Drug-induced thrombocytopenia

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2015. | This topic last updated: Sep 03,
2015.
INTRODUCTION The clinician is frequently faced with the problem of a patient presenting with a
low
platelet count (thrombocytopenia) of uncertain cause. One important and reversible cause of
thrombocytopenia is drugs. Drug-induced thrombocytopenia is frequently associated with druginduced
antibodies that cause platelet destruction or clearance by the reticuloendothelial system. This form of
drug-induced thrombocytopenia is also called drug-induced immune thrombocytopenia (DITP).
Immunemediated
thrombocytopenia may also be caused by other substances, such as herbal remedies, foods, and
beverages, in addition to approved drugs. All of these causes are described by the term DITP. Less
common
mechanisms of drug-induced thrombocytopenia include bone marrow suppression by drugs other
than
known cytotoxic (eg, chemotherapy) agents (often dose-dependent), and an immune
thrombocytopenia
(ITP)-like syndrome in which autoimmune platelet destruction continues in the absence of the
implicated
agent. In most cases, thrombocytopenia is the only hematologic manifestation of drug toxicity.
However,
there are exceptions to this general rule:
The pathogenesis, diagnosis, and clinical management of patients with suspected drug-induced
thrombocytopenia will be reviewed here. The general diagnostic approach to the patient with
thrombocytopenia is presented separately. (See "Approach to the adult with unexplained
thrombocytopenia".)
MECHANISMS
Accelerated platelet destruction The usual mechanism of thrombocytopenia caused by
drugs is
accelerated platelet destruction caused by drug-dependent, platelet reactive antibodies. This is
referred to
as drug-induced immune thrombocytopenia (DITP). Following the observation that drug-dependent
antibodies bind to platelets via their Fab regions [1], subsequent studies have documented the various
different mechanisms of drug-dependent antibody formation [2,3].

Heparin-induced thrombocytopenia (HIT) is associated with a hypercoagulable state and thrombosis

rather than bleeding. HIT is discussed separately. (See "Clinical presentation and diagnosis of
heparininduced
thrombocytopenia".)

Some drug-induced disorders, such as aplastic anemia and thrombotic microangiopathy (DITMA),
result in thrombocytopenia along with other cytopenias and organ involvement. (See "Aplastic
anemia:
Pathogenesis; clinical manifestations; and diagnosis", section on 'Drugs' and "Drug-induced
thrombotic
microangiopathy".)

Reversible drug binding to one of the major platelet surface glycoproteins (GP), most commonly GP
Ib/V/IX or GP IIb/IIIa, can cause a protein conformational change [4]. This structural change results in
the exposure of a neoepitope, expressed by a sequence normally concealed within the hydrophobic
domains of the membrane protein.

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