A 16 year old white boy with trisomy 21 and valproic-acid induced erythrocyte aplasia is reported from the Divisions of Hematology and Oncology, University of Alabama, Birmingham, AL. Suppression of hematopoiesis was demonstrated by in vitro studies of colony-forming-unit granulocyte /macrophage (CTU-GM) assays using bone marrow from healthy adult volunteers cultured in the presence of increasing doses of valproic acid (60, 120, and 240 mcg/ml). At a VPA concentration of 120 mcg/ml, similar to that observed in the patient with erythrocyte aplasia, macrocytosis and neutropenia, there was a 67% CFU-CM growth inhibition, and at VPA levels of 240 mcg/ml, 84% of the colony growth was inhibited. The inhibition was specific to VPA and was not related to a change in pH. The addition of the patient's serum to the assays had no significant effect. The results suggested a direct dose dependent suppression of bone marrow neutrophilic progenitors by valproic acid. [1]
COMMENT. This patient had no family history or medical history of anemia, congenital or acquired bone marrow failure, or malignancies. The only recent drug exposure was valproic acid. The authors recommend close hematologic monitoring of patients receiving valproic acid therapy and especially when larger doses are employed.
Of practical importance in the management of a severe overdose of valproic acid, studies of the elimination half life and clearance of valproic acid in a patient with dialysis-induced encephalopathy who was taking divalproic sodiun for a seizure disorder showed that hemodialysis and heme-perfusion had little effect on the removal of valproic acid from the body. The equilibrium shifted so that valproic acid redistributed back into the blood from the tissues [2]. Hemodialysis is unlikely to benefit patients with toxic overdose of valproic acid.