title: Immunologic response to recombinant hirudin in HIT type II patients during long-term treatment.
abstract: We prospectively investigated 27 patients with heparin-induced thrombocytopenia (HIT) type II who were subsequently treated with r-hirudin. Patients with venous or arterial thromboembolism were treated with activated partial thromboplastin time (aPTT)-controlled intravenous r-hirudin (n = 19; mean 19.3 d) followed by subcutaneous r-hirudin (n = 6; mean 22.5 d) and oral anticoagulation. Patients without thromboembolism were treated with subcutaneous r-hirudin (n = 8; mean 25.9 d). Four patients were readmitted to subcutaneous r-hirudin for a mean duration of 32 d. The incidence of r-hirudin antibodies was 84% for intravenously treated patients and 50% in subcutaneously treated patients. The patients (n = 27) showed a 74% overall incidence of r-hirudin antibodies, mainly of the IgG-subclass, without seroconversion before day 6 and after day 32 of r-hirudin treatment or during r-hirudin treatment. None of the patients showed onset or recurrence of venous or arterial thromboembolism, systemic allergic reactions or IgE-antibody development. During intravenous and subcutaneous administration of r-hirudin the aPTT and the ecarin clotting time was increased in the antibody-positive patients compared to antibody-negative patients. Therefore we assume that r-hirudin antibodies may reduce r-hirudin metabolism.
authors.affiliation: Department of Medicine I, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Huhle
authors.forename: U
authors.initials: U
authors.lastname: Hoffmann
authors.forename: X
authors.initials: X
authors.lastname: Song
authors.forename: L C
authors.initials: LC
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: Heene
authors.forename: J
authors.initials: J
authors.lastname: Harenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation / Q000276:immunology*; D001777:Blood Coagulation / Q000276:immunology; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000276:immunology*; D006801:Humans; D008134:Long-Term Care; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy
chemical_list: D000906:Antibodies; D006629:Hirudins; D006493:Heparin