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Thrombocytopenia and megakaryocyte dysplasia: an adverse effect of valproic acid treatment.

We describe a 10-year-old girl with thrombocytopenia for 5 months. She has severe cerebral palsy, quadriplegia, developmental delay, and a seizure disorder. She had been treated with valproic acid (Depakene) 53 mg/kg/day t.i.d. for 2 years before presentation. Her platelet count decreased to 28 × 10/L a short time before presentation. Five months ago she was admitted for severe pneumonia; her laboratory values were as follows: platelet count 38 × 10/L, fibrinogen 6.37 (normal 1.60–4.0) g/L, DDI >7,000 (normal 0–449) ng/mL, and International Normalized Ratio 1.6 (normal 0.9–1.1). Other hematologic findings included hemoglobin 66 (normal 120–160) g/L, absolute reticulocyte count 517 (normal 10–100) × 10/L, mean corpuscular volume 98 (normal 80–94) fL, erythrocyte sedimentation rate 130 mm/h, and negative direct antiglobulin test. Vitamin B12 and folate levels were normal. She was successfully treated for pneumonia and did not require platelet transfusions. With the improvement of her clinical condition, her complete blood count and coagulation screen returned to normal except for prolonged thrombocytopenia with limited response to intravenous immunoglobulin. Therefore, a bone marrow aspiration was performed (Fig. 1). This case illustrates one of the hematologic adverse effects of valproic acid, namely thrombocytopenia with megakaryocytic dysplasia. The long-standing thrombocytopenia with valproic acid levels up to 1,115 (normal 350–700) mmol/L before bone marrow aspiration and the improvement after dose reduction of valproic acid, resulting in levels of 517 mmol/l, strongly suggest that they are related to