Treatment of Patients with a History of Heparin-Induced Thrombocytopenia and Anti-Lepirudin Antibodies with Argatroban

Author： Job Harenberg Ingrid Jörg Tivadar Fenyvesi Lukas Piazolo

ISSN： 0929-5305

Source： Journal of Thrombosis and Thrombolysis, Vol.19, Iss.1, 2005-02, pp. : 65-69

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Abstract

Patients with heparin-induced thrombocytopenia (HIT) type II require anticoagulation with non-heparin immediate acting anticoagulants. Danaparoid may cross react with HIT-antibodies and lepirudin may generate anti-lepirudin antibodies influencing anticoagulation. We hypothesised, that the synthetic small molecular thrombin inhibitor argatroban does not induce immunoglobulins reacting towards lepirudin in patients with anti-lepirudin antibodies in the history and that titration of the anticoagulation may be easier with argatroban.We report on the treatment of four patients of a study, which was terminated prematurely due to official warnings for a repeated use of lepirudin. Two patients each received argatroban and lepirudin intravenously. A blinded assessor adjusted the doses of the anticoagulants to 1.5–3.0 fold prolongation of the aPTT. Ecarin clotting time (ECT), concentrations of lepirudin (ELISA) and of argatroban (gaschromatoraphy with mass spectrometry,) and the generation of lepirudin antibodies (ELISA) were measured.APTT-adjusted dosages for argatroban was 2.0–2.6 μg/kg⋅ min and for lepirudin 48–149 μ g/kg⋅ h. ECT was prolonged 2.1 to 4.5-fold with lepirudin and 4 to 7-fold with argatroban. The concentration of lepirudin ranged between 750 and 1500 ng/ml and of argatroban between 400 and 1100 ng/ml. Patients on argatroban did not generate immunoglobulin IgG reacting towards lepirudin in contrast to both patients on lepirudin who developed anti-lepirudin antibodies. Both treatments were well tolerated.Despite the low number of patients argatroban seems to lead to a more stable anticoagulant response than lepirudin resulting in a lower variability of the dosage for prophylaxis or treatment of thromboembolism of patients with a history of HIT and lepirudin antibodies.