Influence of valproate monotherapy on platelet activation and hematologic values

Purpose: Valproate (VPA) has been linked to coagulation disturbances, with both impaired and exaggerated clotting, which has been attributed to an eff ect of VPA on platelets or hemostatic proteins. Additional thrombocytic fun ction testing may help to identify patients at risk of increased bleeding c aused by platelet dysfunction. Methods: We evaluated the influence of VPA on hematologic routine values an d platelet activation by using immunostaining and flow cytometry in 30 pati ents receiving long-term VPA therapy and in 30 controls. Results: The fraction of activated platelets was similar in both groups; ho wever, the general extent of platelet activation was significantly lower in the patient group, with considerable interindividual variability. In addit ion, patients had a significantly lower platelet count, prolonged thrombin time, and higher mean corpuscular hemoglobin. Conclusions: Our data confirm the previously reported hematologic changes c aused by VPA and additionally suggest that VPA impairs procoagulatory throm bocytic function, which is reflected by reduced platelet activation and inc reased thrombin time. Possible mechanisms of VPA-platelet interaction are d iscussed.