Hematologic Manifestations of Long‐Term Valproate Therapy

May, Ronald B.; Sunder, Theodore R.

doi:10.1111/j.1528-1157.1993.tb02139.x

Cited by 102 publications

(52 citation statements)

References 17 publications

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“…Many of these toxicities appear to be dose-related [5]. Twenty of 60 patients treated with valproic acid were reported to have significant hematological abnormalities, with thrombocytopenia and macrocytosis being the most common [6]. Serious, but reversible, hematologic toxicity resembling a myelodysplastic syndrome (MDS) has also been reported.…”

Section: Introductionmentioning

confidence: 99%

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

et al. 2005

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Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase. Am.

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Section: Introductionmentioning

confidence: 99%

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

et al. 2005

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“…This problem arises, in part, because therapeutic blood levels are statistical best estimates of the AED levels that produce toxic effects and are often derived from small samples of patients. Even adverse effects that do not seem directly related to the antiepileptic effect of an AED, such as thrombocytopenia with valproate treatment, are dose related (38). Dose-related adverse effects also often increase when multiple AEDs are combined.…”

Section: Rapid Dose Changes High Aed Doses Polypharmacy and Other mentioning

confidence: 99%

Adverse Effects of Antiepileptic Drugs

Greenwood

2000

Epilepsia

107

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Summary:Because the efficacies of antiepileptic drugs (AEDs) are often equivalent, selection of an AED is often determined by adverse effects. Differences in methods for labeling adverse effects and in the adverse effect terms themselves, variations in the populations studied, and inconsistent classifications of adverse effects make it difficult to know how to use information on adverse effects to choose an AED. Effort is underway to develop more extensive and internationally acceptable descriptive terms for adverse effects. Comparison of adverse effects in patients taking AEDs with adverse events in control groups is helpful; however, data from controlled studies are often lacking for most AEDs. Because of these limitations, the clinician must adopt a preventative and early detection approach based on some general principles. This review outlines factors to consider for avoiding and detecting AED adverse effects. The occurrence of weight change with AEDs is reviewed extensively, serving to illustrate how the principle factors can be used to avoid and manage adverse effects and where there is need for better studies of the short-and long-term adverse effects of AEDs.

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“…3 Thrombocytopenia is one of the most common side effects associated with VPA therapy, with incidence ranging from 1% to 30%. 4,5 It is mild to transient in most cases which usually resolves spontaneously on dosage reduction or withdrawal of the drug. 6,7 Available reports showed that thrombocytopenia associated with VPA therapy has been reported to resolve without interruption of VPA treatment 8 and has also been reported to endure over time or to have an erratic course.…”

Section: Introductionmentioning

confidence: 99%