Hematologic manifestations of long-term valproate therapy

Sixty patients receiving long-term valproate (VPA) monotherapy were studied for hematologic side effects. All were patients in a long-term care facility and ranged in age from 2 to 29 years (mean 14.6 years). Twenty developed at least one prominent hematologic abnormality. Thrombocytopenia and macrocytosis were the most common findings. In patients with macrocytosis, platelet counts were inversely related to VPA levels. Serum B12 levels were increased in 51 of the patients. In 12 patients with macrocytosis who were extensively studied, no etiology for the increased MCV could be identified. An increased number of Pelger-Huet-like cells was noted in these 12 patients. None of the patients demonstrated hepatic dysfunction. Hematologic toxicity was never severe enough to discontinue therapy and always responded to small decrements in VPA therapy. VPA was discontinued in only 1 patient, owing to poor seizure control.