see Table 88–1). Consequently, the clinician should carefully weigh the risks and benefits for each patient when selecting treatment. The most common oral anticoagulants are vitamin K antagonists (coumarins). However, recently, new oral anticoagulants with specific antithrombin activity or anti-factor Xa activity have become available and are currently evaluated in clinical trials (see section, "Oral Antithrombin and Anti-factor Xa Agents" below). ++Table Graphic Jump LocationTABLE 88–1RISK FACTORS FOR HEMORRHAGIC COMPLICATIONSView Table|Favorite Table|Download (.pdf) TABLE 88–1 RISK FACTORS FOR HEMORRHAGIC COMPLICATIONS Too high intensity of anticoagulation Simultaneous use of anticoagulants and antiplatelet agents Old age Initial phase of anticoagulation Cerebrovascular disease History of alcohol abuse Renal insufficiency Liver failure Use of nonsteroidal antiinflammatory drugs (gastrointestinal bleeding) Polymorphisms in cytochrome 450 CYP2C9 gene ++ VITAMIN K ANTAGONISTS ++ Coumarins act by inhibiting vitamin K–dependent posttranslational γ-carboxylation of glutamic acid residues in the Gla domains of coagulation factors II, VII, IX, and X, and the anticoagulant proteins C and S. γ-Carboxylation requires the reduced form of vitamin K as a cofactor. During γ-carboxylation, vitamin K is oxidized. The enzymes, vitamin K epoxide reductase and vitamin K reductase, are required to recycle vitamin K back to its reduced form. Coumarins inhibit these reductases, thus depleting reduced vitamin K. A decrease in the number of γ-carboxyglutamate residues results in coagulation factors with impaired activity because they are unable to bind calcium and undergo necessary conformation changes. The production of affected coagulation factors stops promptly, but the anticoagulant effect is delayed until the previously formed coagulation factors are removed from the circulation. Factor VII has the shortest half-life at 6 hours, while the others range from 24 to 72 hours. ++ Pharmacokinetics ++ Warfarin, the most commonly used coumarin, has predictable oral absorption and a half-life of 35 to 45 hours. The pharmacokinetics appear to be ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!