Marked but Transitory Elevation of Hepatic Transaminases after Subcutaneous Calcium Heparin Administration

Tiziana Tison, Istituto di Semeiotica, IV Cattedra di Medicina Interna, Università di Padova, Via Ospedale, 105, I-35100 Padova (Italy) Heparin is a widely used drug in the management of venous thrombosis. Its adverse effects are not only related to its anticoagulant properties: they also include thrombo-cytopenia [1], cutaneous thrombotic complications [2], disorders of electrolytes [3], and mild elevations of hepatic transaminases [4]. Mild increases in transaminase levels are quite frequent [5] and are usually not accompanied by increases in bilirubin or alkaline phosphatase. We describe a patient who showed severe augmentation of hepatic enzymes after the administration of a single dose of calcium heparin. A 70-year-old Caucasian woman was admitted to our department for chest pain lasting for 8 h. The clinical history revealed chronic ischemic cardiomyopathy and a recent (1991) diagnosis of chronic lymphatic leukemia. The features of the pain were consistent with myocardial ischemia although the electrocardiogram, as well as the assay of specific myocardial enzymes did not show any change. Physical examination did not detect any signs of heart failure. The patient was treated with intravenous nitrates and subcutaneous calcium heparin (7,500 IU every 8 h). On the second day, after a total dose of 15,000 IU heparin, we recorded a marked increment of aspartate (962 U/l) and alanine (ALT) transferase (839 U/l, γ-glutamyl transferases (197 U/l), lactate de-hydrogenase (1,339 U/l) and conjugated bilirubin (35 mol/l). No other biochemical parameter was modified, and in particular platelets remained normal. In order to clarify the meaning of these results, liver echography, serology for hepatitis A, B and C viruses, carcinoembryonic antigen and α-fe-toprotein assays were performed without bringing any insight into the cause of the hepatic disorder. Furthermore, we could reasonably exclude a liver infiltration by the lymphoproliferative disorder because the disease was at stage 0 (according to the Rai classification) and because of the rapid normalization of laboratory parameters without any specific therapy. In fact, the laboratory findings returned to normal values within 15 days, and a few hours after the first determinations, the figures were already reduced to half, although anticoagulant therapy was not discontinued. At the time of admission, the patient was taking oral coronary dilators (nitrates). A possible role of these compounds in the increase in the transaminases seems unlikely for two reasons: firstly, nitrates have never been claimed to increase transaminase levels; secondly, the patient had been