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Vancomycin-Induced Thrombocytopenia

When an acute decline in platelet count and bleeding occur, vancomycin- or other drug-induced thrombocytopenia should be considered.

Vancomycin is used widely in patients with Staphylococcus aureus infections or with other infections that are unresponsive to other antibiotics. A number of vancomycin-related adverse effects have been reported, including nephrotoxicity, ototoxicity, anaphylactoid reactions ("red-man syndrome"), neutropenia, and, rarely, thrombocytopenia, for which the mechanism has been obscure. However, investigators from Wisconsin and Texas now have acquired data on 34 patients with vancomycin-related thrombocytopenia.

Vancomycin-related thrombocytopenia was associated with platelet counts as low as 13,600 per µL and with severe bleeding. When the drug was withdrawn, platelet counts returned to normal in all patients; however, two patients who received second courses of vancomycin experienced rapid recurrence of thrombocytopenia. Drug-induced platelet-reactive antibodies (IgG, IgM, or both) directed against complexes of vancomycin and platelet glycoprotein (GP) IIb/IIIa or other platelet-membrane glycoproteins were identified in all patients. No antibodies against other drugs to which the patients were exposed were identified; vancomycin-dependent antibodies were not found in patients who received vancomycin but who did not develop thrombocytopenia.

In an accompanying perspective article, the author notes that drug-induced thrombocytopenia can be of three types:

-- Antibody binding to a complex of drug or drug metabolite and platelet glycoprotein (e.g., quinine, vancomycin)

-- Antibody binding to a drug-exposed neoepitope in the GPIIb/IIIa complex (e.g., eptifibatide, tirofiban, abciximab)

-- Antibody recognizing drug-bound platelet factor 4, resulting in platelet activation and thrombosis (e.g., heparin)

Comment: Causes of thrombocytopenia in septic or other acutely ill patients often are multifactorial. Possible origins include suppression of platelet production, platelet consumption due to disseminated intravascular coagulation, dilution accompanying vigorous fluid resuscitation, or heparin-induced coagulation activation. However, in all these situations, thrombocytopenia generally is not very severe, and bleeding is mild. When an acute decline in platelet counts and bleeding occur, vancomycin- or other drug-induced thrombocytopenia should be considered, and the suspected causative agents should be discontinued promptly.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology March 26, 2007

Citation(s):

Von Drygalski A et al. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007 Mar 1; 356:904-10.

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• Medline abstract (Free)

Warkentin TE. Drug-induced immune-mediated thrombocytopenia — From purpura to thrombosis. N Engl J Med 2007 Mar 1; 356:891-3.

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• Medline abstract (Free)