USE OF RECOMBINANT HIRUDIN AS ANTITHROMBOTIC TREATMENT IN PATIENTS WITH HEPARIN-INDUCED THROMBOCYTOPENIA

Heparin-lnduced thrombocytopenia is a rare but severe complication of heparin therapy that can result in severe venous or arterial thromboem bolic events and whose treatment remains partially unanswered. Recombi nant hirudin is potentially effective as an antithrombotic treatment i n the management of heparin-induced thrombocytopenia, given its potent antithrombin effects without known interaction with platelets, We rep ort the results obtained with intravenous recombinant hirudin (HEW 023 ) administered on a compassionate basis to patients suffering from hep arin-induced thrombocytopenia. Six patients suffering from heparin-ind uced thrombocytopenia were submitted to intravenous recombinant hirudi n (HEW 023) administered at a dose of 0.05 mg/kg/hr after an initial b olus injection of 0.07 mg/kg in the case of a venous thromboembolic ev ent, and at a dose of 0.15 mg/kg/hr with the same initial bolus inject ion in the case of an arterial thromboembolic event. Whenever possible , oral anticoagulation with acenocoumarol was introduced at the same t ime as recombinant hirudin, which was interrupted as soon as the inter national normalized ratio reached 3. Clinical events, particularly thr omboembolism and bleeding, were noted; activated partial thromboplasti n time (aPTT), and platelet count were assessed throughout the adminis tration of recombinant hirudin. Heparins responsible for heparin-induc ed thrombocytopenia were porcine sodium or calcium heparinate in four cases, nadroparin in one case, and enoxaparin in one case, Thrombocyto penia was discovered on routine systematic platelet count in two patie nts 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 (media n 2.4) throughout administration of recombinant hirudin. Platelet coun t rose from nadir (median value 60 x 10(9) 15 to 90) to above 100 x 10 (9)/L in every patient within 36 days (median 5), after discontinuatio n of heparin. Intravenous administration of recombinant hirudin ensure d safe anticoagulation in patients with heparin-induced thrombocytopen ia and made it possible to wait for oral anticoagulation to become eff icient and platelet count to return to normal values without occurrenc e or recurrence of thromboembolism. (C) 1995 Wiley-Liss, lnc.