Valproate treatment and platelet function: The role of arachidonate metabolites

Béla Kis, Zoltán Szupera, Zsófia Mezei, Árpád Gecse, Gyula Telegdy, László Vécsei

Research output: Article

32 Citations (Scopus)

Abstract

Purpose: Valproate (VPA) is an extensively used drug in the therapy of epilepsies. One of the most frequently reported side effects of VPA is hemorrhagic diathesis. Some authors emphasized the decreased platelet count as the basis of VPA-induced hemorrhagic diathesis. but some reports suggested that a significant proportion of patients with normal platelet count may still have an altered platelet function. The mechanism of the VPA-induced platelet dysfunction has not yet been elucidated. A determining element of platelet functions is the arachidonate cascade. Present ex vivo experiments were designed to determine whether a relation exists between the incidence of hemostasis caused by VPA and the effect of this drug on the arachidonate cascade of platelets. Methods: Platelets were isolated from patients receiving long-term VPA treatment (serum level, 36.04 ± 16.12 μg/ml; n = 10) or carbamazepine (CBZ) treatment (serum level, 5.24 ± 2.67 μg/ml; n = 10) and were labeled with [14C]arachidonic acid. (CBZ-treated patients were chosen as a control group, because CBZ causes blood dyscrasias similar to those elicited by VPA, but there has been no report that CBZ induces a platelet dysfunction.) The 14C-eicosanoids were separated by means of overpressure thin-layer chromatography and determined quantitatively by liquid scintillation. Results: Even when the mean plasma concentration of the drug was low, VPA treatment reduced the activity of the arachidonate cascade in platelets. VPA effectively inhibited the cyclooxygenase pathway and the synthesis of the strong platelet aggregator thromboxane A2. Conclusions: Inhibition of the platelet arachidonate cascade may contribute to the platelet-function alterations caused by VPA.

Original languageEnglish
Pages (from-to)307-310
Number of pages4
JournalEpilepsia
Volume40
Issue number3
DOIs
Publication statusPublished - jan. 1 1999

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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