Haematological disturbances during long-term valproate therapy

Abstract

A 14-year-old boy with mental retardation presented with severe thrombocytopenia, macrocytic anaemia and allergic dermatitis. He had been treated with valproate for seizures since the age of 2 years. Clinical examination showed severe purpura, mucous bleeding and extensive dermatitis. Tests to detect serum direct antiplatelet antibodies were positive and bone marrow examination revealed myelodysplastic abnormalities. Valproate was discontinued and both dermatitis and general condition of the child improved with normalization of the full blood count. This report suggests that valproate may produce both peripheral immune thrombocytopenia and severe bone marrow depression several years after the initiation of the therapy.

A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases

“…Myelodysplasia may occur in the BM in a variety of disorders of very different etiologies, eg infection, 27 drug therapy 28 and chronic disease. 29 Non-clonal disorders with dysplastic features, eg mitochondrial disorders like Pearson syndrome, should not be considered as MDS.…”

Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7

“…2 In childhood, MDS with less than 5% blasts in the bone marrow is particularly difficult to diagnose because dysplasia of hematopoietic cells is frequently observed during infection, metabolic disorder, nutritional deficiency, and a variety of other diseases. [3][4][5][6] After treatment of the underlying disorder, these dysplastic changes generally resolve. The presence of a cytogenetic abnormality in hematopoietic cells is helpful in confirming a diagnosis of MDS, but in the absence of such an abnormality the diagnosis is difficult.…”

Valproato de sódio: efeitos colaterais em crianças

“…A sua gênese parece se dever à depressão direta da medula óssea por elevados níveis de valproato de sódio (maiores que 40mg/kg/dia) ou pode ser secundária à destruição imune-mediada, devido à semelhança entre os componentes do valproato de sódio e as membranas celulares. Habitualmente, o quadro é reversível com a redução da dose do medicamento ou sua suspensão (4)(5)(6)(7)(8)(9)(10)(11)(12) . No caso apresentado, o estudo da medula óssea evidenciou a presença de megacariócitos normais e houve resposta satisfatória após o uso de corticoesteróides, confirmando-se o diagnóstico de plaquetopenia de origem imunológica.…”