Anticoagulants and Transaminase Elevation

Abstract

Case 1: Mr F., a 65-year-old man with hypertension and atrial fibrillation, began long-term anticoagulation with warfarin 1 year ago. He presented with a 1-week history of nausea, anorexia, jaundice, and altered mental status. His laboratory workup showed elevated serum transaminases and direct bilirubin. Could warfarin be potentially responsible? Case 2: Mr S., a 75-year-old man with diabetes and coronary artery disease, presented with an acute anterior myocardial infarction. Echocardiography showed a left ventricular aneurysm with apical akinesis and thrombus. He was started on enoxaparin, and 3 days later, he developed a rise in alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN). Could this laboratory abnormality be related to enoxaparin? Drug-induced hepatotoxicity is the most common cause of acute liver failure in the United States and is the most frequently cited reason for withdrawal of an approved drug from the market.1 It occurs at rates of 1 in 1000 to 1 in 100 000 patients, making it difficult to detect in the premarketing randomized controlled trials that are required for drug approval.2 Anticoagulant-induced liver injury has been infrequently reported. Case reports have described the association of anticoagulants with asymptomatic elevation of serum transaminases, clinically significant hepatitis, and fatal liver failure.3–22 As an increasing number of patients receive long-term anticoagulation for prevention of stroke and venous thromboembolism, the rare adverse event of anticoagulant-induced liver injury is gaining attention. Ximelagatran is an oral direct thrombin inhibitor that prevents the conversion of fibrinogen to fibrin by thrombin. This agent is a prodrug and is converted to its active form, melagatran, via hepatic metabolism.23 It has a short half-life, requires twice daily administration, and produces a predictable response after oral administration. It does not require anticoagulant-level or drug-level monitoring, and it has virtually no drug-drug or drug-food …