The Effect of Long-Term Valproic Acid Monotherapy on Hematological and Biochemical Parameters in Children with Epilepsy

Year 2021, Volume: 9 Issue: 3, 102 - 108, 31.12.2021

Ercan Kayıs Resul Yılmaz , Erhan Karaaslan

https://doi.org/10.21765/pprjournal.871486

Abstract

Objective: The aim of this study is to determine the long-term hematological and biochemical side effects of valproic acid (VPA) in pediatric patients with epilepsy.
Materials and Methods: A retrospective natural study design was used. Participants were pediatric patients with epilepsy who were treated with VPA only as monotherapy. Electronic medical files were reviewed for changes in hematological and biochemical parameters before and after a VPA treatment.
Results: Eighty-five patients aged 3-18 (mean 10.52 ± 3.63) met the study criteria. 50 (58.9%) of the patients were girls. In the second year after starting the treatment, the platelet values of the patients were calculated as 249.32 ± 48.778 in patients using VPA, and this difference over the years is statistically significant. No serious side effects were reported.
Conclusion: Epileptic patients treated with VPA may be at risk of decreased platelet count and elevated liver enzymes. Therefore, baseline measurement of liver function and haematological parameters and monitoring during therapy is recommended.

Keywords

valproic acid, side effects, hematology, thrombocytopenia, liver enzymes

Epilepsi Tanılı Çocuklarda Uzun Süreli Valproik Asit Monoterapisinin Hematolojik Ve Biyokimyasal Parametreler Üzerine Etkisi

Abstract

Amaç: Bu çalışmanın amacı epilepsi tanılı çocuk hastalarda valproik asidin (VPA) uzun süreli hematolojik ve biyokimyasal yan etkilerini belirlemektir.
Gereç ve Yöntem: Geriye dönük bir doğal çalışma tasarımı kullanılmıştır. Katılımcılar, monoteratpi şeklinde yalnızca VPA ile tedavi edilen epilepsi saptanan çocuk hastalardı. Elektronik tıbbi dosyalar, bir VPA tedavisi öncesi ve sonrasında hematolojik ve biyokimyasal parametrelerdeki değişiklikler için gözden geçirildi.
Bulgular: Yaşları 3-18 (ort. 10,52 ± 3,63) olan 85 hasta çalışma kriterlerini karşıladı. Hastaların 50’sini (%58,9) kızlar oluşturmaktaydı. Tedaviye başladıktan sonraki ikinci yılda hastaların Trombosit değerleri VPA kullanan hastalarda ortalama 249,32 ± 48,778 olarak hesaplanmıştır ve yıllar içindeki bu farklılık istatistiksel olarak anlamlıdır. Hiçbir ciddi yan etki bildirilmedi.
Sonuç: VPA ile tedavi edilen epileptik hastalar, trombosit sayısında azalma ve karaciğer enzimlerinde yükselme riski altında olabilir. Bu nedenle, karaciğer fonksiyonlarının ve hematolojik parametrelerin temel ölçümü ve tedavi boyunca izlenmesi önerilir.

Keywords

valproik asit, yan etkiler, hematolojik, trombositopeni, karaciğer enzimleri

References

• 1. Davis R, Peters DH, McTavish D. Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1994;47:332-72.
• 2. Tran AR, Zito JM, Safer DJ, Hundley SD. National trends in pediatric use of anticonvulsants. Psychiatr Serv 2012;63:1095-101.
• 3. Belcastro V, D'Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 2013;107:1-8.
• 4. Kayış E, Yılmaz R, Karaaslan E. Childhood Epilepsy and Valproic Acid and Carbamazepine Treatment: Childhood Epilepsy. Chronicles of Precision Medical Researchers 2020;1:34-44.
• 5. Abaci A, Saygi M, Yis U, Demir K, Dirik E, Bober E. Metabolic alterations during valproic acid treatment: a prospective study. Pediatr Neurol 2009;41:435-9.
• 6. Aggarwal A, Rastogi N, Mittal H, Chillar N, Patil R. Thyroid hormone levels in children receiving carbamazepine or valproate. Pediatr Neurol 2011;45:159-62.
• 7. Aygün F, Ekici B, Aydinli N, Aydin BK, Baş F, Tatli B. Thyroid hormones in children on antiepileptic therapy. Int J Neurosci 2012;122:69-73.
• 8. Voudris K, Attilakos A, Katsarou E, et al. Serum total amylase, pancreatic amylase and lipase activities in epileptic children treated with sodium valproate monotherapy. Brain Dev 2006;28:572-5.
• 9. Gerstner T, Büsing D, Bell N, et al. Valproic acid-induced pancreatitis: 16 new cases and a review of the literature. J Gastroenterol 2007;42:39-48.
• 10. Grauso-Eby NL, Goldfarb O, Feldman-Winter LB, McAbee GN. Acute pancreatitis in children from Valproic acid: case series and review. Pediatr Neurol 2003;28:145-8.
• 11. Schmid MM, Freudenmann RW, Keller F, et al. Non-fatal and fatal liver failure associated with valproic acid. Pharmacopsychiatry 2013;46:63-8.
• 12. Geller B, Luby JL, Joshi P, et al. A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry 2012;69:515-28.
• 13. Pavuluri MN, Henry DB, Carbray JA, Sampson G, Naylor MW, Janicak PG. Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J Affect Disord 2004;82 Suppl 1:S103-11.
• 14. Brigo F, Igwe SC, Lattanzi S. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev 2021;1:Cd003032.
• 15. Tolou-Ghamari Z, Zare M, Habibabadi JM, Najafi M-R. Antiepileptic drugs: a consideration of clinical and biochemical outcome in patients with epilepsy. international journal of preventive medicine 2013;4:330-7.
• 16. Haznedar P, Doğan Ö, Albayrak P, et al. Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies. Epilepsy Res 2019;153:7-13.
• 17. Lo SF. Reference intervals for laboratory tests and procedures. Nelson textbook of pediatrics. 19 ed. Philadelphia: Elsevier; 2011.
• 18. Soyuer F, Erdoğan F. Fiziksel aktivite ve Epilepsi. Sağlık Bilimleri Dergisi (Journal of Health Sciences) 2011;20:77-81.
• 19. Gültekin E, Turanlı G. Epilepsi. In: Yurdakök M, ed. Yurdakök Pediatri. Ankara: Güneş Tıp Kitapevleri; 2017:4385-8.
• 20. Görgülü Ü, Fesci H. Epilepsi ile yaşam: Epilepsinin psikososyal etkileri. Göztepe Tıp Dergisi 2011;26:27-32.
• 21. Toklu Z, Kutlu G, Demirbaş H, Koyuncu G, İnan LE. Ankara Eğitim ve Araştırma Hastanesi Epilepsi Polikliniğine başvuran epilepsi hastalarının demografik ve klinik bulguları. Epilepsi 2012;18:13-8.
• 22. Guerrini R. Epilepsy in children. The Lancet 2006;367:499-524.
• 23. Rosati A, De Masi S, Guerrini R. Antiepileptic Drug Treatment in Children with Epilepsy. CNS Drugs 2015;29:847-63.
• 24. Johannessen CU, Johannessen SI. Valproate: past, present, and future. CNS Drug Rev 2003;9:199-216.
• 25. Cannizzaro E, Albisetti M, Wohlrab G, Schmugge M. Severe bleeding complications during antiepileptic treatment with valproic acid in children. Neuropediatrics 2007;38:42-5.
• 26. May RB, Sunder TR. Hematologic manifestations of long-term valproate therapy. Epilepsia 1993;34:1098-101.
• 27. Cheng R. Thrombocytopenia associated with valproic acid that requires platelet transfusion. Ann Neurol 1989;26:457-8.
• 28. Kishi T, Fujita N, Kawaguchi H, Ishimae M, Watanabe K, Tanaka T. Bone marrow suppression induced by high dose valproic acid. Archives of disease in childhood 1994;71:153-5.
• 29. Acharya S, Bussel JB. Hematologic toxicity of sodium valproate. Journal of pediatric hematology/oncology 2000;22:62-5.
• 30. Sandler R, Emberson C, Roberts G, Voak D, Darnborough J, Heeley A. IgM platelet autoantibody due to sodium valproate. British medical journal 1978;2:1683.
• 31. Tetzlaff JE. Intraoperative defect in haemostasis in a child receiving valproic acid. Canadian journal of anaesthesia 1991;38:222.
• 32. Kis B, Szupera Z, Mezei Z, Gecse Á, Telegdy G, Vécsei L. Valproate treatment and platelet function: the role of arachidonate metabolites. Epilepsia 1999;40:307-10.
• 33. Zeller JA, Schlesinger S, Runge U, Kessler C. Influence of valproate monotherapy on platelet activation and hematologic values. Epilepsia 1999;40:186-9.
• 34. Bedry R, Parrot F. Severe valproate poisoning. Réanimation 2004;13:324-33.
• 35. Zimmerman HJ, Ishak KG. Valproate‐induced hepatic injury: analyses of 23 fatal cases. Hepatology 1982;2:591S-7S.
• 36. Bölükbaşi N, Akar F, Bır S. Antiepileptik İlaçların Lipit Profili ve Karaciğer Enzimleri Üzerine Etkisi. Archives of Neuropsychiatry/Noropsikiatri Arsivi 2011;48.
• 37. Ahmed SN, Siddiqi ZA. Antiepileptic drugs and liver disease. Seizure 2006;15:156-64.
• 38. Voudris KA, Attilakos A, Katsarou E, et al. Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy. Epilepsy research 2006;70:211-7.
• 39. Mujgan Sonmez F, Demir E, Orem A, et al. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes. Journal of child neurology 2006;21:70-4.
• 40. Yamatogi Y. Principles of antiepileptic drug treatment of epilepsy. Psychiatry and clinical neurosciences 2004;58:S3-S6.
• 41. Bjøm K, Gjerstad L, Bentdal Ø, Osnes S, Schrumpf E. Topiramate and fulminant liver failure. The Lancet 1998;352:1119.
• 42. Feldkamp J, Becker A, Witte O, Scharff D, Scherbaum W. Long-term anticonvulsant therapy leads to low bone mineral density—evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Experimental and clinical endocrinology & diabetes 2000;108:37-43.
• 43. Voudris K, Moustaki M, Zeis PM, et al. Alkaline phosphatase and its isoenzyme activity for the evaluation of bone metabolism in children receiving anticonvulsant monotherapy. Seizure 2002;11:377-80.