International Journal of Hematology

, Volume 107, Issue 1, pp 105–111 | Cite as

Decreased platelet count in children with epilepsy treated with valproate and its relationship to the immature platelet fraction

  • Hirokazu Kurahashi
  • Akiyoshi Takami
  • Kenta Murotani
  • Shingo Numoto
  • Akihisa Okumura
Original Article


This study examined relationships between valproate (VPA) and platelet count and immature platelet fraction (IPF). We compared the platelet count and IPF among three groups of children: those treated with VPA, those treated with other antiepileptic drugs (AEDs), and a reference group. IPF was measured using flow cytometry, and absolute immature platelet count (A-IPC) was calculated. The platelet count was significantly lower in the VPA group than in other AED and reference groups. In all groups, IPF was negatively correlated with platelet count. IPF was significantly higher in the VPA group than in the reference group, whereas A-IPC was similar among all groups. After stratification of the platelet count, IPF and A-IPC of the three groups did not differ significantly in any strata. No relationship was observed between serum VPA level and platelet count, IPF, or A-IPC. Our study suggests that VPA is associated with a decreased platelet count, although thrombocytopoiesis is not affected, even in children with a reduced platelet count. The suppression of platelet production in the bone marrow is unlikely to be the cause of thrombocytopenia in patients treated with VPA.


Immature platelet fraction Valproate Serum level Thrombocytopenia 



This study was partially supported by a grant from the Ministry of Health, Labor, and Welfare.

Compliance wit ethical standards

Conflict of interest

The authors have no conflicts of interest relevant to this article to disclose.


  1. 1.
    Beydoun A, Sackellares JC, Shu V. Safety and efficacy of divalproate sodium monotherapy in partial epilepsy: a double-blind, concentration–response design clinical trial. Neurology. 1997;48:182–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Nasreddine W, Beydoun A. Valproate-induced thrombocytopenia: a prospective monotherapy study. Epilepsia. 2008;49:438–45.CrossRefPubMedGoogle Scholar
  3. 3.
    Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol. 2004;126:93–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Meintker L, Haimerl M, Ringwald J, Krause SW. Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients. Clin Chem Lab Med. 2013;51:2125–32.CrossRefPubMedGoogle Scholar
  5. 5.
    Strauß G, Vollert C, von Stackelberg A, Weimann A, Gaedicke G, Schulze H. Immature platelet count: a simple parameter for distinguishing thrombocytopenia in pediatric acute lymphocytic leukemia from immune thrombocytopenia. Pediatr Blood Cancer. 2011;57:641–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Cremer M, Paetzold J, Schmalisch G, Hammer H, Loui A, Dame C, et al. Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia. Br J Haematol. 2009;144:619–21.CrossRefPubMedGoogle Scholar
  7. 7.
    Have LW, Hasle H, Vestergaard EM, Kjaersgaard M. Absolute immature platelet count may predict imminent platelet recovery in thrombocytopenic children following chemotherapy. Pediatr Blood Cancer. 2013;60:1198–203.CrossRefPubMedGoogle Scholar
  8. 8.
    Adly AA, Ragab IA, Ismail EA, Farahat MM. Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia. Platelets. 2015;26:645–50.CrossRefPubMedGoogle Scholar
  9. 9.
    Yuko S, Takeda T, Hirota A, Hisaeda Y, Amakata S, Nakao A, et al. Examination of the percentage of immature platelet fraction in term and preterm infants at birth. J Clin Neonatol. 2013;2:173–8.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Commission on Classification and Terminology of the International. League against epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389–99.CrossRefGoogle Scholar
  11. 11.
    Briggs C, Longair I, Kumar P, Singh D, Machin SJ. Performance evaluation of the Sysmex haematology XN modular system. J Clin Pathol. 2012;65:1024–30.CrossRefPubMedGoogle Scholar
  12. 12.
    Hong H, Xiao W, Maitta RW. Steady increment of immature platelet fraction is suppressed by irradiation in single-donor platelet components during storage. PLoS One. 2014;9:e85465.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hong H, Xiao W, Stempak LM, Sandhaus LM, Maitta RW. Absolute immature platelet count dynamics in diagnosing and monitoring the clinical course of thrombotic thrombocytopenic purpura. Transfusion. 2015;55:756–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Kanda R. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRefPubMedGoogle Scholar
  15. 15.
    De Berardis D, Campanella D, Matera V, Gambi F, La Rovere R, Sepede G, et al. Thrombocytopenia during valproic acid treatment in young patients with new-onset bipolar disorder. J Clin Psychopharmacol. 2003;23:451–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Allarakhia IN, Garofalo EA, Komarynski MA, Robertson PL. Valproic acid and thrombocytopenia in children: a case-controlled retrospective study. Pediatr Neurol. 1996;14:303–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Zighetti ML, Fontana G, Lussana F, Chiesa V, Vignoli A, Canevini MP, et al. Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis. Epilepsia. 2015;56:e49–52.CrossRefPubMedGoogle Scholar
  18. 18.
    Trannel TJ, Ahmed I, Goebert D. Occurrence of thrombocytopenia in psychiatric patients taking valproate. Am J Psychiatry. 2001;158:128–30.CrossRefPubMedGoogle Scholar
  19. 19.
    Schweinfurth N, Hohmann S, Deuschle M, Lederbogen F, Schloss P. Valproic acid and all trans retinoic acid differentially induce megakaryopoiesis and platelet-like particle formation from the megakaryoblastic cell line MEG-01. Platelets. 2010;21:648–57.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Department of PediatricsAichi Medical UniversityNagakuteJapan
  2. 2.Department of HematologyAichi Medical UniversityNagakuteJapan
  3. 3.Division of Biostatistics, Clinical Research CenterAichi Medical University HospitalNagakuteJapan

Personalised recommendations