Drug-Induced Thrombocytopenia

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Drug-induced thrombocytopenia (DIT) is a relatively common clinical disorder. It is imperative to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis occurs. DIT can be distinguished from idiopathic thrombocytopenic purpura, a bleeding disorder caused by thrombocytopenia not associated with a systemic disease, based on the history of drug ingestion or injection and laboratory findings. DIT disorders can be a consequence of decreased platelet production (bone marrow suppression) or accelerated platelet destruction (especially immune-mediated destruction).

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Clinical Features

Clinically, these patients present with moderate to severe thrombocytopenia (defined as a platelet count of less than 50 × 109/L) and spontaneous bleeding varying from simple ecchymoses, petechiae, and mucosal bleeding to life-threatening spontaneous intracranial hemorrhage. Exclusion of other causes of thrombocytopenia (such as congenital disorders and inflammatory processes), anamnestic analysis (such as a temporal relationship between the administration of the putative drug and the

Etiology

Hundreds of drugs have been implicated in the pathogenesis of DIT. DIT disorders can be a consequence of decreased platelet production or accelerated platelet destruction.

A decrease in platelet production is usually attributable to a generalized myelosuppression, a common and anticipated adverse effect of cytotoxic chemotherapy [12]. In addition, it has been reported that some chemotherapeutic agents can induce thrombocytopenia secondary to an immune-mediated mechanism [13], [14], [15], [16],

Mechanisms of Drug-Induced Immunologic Thrombocytopenia

DITP is a relatively common and sometimes serious clinical disorder characterized by drug-dependent antibodies (DDAbs) that bind to platelets and cause their destruction. Antibodies associated with DITP are unusual in that they typically bind to glycoproteins (GPs) on the cell membrane of the platelets only in the presence of the provocative drug [21], [22]. Hundreds of drugs have been implicated in its pathogenesis; among those, drugs most often associated with DITP are heparin, cinchona

Laboratory Diagnosis

The diagnosis of drug-induced thrombocytopenia is often empiric. In patients exposed only to a single drug, recovery after its discontinuation provides circumstantial evidence that the thrombocytopenia was caused by drug sensitivity [28], [44]. In vitro documentation of platelet-bound immunoglobulins, in the presence of the putative drug, provides direct evidence for the involvement of the tested drug in causing in vivo platelet destruction.

Many different methods have been used to detect the

Summary

DIT disorders can be a consequence of decreased platelet production (bone marrow suppression) or accelerated platelet destruction (especially immune-mediated destruction). Immune-mediated platelet consumption is associated with a large number of drugs leading to DITP in which platelet destruction is caused by immunoglobulins that recognize specific platelet membrane GPs only in the presence of the sensitizing drug noncovalently associated with a specific GP. In some instances, not only the drug

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    This work was supported in part by Grants HL-64704 from the National Heart, Lung, and Blood Institute.

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