Treatment of patients with a history of heparin-induced thrombocytopenia and anti-lepirudin antibodies with argatroban.
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 (gas-chromatography with mass spectrometry), and the generation of lepirudin antibodies (ELISA) were measured. APTT-adjusted dosages for argatroban was 2.0-2.6 microg/kg.min and for lepirudin 48-149 microg/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.
IV. Department of Medicine, University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. j-harenberg@t-online.de
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D000368:Aged; D000906:Antibodies / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects*; D001120:Arginine / Q000031:analogs & derivatives; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D024764:Hirudin Therapy; D006629:Hirudins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000276:immunology; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy / Q000628:therapy*
D000906:Antibodies; D000925:Anticoagulants; D006629:Hirudins; D007074:Immunoglobulin G; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban; C083544:lepirudin