American University of Beirut Medical Center, PO Box 11-0236, Riad El-Solh 1107 2020 Beirut, Lebanon.
American University of Beirut Medical Center, PO Box 11-0236, Riad El-Solh 1107 2020 Beirut, Lebanon.
Seizure. 2022 Jan;94:33-38. doi: 10.1016/j.seizure.2021.11.018. Epub 2021 Nov 27.
The likelihood of valproate (VPA) induced thrombocytopenia increases with higher VPA levels. In critically ill patients, the biological active free VPA level cannot be predicted from the total serum level. In this study, we evaluated the relationship between trough free VPA serum levels and concomitant platelet counts and assessed risk factors for the development of thrombocytopenia with the aim of generating a formula specifying the probabilities of developing thrombocytopenia based on trough free serum VPA levels.
Trough free VPA levels and concomitant platelet counts were collected from a large cohort of patients who participated in a prospective VPA monotherapy trial. Significant variables associated with thrombocytopenia in a univariate analysis were evaluated in a multivariate model. A receiver operator curve was performed to compute the trough free VPA levels with the greatest discriminating power in predicting thrombocytopenia.
844 trough free VPA levels and concomitant platelet counts obtained from 264 patients were analyzed. In a multivariate analysis, trough free VPA levels, gender, and baseline platelet counts were significantly associated with thrombocytopenia. Using stepwise regression and multivariate logistic regression analyses, we generated gender-specific formulas for predicting platelet counts and probabilities of developing thrombocytopenia. The trough free VPA with the greatest discriminating power to predict platelet values ≤ 100,000/μL was 16.65 µg/mL.
The generated model was based on trough free VPA levels and achieved high sensitivity and specificity. Our results are therefore generalizable and can be applied to estimate the probability of developing thrombocytopenia in critically ill patients.
丙戊酸（VPA）诱导的血小板减少症的可能性随着 VPA 水平的升高而增加。在危重病患者中，无法从总血清水平预测生物活性游离 VPA 水平。在这项研究中，我们评估了谷底游离 VPA 血清水平与同时血小板计数之间的关系，并评估了血小板减少症发展的危险因素，旨在生成一个基于谷底游离血清 VPA 水平指定发生血小板减少症概率的公式。
从参加前瞻性 VPA 单药治疗试验的大量患者中收集谷底游离 VPA 水平和同时的血小板计数。在单变量分析中与血小板减少症相关的显著变量在多变量模型中进行了评估。进行了接收器工作特征曲线以计算预测血小板减少症的谷底游离 VPA 水平具有最大区分能力。
分析了 264 名患者的 844 个谷底游离 VPA 水平和同时的血小板计数。在多变量分析中，谷底游离 VPA 水平、性别和基线血小板计数与血小板减少症显著相关。使用逐步回归和多元逻辑回归分析，我们为预测血小板计数和发生血小板减少症的概率生成了性别特异性公式。预测血小板值≤100,000/μL 的谷底游离 VPA 具有最大区分能力的是 16.65μg/mL。
生成的模型基于谷底游离 VPA 水平，具有较高的灵敏度和特异性。因此，我们的结果是可推广的，可以用于估计危重病患者发生血小板减少症的概率。
