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Blood, 15 June 2001, Vol. 97, No. 12, pp. 3846-3850
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Immune thrombocytopenia resulting from sensitivity to
metabolites of naproxen and acetaminophen
Daniel Bougie and
Richard Aster
From the Blood Research Institute, The Blood Center of
Southeastern Wisconsin, and the Departments of Medicine and Pathology,
Medical College of Wisconsin, Milwaukee.
In patients suspected of having drug-induced immune
thrombocytopenia, antibodies reactive with normal platelets in the
presence of the suspect drug can sometimes be identified, but negative results are often obtained. One reason for this is that drug
metabolites, formed in vivo, can be the sensitizing agents, but very
little is known about the specific metabolites that can cause this
complication. Five patients were studied who developed thrombocytopenia
after taking the nonsteroidal anti-inflammatory drug naproxen
(3 cases) or acetaminophen (2 cases) but in whom drug-dependent
antibodies could not be detected by means of the unmodified
drugs. In each case, antibodies that reacted with normal target
platelets in the presence of a known drug metabolite (naproxen
glucuronide or acetaminophen sulfate) were identified. Four of the
antibodies were specific for the glycoprotein (GP) IIb/IIIa complex,
but one acetaminophen sulfate-dependent antibody reacted
preferentially with GPIb/IX/V. In patients with a clinical picture
suggestive of drug-induced immune thrombocytopenia, tests for
metabolite-dependent antibodies can be helpful in identifying the
responsible agent.
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