Epilepsi Tedavisinde Kullanılan Valproatın Hematolojik Yan Etkileri

Amaç: Valproat yaygın olarak kullanılan, tedavi dozlarında hematolojik ve hematolojik olmayan yan etkilere sahip antiepileptik bir ilaçtır. Bu çalışmada; tedavi dozunda kullanılan valproatın bilinen hematolojik yan etkilerinin (trombositopeni, lökopeni, anemi, makrositoz) ilaç kullanım süresi, dozu ve serum seviyesi ile ilişkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Çocuk nöroloji polikliniği tarafından epilepsi tanısı ile takip edilen ve en az 3 aydır valproat kullanmakta olan hastalar çalışma evrenini oluşturmuştur. Hastaların tedavi alma süreleri, kullandıkları valproat dozları, tam kan sayımı ve serum valproat düzeyleri dosyalarından kaydedilmiştir. Valproat dışında ilaç kullanan, başka bir sistemik ve/veya hematolojik hastalığı olan hastalar çalışmaya dahil edilmemiştir. Bulgular: Çalışma kriterlerini karşılayan 112 hastadan 80’inin serum valproat düzeyi ve hemogram sonuçlarına ulaşılabildi. Hastaların 30’u (%37,5) kız idi. Yaş ortalamaları 8,2±4,8 yıl (1-16 yıl), tedavi süreleri ortalaması 19,93±16,4 ay (3 ay-10 yıl) idi. Valproat kullanım dozu 20-60 mg/kg/gün arasında değişmekte idi. Hastaların 34’ünde (%42) en az bir hematolojik yan etki geliştiği saptandı. Bu yan etkiler makrositoz (%18,7), trombositopeni (%17,5), lökopeni (%12,5) ve anemi (%7,5) idi. Trombositopeni ile valproat kullanım süresi arasında ilişki yok iken, ilaç kullanım dozu ve serum seviyesi ile anlamlı ilişki saptandı. Makrositoz ile sadece serum valproat seviyesi arasında ilişki saptandı. Lökopeni ve anemi ile valproat kullanım süresi, dozu ve serum seviyesi arasında ilişki saptanmadı. Sonuç: Epilepsi tedavisinde kullanılan valproatın hematolojik yan etkilerinin nadir olmadığı, bu yan etkilerin önceden tahmin edilemeyeceği görülmektedir. Bu nedenle hastaların takibinde tam kan sayımının değerlendirilmesinin yeterli olacağı ve yan etkiler açısından ailelerin bilgilendirilmesi gerektiği sonucuna varılmıştır.

Hematological Side Effects of Valproate Used for the Treatment of Epilepsy

Aim: Valproate is a commonly used antiepileptic drug with hematologic and non-hematologic side effects at therapeutic doses. The aim of this study was to investigate the relationship between the known hematological side effects of valproate and duration, dose and serum levels of this drug. Materials and Methods: The study population consisted of patients with epilepsy followed by pediatric neurology outpatient clinic, who had been using valproate for at least 3 months. Duration of treatment, valproate doses, hemogram and serum valproate levels of patients were recorded from their files. Patients with other systemic and/or hematological diseases and those who were taking drugs other than valproate were not included in the study. Results: Serum valproate levels and complete blood count results were obtained in 80 of 112 patients who met the criteria. Thirty of them (37.5%) were female. The mean age was 8.2±4.8 years (1-16 years) and the mean duration of treatment was 19.93±16.4 months (3 months-10 years). Valproate use dose ranged from 20 to 60 mg/kg day. At least one hematologic side effect was detected in 34 (42%) patients. These side effects were macrocytosis (18.7%), thrombocytopenia (17.5%), leukopenia (12.5%) and anemia (7.5%). There was no correlation between thrombocytopenia and valproate using time, but a significant correlation was found between dose and serum levels. There was a relationship between macrocytosis and serum valproate level only. No correlation was found between leukopenia and anemia and duration of treatment, dose and serum levels. Conclusion: Hematological side effects of valproate used in the treatment of epilepsy are not uncommon, and these side effects are unpredictable. Therefore, it was concluded that complete blood counts should be sufficient in the follow-up of the patients and families should be informed about the side effects.

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