Argatroban caused severe hypercholesterolaemia in a chronic haemodialysis patient with heparin-induced thrombocytopenia: an unreported adverse effect?

Abstract

Sir, Argatroban is a synthetic direct thrombin inhibitor that is used as an anticoagulant for haemodialysis (HD) in patients with type II heparin-induced thrombocytopenia (HIT) or with antithrombin III deficiency [1,2]. Although there has been no report of hypercholesterolaemia as an adverse effect of argatroban, I recently experienced a case in which severe hypercholesterolaemia was strongly suspected to be induced by argatroban. I took charge of a 67-year-old female chronic-HD patient in September 2007. She received dialysis three times a week for 3.5 h with 40 mg of arogatroban on the basis of the diagnosis of HIT. Because her anti-heparin and platelet factor 4 complex antibody (HIT antibody) was still detected by ELISA [3] then, I continued to use argatroban in her HD. At that time, she was also suffering from severe hypercholesterolaemia. Her serum low-density-lipoprotein cholesterol (LDL-C) was 175 mg/dL in spite of taking simvastatin of 20 mg every day. But she has no familial history of hypercholesterolaemia and she said that she had never been diagnosed as with hypercholesterolaemia until the initiation of HD therapy. I reviewed her hospital record in detail again. She started chronic HD with heparin sodium because her end-stage diabetic nephropathy had deteriorated in January 2007 at another hospital. During the first several HD sessions, her platelet count decreased from 318 000/µL to 82 000/µL and the HIT antibody was detected. She was diagnosed with HIT and the anticoagulant was changed to argatroban. Her platelet count quickly increased and reached to 185 000/µL in only 5 days. Since then, her platelet count has never decreased again. However, according to a series of her laboratory data, her serum total cholesterol, which had been <210 mg/dL until just before initiation of argatroban, began to increase obviously thereafter. She was introduced to our clinic in March 2007. Her total cholesterol had reached 314 mg/dL and her LDL-C was 189 mg/dL at that time. The LDL-C value was extremely higher than 91 mg/dL just before using argatroban at the previous hospital. Soon her LDL-C increased to 210 mg/dL. This value was not reduced until the daily use of simvastatin of 20 mg, as mentioned above, and could not be reduced below 170 mg/dL even after that. (Her LDL-C rather increased a little by the change of the statin to pitavastatin afterwards.) Patients with this LDL-C level are at a high risk of developing coronary artery disease [4]. From