- James N George, MD
James N George, MD
- Professor of Medicine
- University of Oklahoma Health Sciences Center
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 drug-induced 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). Immune-mediated 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:
●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 heparin-induced thrombocytopenia".)
●Some drug-induced disorders, such as aplastic anemia and thrombotic thrombocytopenic purpura, result in thrombocytopenia along with other cytopenias and organ involvement. (See "Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis", section on 'Drugs' and "Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults", section on 'Causes'.)
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".)
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 , subsequent studies have documented the various different mechanisms of drug-dependent antibody formation [2,3].
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- Burgess JK, Lopez JA, Berndt MC, et al. Quinine-dependent antibodies bind a restricted set of epitopes on the glycoprotein Ib-IX complex: characterization of the epitopes. Blood 1998; 92:2366.
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- Aster RH. Drug-induced immune thrombocytopenia: an overview of pathogenesis. Semin Hematol 1999; 36:2.
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- Perdomo J, Yan F, Ahmadi Z, et al. Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro. Blood 2011; 117:5975.
- Gentilini G, Curtis BR, Aster RH. An antibody from a patient with ranitidine-induced thrombocytopenia recognizes a site on glycoprotein IX that is a favored target for drug-induced antibodies. Blood 1998; 92:2359.
- Burgess JK, Lopez JA, Gaudry LE, Chong BH. Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies. Blood 2000; 95:1988.
- Pereira J, Hidalgo P, Ocqueteau M, et al. Glycoprotein Ib/IX complex is the target in rifampicin-induced immune thrombocytopenia. Br J Haematol 2000; 110:907.
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- Curtis BR, McFarland JG, Wu GG, et al. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood 1994; 84:176.
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- Royer DJ, George JN, Terrell DR. Thrombocytopenia as an adverse effect of complementary and alternative medicines, herbal remedies, nutritional supplements, foods, and beverages. Eur J Haematol 2010; 84:421.
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- Patel N, VanDeWall H, Tristani L, et al. A comparative evaluation of adverse platelet outcomes among Veterans' Affairs patients receiving linezolid or vancomycin. J Antimicrob Chemother 2012; 67:727.
- Search on "Drug-induced thrombocytopenia". www.ouhsc.edu/platelets (Accessed on March 14, 2011).
- Nguyen L, Reese JA, George JN. Drug-induced thrombocytopenia. An updated systematic review, 2010. Drug Saf 2011.
- Höchtl T, Pachinger L, Unger G, et al. Antiplatelet drug induced isolated profound thrombocytopenia in interventional cardiology: a review based on individual case reports. J Thromb Thrombolysis 2007; 24:59.
- Bougie D, Aster R. Immune thrombocytopenia resulting from sensitivity to metabolites of naproxen and acetaminophen. Blood 2001; 97:3846.
- Bougie DW, Benito AI, Sanchez-Abarca LI, et al. Acute thrombocytopenia caused by sensitivity to the glucuronide conjugate of acetaminophen. Blood 2007; 109:3608.
- Scognamiglio F, Corso C, Madeo D, et al. Flow cytometry in the diagnosis of drug-induced thrombocytopenia: two illustrative cases. Am J Hematol 2008; 83:326.
- Leach MF, Cooper LK, AuBuchon JP. Detection of drug-dependent, platelet-reactive antibodies by solid-phase red cell adherence assays. Br J Haematol 1997; 97:755.
- Nieminen U, Kekomäki R. Quinidine-induced thrombocytopenic purpura: clinical presentation in relation to drug-dependent and drug-independent platelet antibodies. Br J Haematol 1992; 80:77.
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- Accelerated platelet destruction
- Decreased platelet production
- Antibody specificity
- Reactivity with drug metabolites
- Special mechanisms
- - Heparin
- - Glycoprotein IIb/IIIa inhibitors
- - Prolonged thrombocytopenia
- CLINICAL PRESENTATION
- INITIAL APPROACH
- Confirm thrombocytopenia
- Establish the temporal relationship
- - History of drug ingestion
- - Commonly implicated drugs
- Laboratory testing
- DIFFERENTIAL DIAGNOSIS
- Immune thrombocytopenia (ITP)
- Heparin-induced thrombocytopenia
- Sepsis and DIC
- Other thrombocytopenic disorders
- SUMMARY AND RECOMMENDATIONS