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.


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.
Song
X
X
First Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
Huhle
G
G
Wang
L
L
Hoffmann
U
U
Harenberg
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D000925:Anticoagulants / Q000009:adverse effects*; D000991:Antithrombins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
D000906:Antibodies; D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins; D006493:Heparin