Eski ve Yeni Kuşak Antiepileptik İlaçların Hemogram Parametrelerine Etkileri Farklı Mı?

Abstract

Amaç: Antinöbet ilaçların (ANİ) neden oldukları hematolojik yan etkilerle ilişkili farklı sonuçlar vardır. Çalışmamızda ANİ’ların hemogram parametrelerine olan etkilerini araştırdık. Gereç ve Yöntemler: En az altı ay AEİ kullanan 156’sı kadın 293 hastanın hemogram değerleri ANİ kullanmayan 36 sağlıklı kontrol grubunun değerleri ile karşılaştırıldı. Ayrıca ANİ olarak eski kuşak antiepileptik ilaçlardan fenitoin (PHT), karbamazepin (KBZ), valproik asit, daha yeni kuşak antiepileptik ilaçlardan levetirasetam, okskarbazepin, pregabalin (PGB), gabapentin ve ikili ANİ kullanan hastaların hemogram değerleri birbirleri ile karşılaştırıldı. Bulgular: ANİ kullanan hastaların kontrol grubu ile karşılaştırmalarında sadece PHT kullananların beyaz kan hücre değerleri kontrol grubuna göre düşük bulundu (p=0.045). Sağlıklı kontrollerde “red cell distribution width” (RDW) değeri ANİ kullananlara göre daha yüksek bulundu (p<0.001). ANİ kullanan gruplar kendi aralarında karşılaştırıldığında eski kuşak ANİ’lardan olan PHT ve KBZ kullananların PGB kullananlara göre beyaz kan hücre değerlerinde anlamlı düşüklük tespit edildi (sırasıyla p=0.006; P=0.005). Sonuç: ANİ’lar hastalarda hematolojik yan etki olarak özellikle beyaz kan hücre düşüklüğüne neden olabilirler. Daha eski kuşak ANİ’lardan olan PHT ve KBZ’in yeni kuşak ANİ’lardan pregabaline göre beyaz kan hücre değerlerinde azalma yapıcı etkileri daha belirgindir. Hastalar için ilaç seçimi yapılırken ve takipleri süresince ANİ’ların hemogram parametreleri üzerine etkileri göz önüne alınmalıdır.

Keywords

• Antinöbet ilaçlar
• hemogram
• beyaz kan hücreleri
• RDW

Are the Effects of Old and New-Generation Antiepileptic Drugs on Hemogram Parameters Different?

Abstract

Aim: There are different comments related to hematological side effects caused by antiseizure drugs (ASDs). In our study, we investigated the effects of ASDs on hemogram parameters. Materials and Methods: Hemogram values of 293 patients including 156 women, who used ASDs for at least six months, were compared with the values of 36 healthy control participants group who did not. In addition, the hemogram values of the patients using old-generation antiepileptic drugs such as phenytoin (PHT), carbamazepine (CBZ), valproic acid were compared with those using new-generation antiepileptic drugs as levetiracetam, oxcarbazepine, pregabalin (PGB), gabapentin and two ASDs in combination. Results: Comparison of the patients using ASDs with the control group revealed that white blood cell (WBC) values of only PHT users were lower than the control group (p=0.045). Red cell distribution width (RDW) values were found to be higher in healthy controls than those using AEDs (p<0.001). When the groups using ASDs were compared among themselves, it was found that the WBC values of the users of old- generation ASDs as PHT and CBZ were significantly lower than those using PGB (p=0.006; P=0.005, respectively). Conclusion: As hematological side effects, ASDs may decrease WBC counts. The WBC decreasing effects of PHT and CBZ, which are older generation antiepileptics, are more pronounced than pregabalin, which is a new- generation antiepileptic drug. The effects of antiepileptic drugs on hemogram parameters of the patients should be taken into consideration while choosing appropriate ASDs and also while following the patient.

Keywords

• Antiseizure drugs
• hemogram
• white blood cells
• RDW

References

1. 1) Bachmann T, Bertheussen KH, Svalheim S et al. Haematological side effects of antiepileptic drug treatment in patients with epilepsy Acta Neurol Scand Suppl 2011;19123-7.
2. 2) O'Connor CR, Schraeder PL, Kurland AH, O'Connor WH. Evaluation of the mechanisms of antiepileptic drug-related chronic leukopenia Epilepsia Jan-Feb 1994;35(1):149-54.
3. 3) Ramsay RE. Use of Phenytoin and Carbamazepine in the Treatment of Epilepsy. Neurologic ClinicsVolume 1986;4(3):585-600.
4. 4) Murphy JE, Stewart RB, Springer PK. Carbamazepine-induced leukocytosis. Am J Hosp Pharm1980;37(4):550-2.
5. 5) Verrotti A , Scaparrotta A, Grosso S, Chiarelli F, Coppola G. Anticonvulsant drugs and hematological disease. Neurol Sci 2014;35(7):983-93.
6. 6) Özkaya H, Aydemir G, Akcan AB et al. Carbamazepine-induced Red Blood Cell Aplasia: A Case Report. Turk J Hematol 2012;29(2):195-196.
7. 7) Hart R G, Easton JD. Carbamazepine and hematological monitoring. Ann Neurol 1982;11(3):309-12.
8. 8) Aliyu H, Ayo JO,Ambali S, et al. Heamatobiochemical Alterations Induced by Carbamazepine and Phenytoin: Mini Review. Biochem Pharmacol (Los Angeles) 2016;5:5.

9. 9) Bhosale UA, Loharkar NR, Yegnanarayan R,Quraishi N. Study of effects of antiepileptic therapy on various biochemical and hematological parameters patients suffering of epilepsy. International Journal of Basic & Clinical Pharmacology. 2014;3(1):79-85.
10. 10) Tutor-Crespo MJ, Hermida J, Tutor JC. Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10, 11-epoxide, and 10-hydroxycarbazepine. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007;151(1):91-4.
11. 11) Handoko KB, Souverein PC, Van Staa TP et al. Risk of Aplastic Anemia in Patients Using Antiepileptic Drugs. Epilepsia 2006;47(7):1232-6.
12. 12) Bartels M, Geest CR, Bierings M, Buitenhuis M, Coffer PJ. Histone deacetylase inhibition modulates cell fate decisions during myeloid differentiation. Haematologica 2010;95(7):1052-60.
13. 13) Davıs RG, Sunder T, Barakat HA, May R. Valproate alters the membrane phospholipids of erythrocytes. Epilepsia 1991;32(suppl 3);11-12.
14. 14) Ozkara C, Dreifuss FE, Apperson Hansen C. Changes in red blood cells with valproate therapy. Acta Neurol Scand 1993;88(3):210-2.
15. 15) Allan RW. Myelodysplastic syndrome associated with chronic valproic acid therapy: a case report and review of the literature. Hematology 2007;12:493–6.
16. 16) Acharya S, Bussel J. Hematologic toxicity of Sodium Valproate. J Pediatr Hematol Oncol 2000;22:62–5.
17. 17) Mori F, Caffarelli C, Caimmi S et al. Drug reaction with eosinophilia and systemic symptoms (DRESS) in children. Acta Biomed 2019;90(Suppl 3):66-79.
18. 18) Weber TH, Knuutila S, Tammisto P, Tontti K. Long-term of phenytoin: Effects on whole blood and red cell folate and haematological parameters. Scand J Haematol 1977;18(2):81-5.
19. 19) Diago MP, Rodríguez MAA, Giner AA, Sirvent MLP. Hematologic alterations and reduction in serum folate in epileptics treated with anticonvulsants. Neurologia1989;4(4):119-23.
20. 20) Sharma TK, Vardey S K, Sitaraman S. Homocysteine Metabolism and Hematological Parameters in Early Stage of Phenytoin Treated Epileptic Children. Clin Lab 2017;63(7):1089-1097.
21. 21) Dinç D, Schulte PFJ. The use of anticonvulsants and the levels of folate, vitamin B12 and homocysteine.Tijdschr Psychiatr 2018;60(1):20-28.
22. 22) Pee DH, Park YK, Eun BL, Park SH, Kim SK. The Hematologic Effect of Antiepileptic Drug. Journal of the Korean Pediatric Society 1997;40(2):217-224.
23. 23) Evans TC, Jehle D. The red blood cell distribution width. J Emerg Med 1991;9(Suppl 1):71-4.
24. 24) Yousefi B, Sanaie S, Ghamari AA, Soleimanpour H, Karimian A, Mahmoodpoor A. Red Cell Distribution Width as a Novel Prognostic Marker in Multiple Clinical Studies. Indian J Crit Care Med 2020;24(1):49-54