CASE REPORT The Use of Lepirudin for Anticoagulation in Patients with Heparin-Induced Thrombocytopenia During Major Vascular Surgery Yang Sun, MD, Philip E. Greilich, MD, Steve I. O. Wilson, MD, Mark R. Jackson, MD, and Charles W. Whitten, MD Departments of Anesthesiology & Pain Management and Surgery, University of Texas Southwestern Medical Center, Dallas, Texas H eparin-induced thrombocytopenia (HIT) is one of the most common immune-mediated adverse drug reactions caused by immunoglobulin-G an- tibodies (1). Improved recognition of HIT and increased frequency of repeat heparin exposures in patients with cardiovascular disease has created a clinical dilemma when continued anticoagulation is necessary. Lepirudin (Refludan™ Hoechst Marion Ronssel Inc., Kansas City, MO) is a recombinant hirudin derived from yeast cells and unlike heparin is a direct inhibitor of thrombin that acts independently of antithrombin-III (2). We present two cases in which bolus dosing of lepirudin was used intraoperatively in patients with HIT undergoing major vascular surgery. Case 1 A 71 yr-old male with a history of hypertension, cerebrovas- cular accident, chronic obstructive pulmonary disease, and peripheral vascular disease presented for revision of a fem- oral to posterior tibial artery bypass placed 4 mo previously. The initial procedure was complicated by graft occlusion on postoperative Day 1 requiring emergent thrombectomy and anticoagulation with heparin. On postoperative Day 6, gan- grene of his right first, second, and third toes developed that was also associated with a decrease in platelet count from 208,000 to 103,000/L. A clinical diagnosis of HIT was con- firmed by positive heparin-induced antibodies (heparin/ platelet factor 4 enzyme-linked immunosorbent assay [ELISA]). The patient was treated for acute HIT with lepi- rudin (0.4 mg/kg bolus with continuous infusion at 0.15 mg/kg/hr) for 2 days. Three months later, the patient was readmitted for a sec- ond revision of the bypass graft. All heparin-containing solutions were avoided and the patient received lepirudin 0.4 mg/kg bolus IV before vascular clamping, followed by 0.2 mg/kg every hour. The adequacy of anticoagulation was monitored (every 45 min) by using an activated partial thromboplastin time (aPTT) targeted at 2–2.5 times normal. The operation lasted 6 h and there was no evidence of clinically significant bleeding. At the conclusion of the pro- cedure, lepirudin was not reversed and immediate postop- erative laboratory studies included: prothrombin time 13.9 sec, aPTT 54.2 sec, and platelet count 226,000/L. The pa- tient was transferred to the surgical intensive care unit where lepirudin was infused for 4 days during which time he was transitioned to warfarin. There were no postopera- tive complications and he was discharged home 9 days after surgery. Case 2 A 55 yr-old male with a history of coronary artery disease, diabetes mellitus, and hypertension developed HIT after coronary artery surgery while receiving subcutaneous hep- arin for deep vein thrombosis prophylaxis. His episode of HIT was associated with a decrease in platelet count from 198,000/L to 51,000/L and was complicated by extensive thrombosis resulting in bilateral above-the-knee amputa- tions. The diagnosis of HIT was confirmed by heparin/PF4 ELISA. Because of nonhealing of the amputation wounds, the patient underwent aortoiliac thrombectomy with bal- loon angioplasty and stenting of bilateral iliac artery steno- ses two days after all heparin was stopped. During surgery for thrombectomy and stent placement, he received lepiru- din (0.4 mg/kg initial IV bolus) followed by 0.2 mg/kg boluses of lepirudin every hour for the duration of the procedure. The lepirudin was monitored to maintain aPTT levels of 2–2.5 times normal. There were no intra- or post- operative bleeding complications. Discussion The cases presented in this report demonstrate that bolus only dosing of lepirudin can be used to anticoagulate patients undergoing major vascular surgery with a his- tory of HIT. Our clinical diagnosis was based on the Accepted for publication October 6, 2000. Address correspondence and reprint requests to Philip E. Greilich, MD, Anesthesiology and Pain Management Service (112A), Veterans Affairs North Texas Health Care System, 450. 0 South Lancaster Road, Dallas, TX 75216. Address e-mail to philip. greilich@email.swmed.edu. ©2001 by the International Anesthesia Research Society 344 Anesth Analg 2001;92:344–6 0003-2999/01