First Author: Sean Curran, PA-C Co-Author: Jacqueline Stark, Pharm D – Pharmacist, Mayo Clinic Health System Co-Author: Greta Zoesch, DNP, APRN – Nurse Practitioner, Mayo Clinic Health System Co-Author: Ibrahim Mir, N/A – Student, University of Minnesota
Introduction: Levetiracetam (LVE) is a second-generation antiepileptic agent frequently used for seizure management and off-label for seizure prophylaxis in neurocritical care. While generally well tolerated, LVE has been associated with mild hematologic abnormalities and, rarely, pancytopenia requiring discontinuation.1
Description: A 74-year-old male with alcoholic cirrhosis, chronic thrombocytopenia, COPD, hypertension, and malnutrition presented following a fall resulting in subarachnoid and subdural hemorrhage and distal forearm fractures. He was started on LVE for seizure prophylaxis and received blood products including prothrombin complex concentrate, plasma, and platelets. Subsequently, marked declines in hemoglobin (to 5.9g/dL), platelets (to 30×10⁹/L), and leukocytes (1.3×10⁹/L) were observed without evidence of bleeding. LVE was discontinued and replaced with lacosamide. Seven additional units of platelets were required for persistent thrombocytopenia. Laboratory tests revealed elevated D-dimer, reticulocytes, urobilinogen, LDH, and indirect bilirubin, with low fibrinogen and haptoglobin, and a negative Coombs test. Within 24 hours of LVE cessation, hemoglobin improved; platelets and leukocytes also improved within 48 hours.
Discussion: The differential included disseminated intravascular coagulation and hemolysis, but the rapid hematologic recovery following LVE discontinuation suggests acute bone marrow suppression secondary to LVE. A few cases in the literature describe similar acute pancytopenia associated with LVE, though no definitive mechanism has been identified.2,3 Clinicians must remain vigilant for this rare complication and consider discontinuation of LVE if unexplained cytopenia's develop.
References 1. UCB, Inc. Keppra (levetiracetam) [package insert]. US Food and Drug Administration; 2017. Accessed July 26, 2025. 2. Alzahrani T, Kay D, Alqahtani SA, Makke Y, Lesky L, Koubeissi MZ. Levetiracetam induced pancytopenia. Epilepsy Behav Case Rep. 2015;4:45–47. doi:10.1016/j.ebcr.2015.06.001 3. Gallerani M, Boari B, Ceci R, Zama G. Pancytopenia associated with levetiracetam treatment. Epileptic Disord. 2009;11(3):235-237. doi:10.1684/epd.2009.0251
