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Mechanisms for Linezolid-Induced Anemia and Thrombocytopenia

Principal Scientist, Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD; Associate Professor of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD

Richard F Trotta, MD

at time of writing, Fellow, Division of Infectious Diseases, Walter Reed Army Medical Center, Washington, DC; now, Commander, US Army Health Clinic, Vicenza, Italy

James T Rector, MD

at time of writing, Chief of Hematopathology, Laboratory Service Line, National Naval Medical Center, Bethesda, MD; now, Chief, Naval Ambulatory Care Center, Groton, CT

Jeffery A Tjaden, MD

Fellow, Division of Infectious Diseases, National Naval Medical Center, Bethesda, MD

Anthony J Barile, MD

at time of writing, Staff, Division of Infectious Diseases, National Naval Medical Center; now, Staff, MIMA, Melbourne, FL

Reprints: Wendy B Bernstein MD, Division of Retrovirology, WRAIR, 1600 E. Gude Dr., Rockville, MD 20850-5350, FAX 301/762-7460, E-mail wbernstein{at}hivresearch.org

BACKGROUND: Linezolid has been associated with anemia and thrombocytopenia. Mechanisms for neither have been elucidated.

OBJECTIVE: To propose mechanisms for linezolid-induced anemia and thrombocytopenia.

CASE SUMMARY: A 78-year-old white woman with Staphylococcus epidermidis endocarditis was treated with linezolid after developing resistance to multiple antibiotic regimens. After 7 days of linezolid therapy, she developed thrombocytopenia, while an anemia present since admission remained unchanged. A bone marrow biopsy was performed, primarily looking for a mechanism for the thrombocytopenia. Histopathology revealed adequate megakaryocytes, ringed sideroblasts, and vacuolated pronormoblasts. A course of immune globulin (IVIG) was administered, with slowing in the rate of decline in platelets. She died 24 hours after her last dose of IVIG of congestive heart failure.

DISCUSSION: The presence of ringed sideroblasts and vacuolated pronormoblasts suggests that linezolid-induced anemia is secondary to a chloramphenicol-like suppression of erythropoiesis. The presence of adequate, normal-appearing megakaryocytes suggests immune-mediated thrombocytopenia, not marrow suppression. Although the response to IVIG is difficult to interpret because of the patient's death, there was a slowing in the rate of decline of the platelet count, further supporting immune-mediated thrombocytopenia. An objective causality assessment indicated that the adverse drug event was probably due to linezolid.

CONCLUSIONS: There appear to be 2 distinct mechanisms for linezolid-induced cytopenias. While anemia is reversible and manageable with transfusions, thrombocytopenia can be a treatment-limiting toxicity. The ability to treat through an immune-mediated cytopenia with IVIG may be beneficial for critically ill patients with few therapeutic options.

Key Words: immune thrombocytopenia, intravenous gammaglobulin, linezolid, ringed sideroblasts

Published Online, February 20, 2003. www.theannals.com, DOI 10.1345/aph.1C361

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