De Berardis Domenico, Campanella Daniela, Matera Vincenzo, Gambi Francesco, La Rovere Raffaella, Sepede Gianna, Grimaldi Maria Rosaria, Pacilli Anna Maria, Salerno Rosa Maria, Ferro Filippo Maria
Department of Oncology and Neurosciences, Institute of Psychiatry, University of Chieti, Italy.
J Clin Psychopharmacol. 2003 Oct;23(5):451-8. doi: 10.1097/01.jcp.0000088911.24613.0d.
To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function in young patients with new-onset bipolar disorder.
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.
At baseline, no significant differences were observed for platelet count and function between the bipolar group and the control subjects. After 10 months, at the second evaluation, the platelet count was significantly lower in the bipolar patients than in the control subjects: 192.7 +/- 21.4/microL versus 289.8 +/- 23.9/microL; 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).
Thrombocytopenia can appear after a few months of therapy and with plasma VPA levels within the therapeutic range.
评估丙戊酸（VPA）是否会导致新发性双相情感障碍的年轻患者出现血小板减少及血小板功能受损。
作者研究了25例新发性年轻双相情感障碍患者。在开始VPA治疗前及至少治疗10个月后，评估血小板计数、血小板聚集、血小板释放及出血时间。对照组由20例性别和年龄匹配的受试者组成。患者开始服用VPA，剂量为250至750mg/d，分剂量给药。VPA的平均剂量为1137.5±241.1mg/d。VPA的平均血浆总浓度为61.1±20μg/mL。
基线时，双相情感障碍组与对照组在血小板计数和功能方面未观察到显著差异。10个月后，在第二次评估时，双相情感障碍患者的血小板计数显著低于对照组：192.7±21.4/μL对289.8±23.9/μL；P<0.0001。一个重要的观察结果是，血小板计数与VPA剂量（r=-0.47；P=0.05）及其血浆浓度（r=-0.50；P=0.05）呈负相关。在本研究中，作者观察到ATP的血小板释放和聚集受损，这与VPA剂量和血浆水平均相关。服用VPA的患者出血时间也显著长于对照组（P<0.0001）。
治疗数月后，血浆VPA水平在治疗范围内时可出现血小板减少。
