Abstracts

Rationale: Valproic acid (VPA) is a widely-used antiepileptic drug for the prevention and treatment of generalized and focal epilepsy. A variety of laboratory hematological abnormalities in the coagulation system that are associated with VPA have been reported.However, no previous study has reported reversible diffuse alveolar hemorrhage (DAH) without thrombocytopenia in a patient receiving VPA monotherapy. Methods: Case : A 15-year-old boy with epilepsy presented with hemoptysis and dyspnea. He had been receiving chronic VPA treatment since age 10 for well-controlled, juvenile myoclonic epilepsy. He had tolerated the VPA well throughout the treatment, without obvious adverse effects and, notably, without any evidence of coagulopathy. He had no past history of bleeding events. And he had not been treated with other medications. Results: On physical examination, we heard crackles over both his lungs. The neurologic examination was normal. Chest radiographs(Figure A, D, E)revealed diffuse lung infiltrations in both lungs, suggestive of DAH, and extensive hemorrhagic aspirations. Laboratory tests showed his hemoglobin was 14.6 mg/dL, and his platelet count was 215,000/mm3. Bleeding time, clotting time, prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen were entirely normal. The patient's plasma VPA level was 69.75 ?g/mL (reference range, 50 to 100 ?g/mL). WBC count was 15100/mL, and CRP was 0.5 mg/dL.To determine the etiology of the pulmonary process, we performed a diagnostic bronchoscopy, with bronchoalveolar lavage (BAL), and a transbronchial biopsy. The bronchoscopy revealed scattered blood aspirates in both bronchial trees, which, upon cytologic examinations of the BAL fluid and transbronchial biopsy specimen, were consistent with alveolar hemorrhage. Cultures for bacteria, fungi, and mycobacteria, as well as viral cultures, from the patient\'s blood, urine, and BAL specimens were negative. Autoimmune antibody tests, including for ANA, ANCA, anti-cardiolipin Ab, and anti-GBM Ab, for Goodpasture's syndrome or vasculitis were also entirely negative. On day 2 after the VPA treatment termination, the patient's chest radiographs showed marked improvement (Figure B). After 1 week, he had recovered completely (Figure C), and with VPA discontinuation, his symptoms did not recur.Conclusions: To our knowledge, this is the first reported case of reversible DAH most likely due to VPA treatment and with no evidence of any other causative disorder or medication. DAH is a progressive condition with high morbidity and mortality. This observation is particularly important, as this patient with apparent VPA-induced DAH made a complete recovery with immediate VPA discontinuation. Fatal complications, without thrombocytopenia, can appear several years after the initiation of VPA therapy. Therefore, neurologists should be aware of VPA-induced pulmonary hemorrhage.