Platelet counts in epileptic children receiving valproic acid

Main Article Content

Lilik Indrayati
Fadhilah Tia Nur
Bambang Soebagyo

Abstract

Background Epileptic seizures are a transient occurrence resulting from abnormal, excessive, or synchronous neural activity in the brain. Epilepsy requires long-term treatment, increasingly larger doses, and combination therapy. Anti-epileptic drugs (AEDs), especially valproic acid (VPA), are the main treatment of choice. Thrombocytopenia is the most common adverse event from AEDs.


Objective To evaluate platelet counts in epileptic children receiving valproic acid monotherapy vs. polytherapy.


Methods This analytic, observational, retrospective cohort study was conducted in children with epilepsy below 18 years of age and treated in Dr. Moewardi Hospital, Surakarta, Central Java. Subjects had received VPA treatment for at least 6 months, either as monotherapy or polytherapy. There were 40 subjects in each group (VPA monotherapy vs. VPA polytherapy). The exclusion criteria were patients who had thrombocytopenia and did not take valproic acid regularly. The data was taken from laboratory and the outcome assessed was decreasing of platelet count.


Results  Administration of VPA as monotherapy vs. polytherapy was not significantly associated with incidence of thrombocytopenia. However, duration of VPA use > 2 years was associated with significantly greater proportion of thrombocytopenia, with OR 33.0 (95%CI 4.157 to 261.962; P=0.001) compared to VPA use < 2 years. Similarly, VPA dose of >30 mg/kg/day was significantly associated with greater proportion of thrombocytopenia, with OR 4.081 (95%CI 1.337 to 12.458; P=0.013) compared to <30 mg/kg/day dosage.


Conclusion Incidence of thrombocytopenia is not significantly different between VPA as a  monotherapy and polytherapy. However, higher VPA dose and longer VPA duration are associated with higher proportion of thrombocytopenia.

Article Details

How to Cite
1.
Indrayati L, Nur F, Soebagyo B. Platelet counts in epileptic children receiving valproic acid. PI [Internet]. 28Jan.2020 [cited 6Apr.2020];60(1). Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2289
Section
Pediatric Neurology
Received 2019-09-03
Accepted 2020-01-28
Published 2020-01-28

References

1. Mikati MA, Hani AJ. Seizure in childhood. In: Kliegman RM, Behrman RE, Jenson RM, editors. Nelson textbook of pediatrics. 20th ed. Philadelphia: Saunders; 2016.
p. 2823. ISBN: 978-0-323-35307-6.
2. Irawan M, Handryastuti S, Risan NA. Epilepsi pada anak. Jakarta: Badan Penerbit IDAI; 2016. p. 6. ISBN: 978-602-0883-19-9.
3. Rosati A, De Masi S, Guerrini R. Antiepileptic drug treatment in children with epilepsy. CNS Drugs. 2015;29:847-63. DOI: 10.1007/s40263-015-0281-8.
4. Kawagoe R, Kawagoe H, Sano K. Valproic acid induces apoptosis in human leukemia cells by stimulating both caspase-dependent and -independent apoptotic signaling pathways. Leuk Res. 2002;26:495–502. DOI: 10.1016/s0145-2126(01)00151-5.
5. Coyle TE, Bair AK, Stein C, Vajpayee N, Mehdi S, Wright J. Acute leukemia associated with valproic acid treatment: a novel mechanism for leukemogenesis? Am J Hematol. 2005;78:256-60. DOI: 10.1002/ajh.20273.
6. Chateauviex S, Eifes S, Morceau F, Grigorakaki C, Schnekenburger M, Henry E, et. Valproic acid pertubs haemotopoietic homeostasis by inhibition of erytoid differentiation and activation of myelomonocytic pathway. Biochem Pharmol. 2011;81:488-509. DOI: 10.1016/j.bcp.2010.11.011.
7. Nasreddine W, Beydoun A. Valproate-induced thrombocytopenia: a prospective monotherapy study. Epilepsia. 2008;49:438-45. DOI: 10.1111/j.1528-1167.2007.01429.x.
8. Elizabeth KE, Gopakumar H, Zachariah P, Jacob RG. Valproate induced thrombocytopenia complicating acute febrile illness. Case report. Ann Indian Acad Neurol. 2006;9:230-2. DOI: 10.4103/0972-2327.29206.
9. Handin RI, Lux SE, Stossel TP. Blood: principles and practice of hematology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2003. p.354. ISBN: 0-7817-1993-3.
10. Ko CH, Kong CK, Tse PW. Valproic acid and thrombocytopenia: cross-sectional study. Hong Kong Med J. 2001;7:15-21. PMID: 11406671.
11. Allarakhia IN, Garofalo EA, Komarynski MA, Robertson PL. Valproic acid and thrombocytopenia in children: A case controlled retrospective study. Pediatric neurology. 1996;14:303-7. DOI: 10.1016/0887-8994(96)00052-5.
12. Mehmood T, Saleem M, Husain SS. Frequency of valproic induced thrombocytopenia in epileptic children. Original article. JUMDC .2014;5:52-5.
13. Roganovic J. Immune thrombocytopenia in children. Med Sci. 2015;43:59-72.
14. Delgado MR, Riela AR, Mills J, Browne R, Roach S. Thrombocytopenia
secondary to high valproate levels in children with epilepsy. J Child Neurol. 1994;9:311-4. DOI: 10.1177/088307389400900318.