Chapter 88: Principles of Antithrombotic and Antifibrinolytic Therapy

INTRODUCTION

• Antithrombotic agents are characterized separately as anticoagulants (including vitamin K antagonists, heparin or heparin derivatives, and directly acting thrombin or factor Xa inhibitors), antiplatelet agents, or fibrinolytic drugs (see Chap. 87), depending on their primary mechanism, although there is overlap in their activities. Table 88–1 provides an overview of the types of the most frequently used anticoagulant, antiplatelet, and fibrinolytic agents.

• Anticoagulant therapy acts to decrease fibrin formation by inhibiting the formation and action of thrombin. Its most common use is in preventing systemic embolization in patients with atrial fibrillation, treatment of acute arterial thrombosis (eg, myocardial infarction or peripheral arterial thrombosis), and 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 (Table 88–2). 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, new oral anticoagulants with specific antithrombin activity or anti–factor Xa activity have become available and are currently increasingly used (see section, “Oral Antithrombin and Anti–Factor Xa Agents” below).

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 ...