Valproate treatment and platelet function:: The role of arachidonate metabolites
Valproate treatment and platelet function:: The role of arachidonate metabolites
复制标题
DOI：
10.1111/j.1528-1157.1999.tb00709.x
复制
发表时间：
1999-03-01
期刊：
影响因子：
5.6
通讯作者：
Vécsei, L
中科院分区：
文献类型：
--
作者：
Kis, B;Szupera, Z;Vécsei, L
目的：丙戊酸盐（VPA）是一种广泛应用于癫痫治疗的药物。VPA最常报告的副作用之一是出血素质。一些作者强调血小板计数降低是VPA诱导的出血素质的基础，但一些报告表明，相当一部分血小板计数正常的患者可能仍有血小板功能改变。VPA诱导血小板功能障碍的机制尚未阐明。血小板功能的决定因素是花生四烯酸级联反应。本离体实验旨在确定VPA引起的止血发生率与该药物对血小板花生四烯酸级联反应的影响之间是否存在关系。（血清水平，36.04 +/- 16.12 μ g/ml; n = 10）或卡马西平（CBZ）处理（血清水平，5.24 +/- 2.67 μ g/ml; n = 10）并用[C-14]花生四烯酸标记。（选择CBZ治疗的患者作为对照组，因为CBZ引起的血液恶液质与VPA引起的血液恶液质相似，但没有CBZ诱导血小板功能障碍的报道。C-14-类花生酸通过超压薄层色谱法分离，并通过液体scillination.Results定量测定：即使当药物的平均血浆浓度低，丙戊酸治疗降低了血小板中花生四烯酸级联的活性。VPA能有效抑制环氧合酶途径和血小板聚集剂血栓素A（2）的合成。结论：血小板花生四烯酸级联反应的抑制可能与VPA引起的血小板功能改变有关。
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 mu g/ml; n = 10) or carbamazepine (CBZ) treatment (serum level, 5.24 +/- 2.67 mu g/ml; n = 10) and were labeled with [C-14]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 C-14-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 A(2).Conclusions: Inhibition of the platelet arachidonate cascade may contribute to the platelet-function alterations caused by VPA.