Platelet count and function in children receiving sodium valproate

To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function, the authors prospectively studied 20 children (12 female and eight male; age range 4.9-9.2 years) before and after 6 months of VPA monotherapy. Fifteen healthy sex- and age-matched children served as control subjects. VPA was prescribed at normal dosages (19.7 +/- 9.9 mg/kg), and plasma levels were within the therapeutic range (60.1 +/- 16.5 microg/mL). At the first evaluation, no significant difference between patients and control subjects was observed for platelet count and function. At the second evaluation the platelet counts were significantly lower in the patients (194,200 +/- 37,800/microL; range 157,700-222,400) than in the control subjects (291,100 +/- 41,300/microL; range 261,000-332,500; P < 0.01). Significant differences occurred between patients and control subjects in the release of adenosine triphosphate (ATP) after collagen and adenosine diphosphate (ADP) stimuli and in aggregation after stimulation with collagen, ADP, and arachidonic acid. Significant correlations between platelet count, aggregation, and ATP release and VPA dosage and plasma concentration were also observed. VPA can cause a decreased platelet count and aggregation and ATP release impairment. These side effects can appear after a few months of therapy and with plasma valproate levels within the normal range. They do not seem to be associated with clinical symptoms, and drug discontinuation is not necessary.