Thrombocytopenia during valproic acid treatment in young patients with new-onset bipolar disorder

Background:. To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function in young patients with new-onset bipolar disorder. Methods: The authors studied 25 new-onset young bipolar patients. Platelet count, platelet aggregation, platelet release, and bleeding time were evaluated before beginning VPA treatment and at least after 10 months of treatment. The control group consisted of 20 sex-matched and age-matched subjects. Patients were started on VPA at a dose of 250 to 750 mg/d, given in divided doses. Mean dosage of VPA was 1137.5 +/- 241.1 mg/d. Mean VPA total plasma concentration was 61.1 +/- 20 g/mL. Results: At baseline, no significant differences were observed for platelet count and function between the bipolar group an the control subjects. After 10 months, at the second evaluation, t e platelet count was significantly lower in the bipolar patients than in the control subjects: 192.7 +/- 21.4mu/L versus 289.8 +/- 23.9mu/L; P < 0.0001. An important observation was that platelet counts were negatively correlated with VPA dose (r = -0.47; P = 0.05) and its plasma concentration (r = -0.50; P = 0.05). In the present study, the authors observed impairment in platelet release of ATP and aggregation that correlated with both VPA dosage and plasma levels. Bleeding times were also significantly longer in patients taking VPA compared with control subjects (P < 0.0001). Conclusion: Thrombocytopenia can appear after a few months of therapy and with plasma VPA levels within the therapeutic range.