AN ANTIBODY FROM A PATIENT WITH RANITIDINE-INDUCED THROMBOCYTOPENIA RECOGNIZES A SITE ON GLYCOPROTEIN-IX THAT IS A FAVORED TARGET FOR DRUG-INDUCED ANTIBODIES

Although thrombocytopenia associated with the use of histamine H-2 rec eptor (H2R) antagonists has been described, a drug-dependent, platelet -reactive antibody has not previously been identified in such cases. W e studied serum from a patient who developed acute, severe thrombocyto penia after exposure to the H-2 receptor antagonist, ranitidine, and i dentified an antibody that reacted with normal platelets in the presen ce of this drug at pharmacologic concentrations. In Row cytometric and immunoprecipitation studies, the antibody was shown to be specific fo r the glycoprotein Ib/IX complex (GPIb/IX), From the pattern of monocl onal antibody (MoAb) inhibition and the reactions of antibody with Chi nese hamster ovary (CHO) cells transfected with GPIX and GPIb beta, 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 H-2 R antagonist and suggest that the SZ1 binding site on GPIX may be a com mon target for drug-induced antibodies. Further studies of the epitope for which SZ1 is specific may provide clues to the mechanism(s) by wh ich drugs promote tight binding of antibody to a membrane glycoprotein and cause platelet destruction in patients with drug sensitivity, (C) 1998 by The American Society of Hematology.