Reticulated Platelets and an Optimal Model for Differentiating Thrombocytopenia Etiologies

Objectives This study aimed to investigate the clinical value of reticulated platelets (RtcPLT) percentage derived from an automated hematology analyzer in differentiating thrombocytopenia due to peripheral etiology from decreased bone marrow production (BME). In addition, a secondary objective was to establish specific reference intervals for RtcPLT and to propose an optimal diagnostic model. Methods We conducted a descriptive cross‐sectional study of 375 subjects, including 84 healthy controls and 291 thrombocytopenic patients. The healthy individuals were utilized to establish the RtcPLT reference range. The patient cohort was classified into PE and BME groups based on the results of bone marrow aspiration and biopsy (BMAB). RtcPLT was measured using the optical fluorescence method on the ADVIA 2120i platform. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) analysis and Bayesian model averaging (BMA) to propose the optimal model. Results The median RtcPLT in the BME group (2.28%) was significantly lower than that of the PE group (8.27%, p < 0.001). The single RtcPLT index (cutoff 4.64%) achieved an area under the curve (AUC) of 0.895 (95% confidence interval [95% CI]: 0.858–0.932), showing high sensitivity (90.7%, 95% CI: 81.7%–96.2%), specitificity (82.9%, 95% CI: 77.2%–87.6%) and negative predictive value (NPV) (NPV: 96.2%, 95% CI: 92.4%–98.5%). The optimal model, combining RtcPLT with red blood cells (RBC), neutrophil%, basophil%, retic%, and large unstained cells (LUC%), achieved superior accuracy: AUC value of 0.980 (95% CI: 0.967–0.993), sensitivity of 92.0% (95% CI: 83.4%–97.0%), and specificity of 94.4% (95% CI: 90.5%–97.1%). Conclusion The RtcPLT index measured in this study is a robust, rapid, and automated biomarker for assessing thrombopoietic activity. Furthermore, the optimal model we suggested provides near‐perfect diagnostic accuracy, serving as an expeditious and cost‐effective screening tool to reliably differentiate peripheral and bone marrow etiologies of thrombocytopenia. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission