Use of recombinant hirudin as antithrombotic treatment in patients with heparin‐induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia is a rare but severe complication of heparin therapy that can result in severe venous or arterial thromboembolic events and whose treatment remains partially unanswered. Recombinant hirudin is potentially effective as an antithrombotic treatment in the management of heparin-induced thrombocytopenia, given its potent antithrombin effects without known interaction with platelets. We report the results obtained with intravenous recombinant hirudin (HBW 023) administered on a compassionate basis to patients suffering from heparin-induced thrombocytopenia. Six patients suffering from heparin-induced thrombocytopenia were submitted to intravenous recombinant hirudin (HBW 023) administered at a dose of 0.05 mg/kg/hr after an initial bolus injection of 0.07 mg/kg in the case of a venous thromboembolic event, and at a dose of 0.15 mg/kg/hr with the same initial bolus injection in the case of an arterial thromboembolic event. Whenever possible, oral anticoagulation with acenocoumarol was introduced at the same time as recombinant hirudin, which was interrupted as soon as the international normalized ratio reached 3. Clinical events, particularly thromboembolism and bleeding, were noted; activated partial thromboplastin time (aPTT), and platelet count were assessed throughout the administration of recombinant hirudin. Heparins responsible for heparin-induced thrombocytopenia were porcine sodium or calcium heparinate in four cases, nadroparin in one case, and enoxaparin in one case. Thrombocytopenia was discovered on routine systematic platelet count in two patients and after the occurrence of arterial and venous thromboembolism in two patients, respectively. After discontinuation of heparin and the onset of recombinant hirudin, clinical evolution was uneventful in all patients, with no recurrence of thromboembolism, limb amputation, or hemorrhagic complication. The aPTT ratio varied from 1.8 to 3.5 (median 2.4) throughout administration of recombinant hirudin. Platelet count rose from nadir (median value 60 x 10(9), 15 to 90) to above 100 x 10(9)/L in every patient within 3-6 days (median 5), after discontinuation of heparin. Intravenous administration of recombinant hirudin ensured safe anticoagulation in patients with heparin-induced thrombocytopenia and made it possible to wait for oral anticoagulation to become efficient and platelet count to return to normal values without occurrence or recurrence of thromboembolism.

Danaparoid for cardiopulmonary bypass in patients with previous heparin‐induced thrombocytopenia

“…Two new direct antithrombin drugs, Hirudin and Argatroban, may prove to be efficient and safe in patients with HIT undergoing CPB. Both are short acting, and initial experience is encouraging (Matsuo et al, 1992;Schiele et al, 1995). Unfortunately, we were unable to obtain either of these drugs for our patient.…”

A Case Review: Anticoagulation in Hemodialysis Patients with Heparin-Induced Thrombocytopenia

“…Lepirudin is a synthetic recombinant form of hirudin derived from yeast. A prospective trial involving 82 patients with HIT showed it to be a safe and effective alternative anticoagulant [15,16]. Two separate studies involving 6 and 20 patients, respectively, on hemodialysis revealed that lepirudin can be used safely as the sole anticoagulant, though close monitoring was required, as lepirudin is renally cleared [17,18].…”

ACC/AHA/SCAI Practice Guidelines, February 21, 2006

“…Empiric recommendations regarding heparin dosage during coronary angioplasty have been proposed (728,729), but ACT levels after a fixed dose of unfractionated heparin may vary substantially due to differences in body size (730), concomitant use of other medications, including intravenous nitroglycerin (731,732), and in the presence of acute coronary syndromes that increase heparin resistance.…”