Hematological consequences of antiepileptic drug therapy among children with epilepsy

Abstract :

Epilepsy is a chronic neurologic disease that comes third after cerebrovascular and Alzheimer’s disease. Anti-epileptic drugs may affect certain hematological parameters of epileptic patients. Few researchers investigated the hematological adverse effects of antiepileptic drugs in Libya. Thus, the aim was to evaluate hematological parameters in epileptic children who are on antiepileptic drugs. This retrospective study included 83 pediatric patients with epilepsy recruited from Benghazi Children's Hospital, Department of Neurology, from December 2017 to April 2018. Data collected included demographic characteristics, types of epilepsy, anti-epileptic drugs and serum hematological parameters. Hematological parameters recorded included: hemoglobin, hematocrit, platelet, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration and white blood cell count. In all treated patients, regardless of the number of antiepileptic drugs therapy used, the average levels of hematological parameters were significantly lower in the treated group compared to the control group (11.64 gm per dl, 34.53%, 27.74 pg and 33.13 gm per dl, respectively). A significant increase (12.12109 per l) in white blood cell counts in the treated group was found. Average hemoglobin, hematocrit and mean cell hemoglobin concentration levels were significantly lower in patients on poly-therapy compared to mono-therapy and control groups. Average white blood cell counts were significantly increased in patients on anti-epileptic drugs. In sodium valproate users, levels of hematological parameters were significantly decreased but significantly increased in white blood cell counts. In diazepam users, significant increases in white blood cells and platelets but no difference in other parameters were observed. There were no differences in all hematological parameters among patients using carbamazepine except for platelet counts (significantly decreased). In conclusion, there is the substantial effect of the anti-epileptic drugs, especially sodium valproate, on the hematological parameters of children despite the effects were not critical as the changes were still in the normal range.

References

1. Harvey RA, Clark M, Finkel R, Rey J, Whalen K (2019) Lippincott’s illustrated reviews: Pharmacology (5th ed, pp. 530-541). Philadelphia.‏ ISBN: 978-1496384133.
2. Fisher RS, Boas WVE, Blume W, Elger C, Genton P, Lee P, Engel Jr J (2005) Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 46 (4): 470-472.‏ doi: 10.1111/j.0013-9580.2005.66104.x
3. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, Jetté N (2017) Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 88 (3): 296-303.‏ doi: 10.1212/ WNL.0000000000003509
4. Idris A, Alabdaljabar, MS, Almiro A, Alsuraimi A, Dawalibi A, Abduljawad S, AlKhateeb M (2021) Prevalence, incidence, and risk factors of epilepsy in Arab countries: A systematic review. Seizure.‏ 92: 40-50. doi: 10.1016/ j.seizure.2021.07.031
5. Theodore WH, Spencer SS, Wiebe S, Langfitt JT, Ali A, Shafer PO, Vickrey BG (2006) Epilepsy in North America: a report prepared under the auspices of the global campaign against epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization. Epilepsia. 47 (10): 1700-1722.‏ doi: 10.1111/j.1528-1167.2006.00633.x
6. Sridharan R, Radhakrishnan K, Ashok PP, Mousa ME (1986) Epidemiological and clinical study of epilepsy in Benghazi, Libya. Epilepsia. 27 (1): 60-65.‏ doi: 10.1111/j.15281157.1986.tb03502.x
7. Camfield P, Camfield C (2015) Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disorders. 17 (2): 117-123. doi: 10.1684/epd.2015.0736
8. Beghi E (2020) The epidemiology of epilepsy. Neuroepidemiology. 54 (2): 185-191. doi: 10.1159/000503831
9. Korinthenberg R, Burkart P, Woelfle C, Moenting JS, Ernst JP (2007) Pharmacology, efficacy, and tolerability of potassium bromide in childhood epilepsy. Journal of Child Neurology. 22 (4): 414-418.‏‏ doi: 10.1177/088307 3807302758
10. Yasiry Z, Shorvon SD (2012) How phenobarbital revolutionized epilepsy therapy: The story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia. 53 (S8): 26-39. doi: 10.1111/epi.12026
11. Brodie MJ (2010) Antiepileptic drug therapy the story so far. Seizure. 19 (10): 650-655. doi: 10.1016/j.seizure. 2010.10.027‏
12. Sills GJ, Brodie MJ (2001) Update on the mechanisms of action of antiepileptic drugs. Epileptic Disorders. 3 (4): 165-172.‏ PMID: 11844711.
13. Arroyo S, de la Morena A (2001) Life-threatening adverse events of antiepileptic drugs. Epilepsy Research. 47 (1-2): 155-174.‏ doi: 10.1016/s0920-1211(01)00306-0
14. Son YR, Kim YS, Chu K, Lee SK (2013) Oxcarbazepine induced leukopenia. Journal of Korean Epilepsy Society. 17 (1): 22-23.‏ ID: wpr-764818.
15. Kırar H, Türkkan E, Uzunhan TA, Kaçar A, Sazak S, Dikker, O, Dağ (2020) Evaluation of the effects of antiepileptic drugs on complete blood count parameters. Journal of Surgery and Medicine. 4 (12): 1108-1111.‏ doi: 10.28982/ josam.827657
16. Kaushik S, Chopra D, Sharma S, Aneja S (2019) Adverse drug reactions of anti-epileptic drugs in children with epilepsy: A cross-sectional study. Current Drug Safety. 14 (3): 217-224. doi: 10.2174/15748863146661903 11112710
17. Koliqi R, Polidori C, Islami H (2015) Prevalence of side effects treatment with carbamazepine and other antiepileptics in patients with epilepsy. Materia Socio-Medica. 27 (3): 167. doi: 10.5455/msm.2015.27.167-171
18. Farooq N, Ali N, Ullah S (2019) Evaluation of hematological parameters in the genetic prospective in epileptic patients of Khyber Pakhtunkhwa. Pharmacogenomics and Personalized Medicine. 12: 377.‏ doi: 10.2147/PGPM. S223572
19. KM Al-kazzaz, H, Ahmed A, F, K Alsamman, D (2011) The effect of carbamazepine monotherapy on full blood count in epileptic patients. Iraqi Journal of Pharmacy. 11 (1): 13-17.‏ doi: 10.33899/iphr.2011.49576
20. Pottoo FH, Al-Khalifa F, Al-Hassar F, Al-Muhanna S, Al-Ghamdi M, Aljaafari D, Joseph R (2019) Antiepileptic drugs: prescription pattern, hematobiochemical changes and adverse effects: A retrospective study in eastern province of Saudi-Arabia. International Journal of Pharmaceutical Science and Research. 10 (11): 5146-5153. doi: 10.13040/IJPSR.0975-8232.10(11).5146-53
21. Bachmann T, Bertheussen KH, Svalheim S, Rauchenzauner M, Luef, G, Gjerstad, L, Taubøll, E (2011) Haematological side effects of antiepileptic drug treatment in patients with epilepsy. Acta Neurologica Scandinavica. 124: 23-27.‏ doi: 10.1111/j.1600-0404.2011.01539.x
22. Özkaya H, Aydemir G, Akcan AB, Kul M, Karademir F, Aydınöz S, Süleymanoğlu S (2012) Carbamazepine-induced red blood cell aplasia: a case report. Turkish Journal of Hematology. 29 (2): 195-196.‏ ‏doi: 10.5505/ tjh.2012.52296
23. Jain A, Mathur P, Gupta D, Moolrajani K, Saxena GN, Mishra V (2020) Carbamazepine-induced pancytopenia: A rare entity.‏ Journal of Mahatma Gandhi University of Medical Sciences and Technology. 3 (3): 97-98. doi: 10.5005/ jp-journals-10057-0082
24. Yilmazbas P, Şenbil N (2021) Hematological side effects of valproate used for the treatment of epilepsy. Namık Kemal Medical Journal. 9 (1): 39-42. doi: 10.4274/nkmj.galenos.2020.800497
25. Lu RB, Chang YH, Lee SY, Wang TY, Cheng SL, Chen PS, Chen SL (2020) Dextromethorphan protects the valproic acid-induced down regulation of neutrophils in patients with bipolar disorder. Clinical Psycho-pharmacology and Neuroscience. 18 (1): 145.‏ doi: 10.9758/cpn.2020.18.1.145
26. Maksoud HMA, El-Shazly SM, El Saied MH (2016) Effect of antiepileptic drug (valproic acid) on children growth. Egyptian Pediatric Association Gazette. 64 (2): 69-73.‏ doi. 10.1016/j.epag.2016.04.001
27. Carman KB, Özdemir ZC, Kar YD, Gunduz E, Teke HÜ, Arslantas D, Özcan, BÖR (2018) The effect of valproic acid on fetal hemoglobin synthesis in children with epilepsy. Osmangazi Journal of Medicine. 40 (3): 8-12. doi: 10.20515/otd.411757
28. Kaczorowska-Hac B, Matheisel A, Maciejka-Kapuscinska L, Wisniewski J, Alska A, Adamkiewicz-Drozynska E, Balcerska A, Reszczynska I (2012) Anemia secondary to valproic acid therapy in a 13-year-old boy: a case report. Journal of Medical Case Reports. 6: 239. doi: 10.1186/1752-1947-6-239
29. Choi JW, Oh KS (2000) The effects of antiepileptic drugs on hematologic parameters and liver enzymes according to antiepileptic plasma concentrations in epileptic children. Journal of the Korean Child Neurology Society. 8 (1): 70-79. doi: Nil.
30. Nasreddine W, Beydoun A (2008) Valproate‐induced thrombocytopenia: a prospective monotherapy study. Epilepsia. 49 (3): 438-445.‏ doi: 10.1111/j.1528-1167.2007.01429.x
31. Verrotti A, Greco R, Matera, V, Altobelli, E, Morgese, G, Chiarelli, F (1999) Platelet count and function in children receiving sodium valproate. Pediatric Neurology. 21 (3): 611-614.‏ doi: 10.1016/S0887-8994(99)00060-0
32. Kurahashi H, Takami A, Murotani K, Numoto S, Okumura A (2018) Decreased platelet count in children with epilepsy treated with valproate and its relationship to the immature platelet fraction. International Journal of Hematology. 107 (1): 105-111.‏‏ doi: 10.1007/s12185-017-2323-0
33. Ko CH, Kong CK, Tse PW (2001) Valproic acid and thrombocytopenia: cross-sectional study. Hong Kong Medical Journal. 7 (1): 15-21.‏ PMID: 11406671.
34. Rahman A, Mican LM, Fischer C, Campbell AH (2009) Evaluating the incidence of leukopenia and neutropenia with valproate, quetiapine, or the combination in children and adolescents. Annals of Pharmacotherapy. 43 (5): 822-830.‏ doi: 10.1345/aph.1L617
35. Sarkis RA, Jehi L, Silveira D, Janigro D, Najm I (2012) Patients with generalized epilepsy have a higher white blood cell count than patients with focal epilepsy. Epileptic Disorders. 14 (1): 57-63.‏ doi: 1684/epd.2012.0493
36. Bhosale UA, Loharkar NR, Yegnanarayan R, Quraishi N (2014) Study of effects of antiepileptic therapy on various biochemical and hematological parameters patients suffering of epilepsy. International Journal of Basic and Clinical Pharmacology. 3 (1): 79-85. ‏doi: 10.5455/2319-2003.ijbcp20140207
37. Oliva CF, Gangi, G, Marino S, Marino L, Messina, G, Sciuto S, Pavone P (2021) Single and in combination antiepileptic drug therapy in children with epilepsy: how to use it. AIMS Medical Science. 8 (2): 138-146.‏ doi: 10.3934/medsci.2021013
38. Dwajani S, Ranjana G, Sarma GRK, Kulkarni C, Ganapathi B (2014) Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy. International Journal of Basic and Clinical Pharmacology. 3 (4): 692. doi: 10.5455/2319-2003.ijbcp20140827

Citation :

Bengleil et al. (2022) Hematological consequences of antiepileptic drug therapy among children with epilepsy. Mediterr J Pharm Pharm Sci. 2 (1): 44-52. [Article number: 52]. https://doi.org/10.5281/zenodo.6399498