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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2054-2059
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Thrombocytopenia after second exposure to abciximab is caused by
antibodies that recognize abciximab-coated platelets
Brian R. Curtis,
Julia Swyers,
Ajit Divgi,
Janice G. McFarland, and
Richard H. Aster
From the Blood Research Institute and Diagnostic
Laboratories, The Blood Center of Southeastern Wisconsin; Departments
of Medicine and Pathology, Medical College of Wisconsin; and Department
of Medicine, St Luke's Medical Center; Milwaukee, WI.
Thrombocytopenia, often severe, occurs in 1% to 2% of patients
given the fibrinogen receptor antagonist abciximab, a chimeric Fab
fragment containing murine specificity-determining and human framework
sequences. The cause of this complication has not yet been defined.
Studies of 9 patients who developed profound thrombocytopenia (platelets <10 × 109/L [10 000/µL]) within
a few hours of being given abciximab a second time showed that each had
a strong immunoglobulin G (IgG) antibody that recognized platelets
sensitized with abciximab. Five patients also had IgM antibodies. IgG
antibodies reactive with abciximab-coated platelets were also found in
77 (74%) of 104 healthy subjects. However, the patient antibodies
could be distinguished from "normal" ones in 2 ways: (1)
only the patient antibodies reacted preferentially with platelets
sensitized with the intact monoclonal antibody 7E3 from which the
murine sequences in abciximab are derived; and (2) the
"normal" antibodies could be inhibited by Fab fragments derived
from normal human IgG, whereas the patient antibodies were relatively
resistant to this treatment. The findings suggest that antibodies from
the patients are specific for murine sequences in abciximab and are
capable of causing life-threatening thrombocytopenia upon injection of
this drug. The antibodies commonly found in healthy subjects are
specific for the papain cleavage site of any Fab fragments and,
although they react with abciximab-coated platelets, appear not to
cause significant thrombocytopenia. It may be possible to identify
patients at risk for developing thrombocytopenia if given abciximab by
screening for antibodies that recognize 7E3-coated platelets.
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