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The Mechanism for Linezolid (Zyvox) Induced Thrombocytopenia

Summary:

  • Linezolid (Zyvox) is a synthetic oxazolidinone antimicrobial agent that has been known to cause thrombocytopenia.
  • Thrombocytopenia induced by linezolid is thought to occur via a mechanism similar to that of quinine/quinidine-induced immune-mediated platelet destruction.


Editor-in-Chief:
Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed:
November 2015

Explanation

  • Linezolid (Zyvox) is a synthetic oxazolidinone antimicrobial agent that is used in the treatment of infections caused by aerobic Gram-positive bacteria. Linezolid works be inhibiting bacterial protein synthesis by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit. This ultimately prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process during protein synthesis. As it relates to its antimicrobial activity, linezolid has been shown to be both bacteriostatic against enterococcus and staphylococci and bactericidal against streptococci. Unfortunately, one reported complication of linezolid therapy is the potential for myelosuppression.  According to the package insert, Linezolid-associated thrombocytopenia is thought to be dependent on duration of therapy (greater than 2 weeks of treatment).

    Thrombocytopenia induced by linezolid is thought to occur via a mechanism similar to that of quinine/quinidine-induced immune-mediated platelet destruction.  In this scenario, the drug or metabolite binds to platelet membrane glycoprotein IIb/IIIa, which then acts as an antigen to the immune system.  When this occurs, the Fab portion of immunoglobulin G (IgG) antibodies binds to this complex on the platelet surface.  The Fc portion of that IgG antibody bound to the platelet surface then binds to macrophages, when then attack the platelet and clear it from the circulation. This mechanism has been suggested due to the absence of heparin-induced thrombocytopenia (HIT) antibodies or other features of heparin-induced thrombocytopenia/thrombosis (HITT) syndrome, the presence of adequate megakaryocytes in the marrow, and improvement in the rate of decline of platelet count in response to intravenous immune globulin (IVIG) therapy.  Furthermore, if IVIG is given in this situation it can slow platelet destruction through a blocking of the Fc receptors of the antibodies bond to the platelet surface. 

    While the product package insert makes this claim, there is evidence to suggest that this may not linked to the duration of linezolid exposure.

    References:

    1. Bernstein WB, Trotta RF, Rector JT, et al. Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother 2003;37:517-20.
    2. Garazzino S, Guiseppe De Rosa F, Bargiacchi O, et al. Haematological safety of long-term therapy with linezolid. Int J Antimicrob Agents 2007;29:480-3.

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MESH Terms & Keywords

  • Linezolid, Zyvox, Thrombocytopenia, Drug Induced Thrombocytopenia, Linezolid Induced Thrombocytopenia