Severe thrombocytopenia in an acquired immunodeficiency syndrome patient
associated with pentamidine-dependent antibodies specific for glycoprotein
IIb/IIIa
DJ Christie, SC Sauro, AL Cavanaugh and ME Kaplan
University of Minnesota, Department of Laboratory Medicine and Pathology,
Minneapolis 55455.
Severe thrombocytopenia developed in a patient with acquired
immunodeficiency syndrome during treatment with intravenous pentamidine for
Pneumocystis carinii pneumonia. The patient's bone marrow contained
adequate numbers of megakaryocytes, suggesting peripheral platelet
destruction. Platelet counts ranged between less than 3 and 20 x 10(9)/L
for 2 weeks despite cessation of pentamidine, platelet transfusions,
high-dose intravenous IgG, and 2 mg/kg/d prednisone. Thereafter, the
platelet count increased to prepentamidine levels (95 x 10(9)/L0,
permitting rapid withdrawal of steroids. Testing by immunofluorescence
disclosed a high-titer, pentamidine-dependent IgG antibody in the patient's
acute-phase serum that almost entirely disappeared by the time the
patient's platelet count returned to baseline levels. This antibody reacted
only with platelet glycoprotein (GP) IIb/IIIa as shown by antigen-capture
enzyme-linked immunosorbent assay using monoclonal antibodies specific for
various GPs, and was absorbable by normal, but not by GPIIb/IIIa-deficient
platelets (from a patient with Glanzmann's thrombasthenia). The
pentamidine-dependent antibody could not be demonstrated by
immunoprecipitation using the patient's serum and 125I-labeled normal
platelets, although a separate pentamidine-independent antibody was
detected by this method. This latter antibody reacted with two GPs having
molecular weights consistent with GPIIb/IIIa, and was present in
postrecovery as well as acute-phase sera. However, only the
pentamidine-dependent antibody was temporally associated with the severe
thrombocytopenia. Therefore, we believe that these studies demonstrate, for
the first time, that intravenous pentamidine therapy can provoke formation
of drug-dependent antibodies that induce immunologic thrombocytopenia.
Volume 82,
Issue 10,
pp. 3075-3080,
11/15/1993
Copyright © 1993 by The American Society of Hematology