Characteristics of quinine- and quinidine-induced antibodies specific for
platelet glycoproteins IIb and IIIa
GP Visentin, PJ Newman and RH Aster
Blood Center of Southeastern Wisconsin, Milwaukee 53233.
Recent studies have shown that antibodies characteristic of quinine- and
quinidine-induced thrombocytopenia sometimes recognize the platelet
membrane glycoprotein (GP) complex IIb/IIIa in addition to their well known
target, GPIb/IX. We have investigated the frequency with which drug-induced
antibodies bind to GPIIb/IIIa and the nature of their target epitopes. In
studies of sera from 13 patients sensitive to quinidine or quinine, we
found that 10 contained IgG antibodies specific for both GPIb/IX and
GPIIb/IIIa, two reacted with GPIb/IX alone, and one reacted with GPIIb/IIIa
alone. In all cases, the presence of drug was required for binding of IgG
to target GPs. By immunoabsorption, we found that each of five polyspecific
sera contained at least two different antibodies, one reactive with GPb/IX
and the other with GPIIb/IIIa. Further studies with eight drug- dependent
antibodies (DDAb) specific for GPIIb/IIIa showed that three recognized the
GPIIb/IIIa complex only, one recognized GPIIb alone, and three recognized
GPIIIa alone. The eighth serum appeared to bind to both GPIIIa alone and to
an epitope determined by the GPIIb/IIIa complex. The three antibodies
specific for GPIIIa alone also reacted with GPIIIa deglycosylated with
endo-H, and with the major (61 Kd) fragment obtained by chymotryptic
digestion of GPIIIa but failed to react with reduced GPIIIa. These findings
demonstrate that, in drug- induced, immunologic thrombocytopenia, the
anti-platelet immune response is typically directed against epitopes on
both GPIb/IX and GPIIb/IIIa. The three DDAb we studied that were specific
for GPIIIa alone recognize epitopes resistant to chymotrypsin and endo-H
treatment that are dependent on intrachain disulfide bonding.
Volume 77,
Issue 12,
pp. 2668-2676,
06/15/1991
Copyright © 1991 by The American Society of Hematology
