Valproik Asitin Epileptik Çocuklarda Fetal Hemoglobin Sentezi Üzerine Etkileri

Öz

Valproik asit çocuklarda epilepsi tedavisinde kullanılmaktadır. En sık görülen yan etkileri hepatotoksisite, anemi ve trombositopenidir. Valproik asit bazı hematolojik hastalıklarda tedavi amacıyla kullanılmaktadır. Epileptik hastalarda fetal hemoglobin üzerine olan etkileri tam olarak araştırılmamıştır. Bu vaka kontrol çalışmasında en az altı aydır valproik asit tedavisi alan epilepsi hastası çocuklar ve sağlıklı gönüllüler dahil edilmiştir. Fetal hemoglobin değerleri, ilaç kan düzeyleri araştırılmıştır. Kırk dört epilepsi hastası çocuk ve 57 sağlıklı çocuk araştırmaya dahil edildi. Ortalama fetal hemoglobin (HbF) yüzdesi epilepsi hastalarında ve kontrol grubunda sırasıyla 0.48 ±0.96 (%) ve 0.25 ±0.61 (%) saptandı. Kan valproik asit düzeyi ile HbF düzeyi arasında anlamlı bir ilişki belirlendi. Çalışmamız valproik asit tedavisinin HbF düzeyini etkilemediğini gösterdi. Epileptik hastalarda HbF yüksekliği belirlenmesi durumunda dikkatli bir araştırma gerekmektedir.

Anahtar Kelimeler

• epilepsi,çocuk,valproik asit,fetal hemoglobin

The Effect of Valproic Acid on Fetal Hemoglobin Synthesis in Children with Epilepsy

Öz

Valproic acid has been used to treat epilepsy in children. The most common side effects are hepatotoxicity, anemia and thrombocytopenia. However the effect of valproic acid on fetal hemoglobin levels has not been revealed adequately. In this study it was aimed to search the effect of valproic acid on hemoglobin levels in children receiving valproic acid. In the present cross sectional study the research group consisted of children with epilepsy who had been receiving valproic acid monotherapy for at least six months. The control group contained children without epilepsy or valproic acid medication. The data from 44 patients and 57 controls were analyzed. The mean percentage of HbF of the study group and control group were 0.48 ±0.96 (%) and 0.25 ±0.61 (%) respectively, and there was no statistical difference between groups. There was a positive relation between blood valproic acid level and HbF levels. The present research showed that valproic acid has no effect on HbF levels. For children on valproic acid therapy, the detection of increased fetal hemoglobin levels must be evaluated carefully.

Anahtar Kelimeler

• epilepsy,valproic acid,children

Kaynakça

1. Olivieri NF. Fetal erythropoiesis and the diagnosis and treatment of hemoglobin disorders in the fetus and child. Semin Perinatol 1997;21:63-692
2. Atweh G, Fathallah H. Pharmacologic induction of fetal hemoglobin production. Hematol Oncol Clin North Am 2010;24:1131-1344.
3. Rönndahl G, Mönkemeyer S, Schulze S, et al. Novel valproic acid derivatives with hemoglobin F inducing activity. Am J Hematol 2006;81:374-376.
4. Conway JM, Leppik IE, Birnbaum AK. Antiepileptic drug therapy in children. In: Swainman’s Pediatric Neurology (5th ed) Philadelphia: Elsevier Saunders, 2011: 811-835.
5. Kieslich M, Schwabe D, Cinatl J Jr, Driever PH. Increase of fetal hemoglobin synthesis indicating differentiation induction in children receiving valproic acid. Pediatr Hematol Oncol 2003;20:15-22.
6. Bachmann T, Bertheussen KH, Svalheim S, et al. Haematological side effects of antiepileptic drug treatment in patients with epilepsy. Acta Neurol Scand Suppl 2011;191:23-27
7. Witt O, Mönkemeyer S, Kanbach K, Pekrun A. Induction of fetal hemoglobin synthesis by valproate. Modulation of MAP kinase pathways. Am J Hematol 2002;71:45-46.
8. Collins AF, Dover GJ. Luban NL. Increased fetal hemoglobin production in patients receiving valproic acid for epilepsy. Blood 1994;84:1690-1691.

9. Selby R, Nisbet-Brown E, Basran RK, Chang L, Olivieri NF. Valproic acid and augmentation of fetal hemoglobin in individuals with and without sickle cell disease. Blood 1997 Jul 15;90:891-893.
10. Fathallah H, Taher A, Bazarbachi A, Atweh GF. Differences in response to fetal hemoglobin induction therapy in -Thalassemia and sickle cell disease. Blood Cells Mol Dis 2009;43:58-62.
11. Vasudev K, Keown P, Gibb I, McAllister-Williams RH. Hematological effects of valproate in psychiatric patients: what are the risk factors? J Clin Psychopharmacol 2010 ;30:282-285