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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1409-1414
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a
target glycoprotein in drug-induced thrombocytopenia
Hartmut Kroll,
Qi-Hong Sun, and
Sentot Santoso
From the Institute for Clinical Immunology and
Transfusion Medicine, Justus Liebig University Giessen, Germany; and
The Blood Center of Southeastern Wisconsin, Milwaukee, WI.
Drug-induced immune thrombocytopenia (DITP) is a serious
complication of drug treatment. Previous studies demonstrated that most
drug-dependent antibodies (DDAbs) react with the platelet membrane
glycoprotein (GP) complexes IIb/IIIa and Ib/IX/V. We analyzed the sera
from 5 patients who presented with DITP after intake of carbimazole.
Notably, thrombocytopenia induced by carbimazole was relatively mild in
comparison to patients with DITP induced by quinidine. The sera reacted
with platelets in an immunoassay on addition of the drug. In
immunoprecipitation experiments with biotin-labeled platelets and
endothelial cells, reactivity with the platelet endothelial cell
adhesion molecule-1 (PECAM-1, CD31) could be demonstrated, whereas
neither GPIIb/IIIa nor GPIb/IX was precipitated in the presence of the
drug. These results could be confirmed by GP-specific immunoassay
(MAIPA) using monoclonal antibodies (mabs) against PECAM-1. In
addition, the binding of DDAbs could be abolished by preincubation with
soluble recombinant PECAM-1. Carbimazole-dependent antibodies showed
similar reactivity with platelets carrying the Leu125 and
Val125 PECAM-1 isoforms, indicating that this polymorphic
structure, which is located in the first extracellular domain, is not
responsible for the epitope formation. Binding studies with
biotin-labeled mutants of PECAM-1 and analysis of sera with mabs
against different epitopes on PECAM-1 in MAIPA assay suggested that
carbimazole-dependent antibodies prominently bound to the second
immunoglobulin homology domain of the molecule. Analysis of 20 sera
from patients with quinidine-induced thrombocytopenia by MAIPA assay
revealed evidence that DDAbs against PECAM-1 are involved in addition
to anti-GPIb/IX and anti-GPIIb/IIIa. We conclude that PECAM-1 is an
important target GP in DITP.
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