Severe hematologic toxicity of valproic acid. A report of four patients.
Four patients with severe cerebral palsy, mental retardation, and seizures who were treated with valproic acid showed a broad spectrum of hematologic toxicity, which included thrombocytopenia, macrocytic red cells with or without anemia, and the Pelger-Huet anomaly in the segmented neutrophils, along with elevated vitamin B12 levels, normal serum folic acid levels, and elevated fetal hemoglobin values (two cases). Bone marrow findings in all four patients were abnormal, suggestive of a myelodysplastic syndrome. These hematologic findings have not been previously reported and are important for monitoring a patient on valproic acid therapy. The Pelger-Huet anomaly may be mistaken for an elevated band count, the macrocytic anemia appears not to be secondary to a vitamin B12 or folate deficiency, and the thrombocytopenia may be sensitive to drug dosage. The bone marrow changes appear to be a drug-related myelodysplastic phenomenon.
Ganick
D J
DJ
Department of Pediatrics Division of Hematology, East Carolina University School of Medicine, Greenville, North Carolina.
Sunder
T
T
Finley
J L
JL
D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D002675:Child, Preschool; D015672:Erythroid Precursor Cells / Q000473:pathology; D005260:Female; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000473:pathology; D010976:Platelet Count / Q000187:drug effects; D014635:Valproic Acid / Q000009:adverse effects*
D014635:Valproic Acid