Cheng Gang, Cai Xinfeng, Zhang Tianning, Guo Jinlin, Ma Jiuhong, Zhang Xiufeng, Li Xingang
Department of Neurosurgery, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, People's Republic of China.
Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
Sci Rep. 2025 Mar 22;15(1):9874. doi: 10.1038/s41598-025-94754-z.
Platelet decline is a frequent side effect of valproic acid, a medication commonly prescribed to prevent seizures in neurosurgical patients. However, the risk factors for valproic acid-associated platelet decline remain poorly understood, and it remains unknown whether linezolid or levetiracetam in combination with valproic acid is associated with thrombocytopenia, as both drugs could lead to the decrease in platelet count. This three center, retrospective nested case-control study aimed to develop a predictive model for the prediction of valproic acid-induced platelet decline in a cohort of 356 participants. Multivariate analyses identified advanced age (OR: 1.05; 95% CI 1.03-1.08; P = 0.030) and combination therapy between valproic acid and levetiracetam (OR: 3.03; 95% CI 1.43-6.65; P = 0.005) as independent risk factors, while a trough concentration of valproic acid below 100 μg/mL (OR: 0.41; 95% CI 0.24-0.69; P = 0.010) was an independent protective factor for platelet decline. A nomogram was developed based on these factors, demonstrating robust performance with an area under the curve value of 0.85 in the training cohort and 0.81 in the validation cohort. Calibration plots showed strong agreement between predicted and observed outcomes. This model provides a valuable tool for assessing the risk of platelet decline in valproic acid-treated neurosurgical patients.
血小板减少是丙戊酸常见的副作用,丙戊酸是一种常用于预防神经外科患者癫痫发作的药物。然而,丙戊酸相关血小板减少的危险因素仍知之甚少,同时,由于利奈唑胺和左乙拉西坦都可能导致血小板计数下降,它们与丙戊酸联合使用是否会导致血小板减少也尚不清楚。这项三中心回顾性巢式病例对照研究旨在建立一个预测模型,以预测356名参与者队列中丙戊酸引起的血小板减少情况。多变量分析确定高龄(比值比:1.05;95%置信区间1.03 - 1.08;P = 0.030)以及丙戊酸与左乙拉西坦联合治疗(比值比:3.03;95%置信区间1.43 - 6.65;P = 0.005)为独立危险因素,而丙戊酸谷浓度低于100μg/mL(比值比:0.41;95%置信区间0.24 - 0.69;P = 0.010)是血小板减少的独立保护因素。基于这些因素绘制了列线图,在训练队列中曲线下面积值为0.85,在验证队列中为0.81,显示出强大的性能。校准图显示预测结果与观察结果之间具有高度一致性。该模型为评估接受丙戊酸治疗的神经外科患者血小板减少风险提供了一个有价值的工具。