Chapter 239: Thrombotics and Antithrombotics

INTRODUCTION

Antithrombotic therapy (i.e., anticoagulants, antiplatelet agents, and fibrinolytics) is used to treat arterial and venous thromboembolic conditions, including acute coronary syndrome, deep venous thrombosis, pulmonary embolism, transient ischemic attack, and ischemic stroke. Moreover, antithrombotic agents help prevent occlusive vascular events in patients at risk for thrombosis due to atherosclerotic arterial disease, atrial fibrillation, medical illness with immobility, or surgical insult. These agents, however, can cause life-threatening complications, primarily serious hemorrhage. Detailed management strategies for thromboembolic disorders are discussed in their respective chapters (see chapter 49, "Acute Coronary Syndromes"; chapter 56, "Venous Thromboembolism"; and chapter 167, "Stroke Syndromes").

Hemostasis—whether physiologic after accidental injury or pathologic after rupture of an atherosclerotic plaque—is initiated by platelet interaction with the vascular subendothelium and continues with a series of reactions among plasma coagulation proteins that generate the final product of cross-linked fibrin incorporated into the initial platelet plug (see chapter 232, "Tests of Hemostasis"). Arterial thrombi, composed primarily of platelets bound by thin fibrin strands, develop under high-flow conditions, especially at sites of ruptured plaques. Both anticoagulants and platelet-inhibiting drugs may effectively prevent and treat arterial thrombosis. In contrast, venous thrombi form in areas of sluggish blood flow and are composed mainly of red blood cells and large fibrin strands. Anticoagulant drugs are more effective than antiplatelet drugs in preventing venous thromboembolism.

Antithrombotic agents are classified by their mechanism of action. Anticoagulants block the synthesis or activation of clotting factors, interfering with the coagulation cascade at one or more steps. Antiplatelet agents interfere with platelet activation or aggregation. Fibrinolytic agents (often but inaccurately referred to as thrombolytic agents) stimulate the enzymatic dissolution of the fibrin component.

Thrombotic agents are used to diminish bleeding due to either an anithrombotic agent or and acquired or genetic bleeding disorder (see chapters 233 and 235, "Acquired Bleeding Disorders" and "Hemophilias and von Willebrand's Disease", respectively).

ORAL ANTICOAGULANTS

Oral anticoagulants are used to (1) stop further thrombosis when the condition already exists (e.g., venous thrombosis), (2) reduce the risk of embolism in patients with thrombotic disease (e.g., venous thrombosis or left ventricular mural thrombus), and (3) prevent thrombi from forming in patients with risk factors for their development (e.g., atrial fibrillation, prolonged immobilization, or prosthetic heart valve) (Table 239–1).