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. 2025 Mar 22;15(1):9874.
doi: 10.1038/s41598-025-94754-z.

Nomogram for the prediction of valproic acid induced platelet decline: a nested case-control study

Gang Cheng  1 , Xinfeng Cai  2 , Tianning Zhang  3 , Jinlin Guo  4 , Jiuhong Ma  1 , Xiufeng Zhang  1 , Xingang Li  5
Affiliations

Nomogram for the prediction of valproic acid induced platelet decline: a nested case-control study

Gang Cheng et al. Sci Rep. .

Abstract

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.

Keywords: Neurosurgery; Nomogram; Platelet decline; Predictive model; Thrombocytopenia; Valproic acid.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Study approval was granted by the Ethics Committee of the Shanxi Provincial People’s Hospital (No. 2019–36). Additionally, this study conformed to the moral standards formulated in the 1964 Declaration of Helsinki and its subsequent amendments or similar ethical guidelines. Written informed consent was waived by the Ethics Committee of Shanxi Provincial People’s Hospital due to the retrospective nature of the study.

Figures

Fig. 1
Fig. 1
Study flowchart.
Fig. 2
Fig. 2
Nomogram for the prediction of valproic acid induced platelet decline.
Fig. 3
Fig. 3
(A) ROC curve for valproic acid induced platelet decline prediction in the training cohort; (B) validation Cohort ROC Curve for valproic acid induced platelet decline prediction.
Fig. 4
Fig. 4
(A) Calibration curves for predicting valproic acid induced platelet decline in the training cohorts. (B) Calibration curve for valproic acid induced platelet decline prediction in the validation cohorts.
See this image and copyright information in PMC

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