Myelodysplasia From Valproic Acid Resolved by Cessation

Myelodysplastic neoplasms (MDS) are clonal blood disorders that cause ineffective hematopoiesis, low blood counts, and a risk of progression to acute myeloid leukemia. Chemotherapy and radiation usually drive these changes, but a small set of medications, including valproic acid (VPA), can also produce reversible myelodysplastic features. We report a case of VPA-induced myelodysplasia in a middle-aged woman with complex neurologic and psychiatric comorbidities. The patient, with a history of paraplegia secondary to traumatic brain injury and epilepsy, was referred for evaluation of pancytopenia and significant weight loss. She had been treated with VPA for seizure prophylaxis for over a year, with dose escalation to 1000 mg three times daily occurring approximately 3 months prior to presentation. Laboratory evaluation revealed pancytopenia. Peripheral smear showed pseudo-Pelger-Huët cells and thrombocytopenia. Bone marrow biopsy demonstrated mild hypocellularity, erythroid hyperplasia, and dysplasia in the megakaryocytic lineage, but cytogenetic and molecular studies were negative for MDS-associated mutations. We promptly stopped VPA and switched her to lacosamide. Supportive care included a PEG tube for nutrition and one packed red cell transfusion for procedure-related anemia. Her blood counts improved within a week of stopping VPA and normalized completely over the following weeks, with no further cytopenia. This case shows why clinicians should recognize drug-induced myelodysplasia as a reversible mimic of primary MDS. VPA's known hematologic toxicity may stem from its histone deacetylase (HDAC) inhibitor activity, which disrupts normal hematopoiesis. Clinicians should consider VPA-induced myelodysplasia in patients on long-term therapy who present with unexplained cytopenias. Stopping the drug early can produce full hematologic recovery and prevent unnecessary interventions.