Objective:

To investigate the joint effect of peripheral blood parameters on the 30-day mortality risk in children with hemophagocytic lymphohistiocytosis (HLH) using weighted quantile sum (WQS) regression.

Approach:

• Study Design: A retrospective cohort design was adopted involving 133 pediatric HLH patients diagnosed at a single center.
• Data Collection: Baseline peripheral blood parameters were collected within 24 hours prior to or on the day of diagnosis.
• Statistical Analysis: Univariate logistic regression was used for preliminary screening, followed by WQS regression to evaluate joint effects and extract empirical weights.
• Additional Analysis: Restricted cubic spline (RCS) analysis explored the dose-response relationship between core parameters and mortality risk.

Key Findings:

• Red blood cell distribution width (RDW), mean corpuscular hemoglobin (MCH), hematocrit (HCT), and hemoglobin (Hb) were significantly associated with early mortality risk.
• The WQS regression model indicated a significant joint protective effect against 30-day mortality risk (β = −0.936, P = 0.012).
• MCH (weight 62.6%) and HCT (weight 29.8%) had the highest relative weights in the evaluated mixture.
• The combined predictive model of MCH and HCT improved the area under the curve (AUC) to 0.728.
• Decision curve analysis confirmed that the combined model provided a favorable clinical net benefit across a range of threshold probabilities.

Interpretation:

Abnormalities in peripheral blood parameters, particularly HCT and MCH, serve as composite indicators for predicting early fatal outcomes in pediatric HLH.

Limitations:

• The study is based on a single-center retrospective cohort, which may limit generalizability.
• Potential confounding factors not accounted for in the analysis.

Conclusion:

The WQS regression model effectively mitigates collinearity interference among clinical variables, providing insights into early mortality risk in pediatric HLH.