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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2359-2365
An Antibody From a Patient With Ranitidine-Induced Thrombocytopenia
Recognizes a Site on Glycoprotein IX That Is a Favored Target for
Drug-Induced Antibodies
G. Gentilini,
B.R. Curtis, and
R.H. Aster
From the Department of Medicine, Medical College of Wisconsin and the
Blood Research Institute, The Blood Center of Southeastern Wisconsin,
Milwaukee.
Although thrombocytopenia associated with the use of histamine
H2 receptor (H2R) antagonists has been
described, a drug-dependent, platelet-reactive antibody has not
previously been identified in such cases. We studied serum from a
patient who developed acute, severe thrombocytopenia after exposure to
the H2 receptor antagonist, ranitidine, and identified an
antibody that reacted with normal platelets in the presence of this
drug at pharmacologic concentrations. In flow cytometric and
immunoprecipitation studies, the antibody was shown to be specific for
the glycoprotein Ib/IX complex (GPIb/IX). From the pattern of
monoclonal antibody (MoAb) inhibition and the reactions of antibody
with Chinese hamster ovary (CHO) cells transfected with
GPIX and GPIb , we found that the patient's antibody is specific for
an epitope on GPIX close to, or identical with a site recognized by the
MoAb SZ1 that is a common target for antibodies induced by quinine and
quinidine, drugs structurally unrelated to ranitidine. These findings
provide evidence that immune thrombocytopenia can be caused by
sensitivity to an H2 R antagonist and suggest that the SZ1
binding site on GPIX may be a common target for drug-induced
antibodies. Further studies of the epitope for which SZ1 is specific
may provide clues to the mechanism(s) by which drugs promote tight
binding of antibody to a membrane glycoprotein and cause platelet
destruction in patients with drug sensitivity.
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