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Generation of anti-hirudin antibodies in heparin-induced thrombocytopenic patients treated with r-hirudin

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...

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Hauptverfasser: Song, Xuehong (VerfasserIn) , Huhle, Günter (VerfasserIn) , Wang, Lianchun (VerfasserIn) , Hoffmann, Ursula (VerfasserIn) , Harenberg, Job (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 5 October 1999
In: Circulation
Year: 1999, Jahrgang: 100, Heft: 14, Pages: 1528-1532
ISSN:1524-4539
DOI:10.1161/01.CIR.100.14.1528
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1161/01.CIR.100.14.1528
Verlag, lizenzpflichtig, Volltext: https://www.ahajournals.org/doi/10.1161/01.CIR.100.14.1528
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Verfasserangaben:Xuehong Song, Günter Huhle, Lianchun Wang, Ursula Hoffmann, Job Harenberg

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520 |a 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. 
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