Title:Hematological Consequences of Valproic Acid in Pediatric Patients: A Systematic
Review with a Mechanistic Approach
Volume: 21
Issue: 4
Author(s): Bamdad Riahi-Zanjani, Mohammad Delirrad, Rana Fazeli-Bakhtiyari, Mahood Sadeghi, Hadi Zare-Zardini, Abbas Jafari*Adel Ghorani-Azam*
Affiliation:
- Department of
Forensic Medicine and Toxicology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Cellular and Molecular Research Center, Research Institute on Cellular
and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Department of
Forensic Medicine and Toxicology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
Keywords:
Valproic acid, valproate (VPA), hematological consequences, hematotoxicity, children, pediatric patients.
Abstract: Purpose: Although Valproate (VPA) has several advantages in controlling seizures, it
may cause serious hematological consequences. Hematotoxicity of VPA is particularly important
in pediatrics because patients at this age are at a growing risk of leukemia. For a conclusive agreement
about the toxicity of VPA, in this study, we systematically reviewed the literature in which
the hematological consequences of VPA had been emphasized.
Methods: A systematic literature search was performed in June 2021 on electronic databases to
find original research on the association between VPA therapy and hematotoxicity in pediatric patients.
For this purpose, the following search terms “hematotoxicity”, “valproic acid” and “pediatrics”
with different spellings and similar terms, were searched in the title, keywords, and abstracts
of articles. The data were collected and used for qualitative data description.
Results: A total of 36 relevant articles with an overall 1381 study population were included. The results
showed that VPA could cause severe hematotoxicity in children even at therapeutic doses.
Neutropenia, thrombocytopenia, and bone marrow depression are the most common complications
associated with VPA therapy. Also, findings showed that after discontinuation of VPA and starting
other antiepileptic drugs or reducing the administered VPA dose, hematologic damages were entirely
resolved, and all the hematological parameters improved during two weeks.
Conclusion: This review showed that VPA therapy could cause hematotoxicity in children; hence,
it is recommended to monitor hematological indices during VPA therapy. Also, according to the
suggested mechanistic pathways of VPA side effects, a combination of VPA with antioxidants may
reduce hematological side effects.