Drugs that Affect Hemostasis

A well-regulated hemodynamic system keeps blood fluid and clot-free in normal vessels and forms a localized clot rapidly in injured vessels.⁹ The first step in the formation of a localized clot at the site of vessel injury is vasoconstriction. This is followed by platelet aggregation and the formation of a primary hemostatic plug. Secondary hemostasis, also known as the coagulation cascade, leads to the formation of a stable, permanent clot. An abnormal extension of hemostasis is thrombosis.⁹

Thrombosis is characterized by the uncontrolled enlargement of clots that occlude blood vessels as a result of (1) injury of the endothelium associated with hyperlipidemia and hypertension; (2) abnormal blood flow, i.e. turbulence or stasis associated with atherosclerosis, arrhythmias, valvular problems, and heart failure, and (3) genetic or acquired hypercoagulability.⁹ Drugs in the top 300 that affect hemostasis (Table 5) fall into two major categories: antiplatelet agents and anticoagulants.^2,9,10

Table 5. Drugs that Affect Hemostasis and Thrombosis.^2,^9,¹⁰

Drugs*	Mechanisms of Action	Common Indications
Class IC antiarrhythmics Flecainide	Block voltage-gated Na+ channels in ventricular myocytes	Sustained ventricular tachycardia Paroxysmal supraventricular tachycardia Paroxysmal atrial fibrillation
Cyclooxygenase inhibitors Aspirin	Inhibit platelet cyclooxygenase, thereby Block thromboxane A₂-dependent platelet aggregation	Prophylaxis against Transient ischemic attacks Myocardial infarction Thromboembolic disorders Reocclusion in coronary revascularization procedures and stent implantation
ADP receptor pathway inhibitors Clopidogrel	Block platelet ADP receptors thereby Inhibit ADP-dependent platelet activation	Secondary prevention of atherosclerotic events in patients with recent MI, stroke, or peripheral vascular disease Acute coronary syndromes Prevention of stent thrombosis in combination with aspirin
Traditional anticoagulants Warfarin	Inhibit hepatic peroxide reductase that catalyzes the regeneration of reduced vitamin K, which is required for the synthesis of biologically active coagulation factors II, VII, IX, and X	Prophylaxis and treatment Pulmonary embolism Deep vein thrombosis Systemic embolism Post-MI Atrial fibrillation Rheumatic HD with valve damage Prosthetic heart valve
Selective Factor Xa inhibitors Rivaroxaban Apixaban	Competitively inhibit factor Xa by binding to the active side on the enzyme	Prevention Thromboembolism with atrial fibrillation Prevention and treatment Deep vein thrombosis Pulmonary embolism
Direct thrombin inhibitors Dabigatran	Bind directly to thrombin and thereby inhibit secondary hemostasis	Prevention Thromboembolism with atrial fibrillation Treatment Deep vein thrombosis Pulmonary embolism

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