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Predicting the occurrence of thrombocytopenia from free valproate levels: A prospective study

Authors :
Adnan A. Beydoun
Wassim Nasreddine
Omar Nawfal
Ahmad Beydoun
Samir F. Atweh
Maya Dirani
Source :
Seizure. 94:33-38
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Purpose 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. Methods 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. Results 844 trough free VPA levels and concomitant platelet counts obtained from 264 patients were analyzed. In a multivariate analysis, free trough 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. Conclusions 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.

Details

ISSN :
10591311
Volume :
94
Database :
OpenAIRE
Journal :
Seizure
Accession number :
edsair.doi.dedup.....32624bd595ee47528d05e9045c913234