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