Delayed thrombocytopenia after treatment with abciximab: a distinct clinical entity associated with the immune response to the drug.
BACKGROUND
Acute thrombocytopenia is a recognized side-effect of treatment with the fibrinogen receptor antagonist, abciximab, a chimeric (human/mouse) Fab fragment. The etiology of this complication is not fully understood. Generally, abciximab-induced thrombocytopenia occurs within a few hours of starting treatment with the drug. We have characterized a group of 13 patients who first developed thrombocytopenia 3-6 days after abciximab was discontinued.


OBJECTIVE
To characterize clinical and serological aspects of this newly recognized clinical entity.


METHODS
Clinical information was obtained from attending physicians and review of hospital records. Antibodies reactive with abciximab-coated platelets were characterized by flow cytometry.


RESULTS
In each patient, IgG and/or IgM antibodies reactive with abciximab-coated platelets were identified. These antibodies could be distinguished from similar antibodies present in many normal persons by two criteria-they were relatively resistant to inhibition by normal Fab fragments, and they reacted preferentially with platelets coated with 7E3, the murine monoclonal antibody from which peptide sequences in abciximab are derived. Antibodies with these characteristics were not found in pretreatment serum from three of the thrombocytopenic patients or in patients given abciximab who did not develop thrombocytopenia.


CONCLUSIONS
'Delayed thrombocytopenia' after treatment with abciximab is caused by antibodies produced in response to the drug. These antibodies may be specific for murine peptide sequences in abciximab but could recognize other target epitopes on abciximab-coated platelets. Physicians administering abciximab should be aware of this potential complication of treatment, which usually occurs after discharge from hospital.
Curtis
B R
BR
Blood Research Institute, Blood Center of South-eastern Wisconsin, Milwaukee, WI 53201-2178, USA. brcurtis@bcsew.edu
Divgi
A
A
Garritty
M
M
Aster
R H
RH
D000077284:Abciximab; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000097:blood; D000910:Antibodies, Heterophile / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology* / Q000378:metabolism; D000917:Antibody Formation; D001792:Blood Platelets / Q000378:metabolism; D004342:Drug Hypersensitivity; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology
D000906:Antibodies; D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D000077284:Abciximab