Generation of Anti-Hirudin Antibodies in Heparin-Induced Thrombocytopenic Patients Treated With R-Hirudin

• DOI: 10.1161/01.cir.100.14.1528
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Xuehong Song; Günter Huhle; Lianchun Wang; Ursula Hoffmann; Job Harenberg
• Keywords: Adult; Aged, 80 and over; Heparin; Anticoagulants; Enzyme-Linked Immunosorbent Assay; Hirudins; Middle Aged; Thrombocytopenia; Antibodies; Antithrombins; Recombinant Proteins; 3. Good health; Immunoglobulin Isotypes; 03 medical and health sciences; 0302 clinical medicine; Immunoglobulin G; Humans; Aged

Background —Hirudin is a small protein with strong thrombin inhibition that may be antigenic. The generation and disappearance of anti-hirudin antibodies were investigated in patients with heparin-induced thrombocytopenia who were treated with recombinant hirudin (r-hirudin) for ≥5 days.

Methods and Results —The IgA, IgE, IgG, and IgM isotypes of anti-hirudin antibodies were determined by ELISA before and after the start of r-hirudin therapy. A total of 56% of patients (13 of 23) developed ≥1 antibody isotype during therapy. No IgE antibodies were generated. IgA, IgG, and IgM antibodies were detected in 30% (7 of 23), 52% (12 of 23), and 17% (4 of 23) of patients, respectively. Four patients generated only IgG, 2 patients developed either IgM or IgG and IgM, 5 patients IgG and IgA, and 2 patients IgG, IgM, and IgA antibodies. IgM antibodies disappeared within 8 days of the cessation of r-hirudin. IgA and IgG antibodies disappeared within 1 year in all but 1 patient. Binding of purified IgG to r-hirudin in IgG antibody–positive patients (n=7) was demonstrated by competitive ELISA for r-hirudin. Of the 7 IgG antibody samples, 1 each neutralized or enhanced the anticoagulant activity of r-hirudin.

Conclusions —R-hirudin may be antigenic in patients with heparin-induced thrombocytopenia. More comprehensive investigations will be required to determine the biological relevance of this and to establish the antibody-generation pattern in other diseases.