Predictive Value of Heparin-Binding Protein for Organ Dysfunction and Disease Severity in Pediatric Sepsis: A Retrospective Study

Summary

This article describes a retrospective clinical data analysis workflow for evaluating serial heparin-binding protein measurements and their association with organ dysfunction, disease severity, and short-term outcomes in children with sepsis admitted to a pediatric intensive care unit.

Abstract

Early risk stratification in pediatric sepsis remains difficult because conventional inflammatory markers do not fully reflect endothelial injury or microcirculatory dysfunction. This single-center retrospective observational study evaluated whether heparin-binding protein provides prognostic information for organ dysfunction and disease severity in children with sepsis admitted to the pediatric intensive care unit. A total of 150 children with sepsis admitted to the People’s Hospital of Guangxi Zhuang Autonomous Region, China, were included. Heparin-binding protein and routine inflammatory markers were measured within 24 h of admission and again approximately 48 h later. Absolute and relative short-term changes in the heparin-binding protein were calculated. Outcomes included pediatric Sequential Organ Failure Assessment-defined early organ dysfunction progression, high illness severity, organ support requirements, and 28-day all-cause mortality. Prognostic performance was assessed using receiver operating characteristic analysis, multivariable logistic regression, Cox regression, calibration assessment, and reclassification metrics. Higher baseline heparin-binding protein levels and unfavorable early trajectories were associated with greater organ dysfunction, higher illness severity, and more frequent use of mechanical ventilation, vasoactive therapy, and renal replacement therapy. Heparin-binding protein demonstrated superior discriminative performance compared with conventional inflammatory biomarkers and remained independently associated with adverse outcomes after adjustment for organ dysfunction scores and routine laboratory indices. Adding heparin-binding protein metrics to models containing clinical scores and standard biomarkers improved discrimination and risk reclassification. These findings suggest that early, serial heparin-binding protein assessment may provide useful prognostic information and complement existing risk assessment frameworks for pediatric sepsis in the pediatric intensive care unit.

Introduction

Sepsis is an infection-triggered dysregulated host response that causes life-threatening organ dysfunction and remains a major cause of mortality and disability in pediatric intensive care¹. Recent epidemiological and clinical evidence indicate that pediatric sepsis continues to impose a substantial global burden, with children admitted to the pediatric intensive care unit (PICU) facing high risks of circulatory instability, respiratory failure, and multiple organ dysfunction². Current management emphasizes early recognition and timely intervention, including antimicrobial therapy, fluid resuscitation, vasoactive support....

Protocol

This study was approved by the institutional ethics committee of the People’s Hospital of Guangxi Zhuang Autonomous Region (IRB approval no. KY-ZC-2023-035). The requirement for informed consent was waived because this retrospective analysis used de-identified clinical data collected during routine care.

Study design and setting
This was a single-center retrospective observational cohort study conducted in the Pediatric Intensive Care Unit (PICU) of the People’s Hospital of Guangxi Zhuang Autonomous Region. Consecutive PICU admissions between January 1, 2022, and December 31, 2025, were screened. Clinical ....

Results

Baseline characteristics by HBP strata and early organ dysfunction progression status
A total of 150 children with sepsis were included in the final analysis cohort. When patients were stratified by baseline heparin-binding protein (HBP) quartiles, baseline HBP increased from 21.1 ng/mL (interquartile range [IQR], 15.9–26.2) in Q1 to 262.8 ng/mL (IQR, 201.6–308.7) in Q4 (p < 0.001; Table 1). Age, sex, body weight, and chronic comorbidity were broadly comparable across quartiles. I.......

Discussion

This retrospective pediatric intensive care unit (PICU) cohort found that heparin-binding protein (HBP) was closely associated with organ dysfunction burden and disease severity in pediatric sepsis and provided additional prognostic information beyond conventional inflammatory markers⁹. Higher baseline HBP levels and larger short-term increases were associated with higher pediatric Sequential Organ Failure Assessment (pSOFA) scores, greater need for mechanical ventilation, vasoactive therapy, cont.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Analysis script set	Study investigators	Script package set version 1.0	Version-controlled R script set used for data cleaning, descriptive statistics, ROC analysis, logistic regression, Cox regression, calibration analysis, reclassification analysis, subgroup analysis, and figure/table generation.
Automated clinical chemistry/immunoassay analyzer	Hospital central laboratory platform	Institutional system, not commercially cataloged	Fully automated clinical chemistry/immunoassay platform used in the hospital central laboratory for routine biomarker testing. Exact platform was maintained under the laboratory’s standard operating procedure.
Base R stats package	R Foundation for Statistical Computing	Included in R 4.3.2	Used for standard descriptive statistics, Shapiro-Wilk tests, t-tests, chi-square tests, Fisher’s exact tests, and nonparametric tests where applicable.
Clinical data dictionary	Study investigators	Clinical data dictionary version 1.0	Investigator-developed data dictionary defining demographics, infection source, comorbidities, interventions, organ support variables, pSOFA components, and outcome fields.
cobas e immunoassay analyzer series	Roche Diagnostics	Platform-dependent; no single reagent catalog number	Compatible analyzer family for Roche Elecsys assays, including IL-6. Used where cytokine testing was ordered as part of routine care.
Critical care information system	Pediatric Intensive Care Unit, People’s Hospital of Guangxi Zhuang Autonomous Region	Institutional system, not commercially cataloged	Source system for pediatric intensive care unit admission time, organ support records, mechanical ventilation, vasoactive therapy, fluid bolus volume, continuous renal replacement therapy, and pediatric Sequential Organ Failure Assessment-related variables.
De-identified analysis dataset	Study investigators	Institutional dataset, not commercially cataloged	De-identified retrospective dataset containing eligible pediatric sepsis admissions, biomarker measurements, organ support records, pSOFA variables, and 28-day outcome data. Access is subject to institutional ethics and data-governance approval.
Diluent MultiAssay	Roche Diagnostics	7299010190	Sample diluent listed for Roche Elecsys IL-6 assay workflows.
Electronic medical record system	People’s Hospital of Guangxi Zhuang Autonomous Region	Institutional system, not commercially cataloged	Source system for demographic data, diagnosis records, clinical notes, comorbidities, treatment information, vital signs, organ support events, and outcome follow-up.
Graphing and table-generation scripts	Study investigators	Included in script package set version 1.0	Used to generate publication figures, analytical tables, receiver operating characteristic curves, time-dependent AUC plots, and subgroup displays from the locked analysis dataset.
Human Interleukin-8 ELISA Kit	Thermo Fisher Scientific / Invitrogen	BMS204-3	Enzyme-linked immunosorbent assay kit for quantitative detection of human interleukin-8. Included as the interleukin-8 assay source when interleukin-8 testing was available in the laboratory information system.
Human Interleukin-8 ELISA Kit, ten-plate format	Thermo Fisher Scientific / Invitrogen	BMS204-3TEN	Ten-plate format of the human interleukin-8 ELISA kit. Listed as an available assay format for interleukin-8 measurement.
Laboratory information system	People’s Hospital of Guangxi Zhuang Autonomous Region	Institutional system, not commercially cataloged	Source system for HBP, CRP, procalcitonin, lactate, albumin, complete blood count, coagulation variables, liver and kidney function variables, interleukin-6, and interleukin-8 when available.
Laboratory information system extraction specification	Study investigators	LIS extraction specification version 1.0	Investigator-developed extraction specification defining biomarker variables, blood draw time, report time, sampling windows, unit checks, and field mapping from the laboratory information system.
Laboratory standard operating procedure	People’s Hospital of Guangxi Zhuang Autonomous Region, central laboratory	Laboratory SOP version 2022.1	Version-controlled internal protocol for routine biomarker processing, assay operation, reportable-range rules, internal quality control, and result release.
PreciControl Multimarker	Roche Diagnostics	5341787190	Quality-control material listed for Roche Elecsys IL-6 assay workflows.
pROC R package	CRAN / R package authors	Version 1.18.5	R package used for receiver operating characteristic curve analysis, AUC estimation, confidence intervals, and DeLong tests.
R statistical software	R Foundation for Statistical Computing	Version 4.3.2	Statistical computing environment used for all analyses.
rms R package	CRAN / R package authors	Version 6.8-0	R package used for regression modeling, calibration plots, calibration intercept and slope, and model performance assessment.
Statistical analysis plan	Study investigators	Analysis specification version 1.0	Prespecified statistical analysis plan defining endpoint coding, descriptive analyses, receiver operating characteristic analysis, regression models, reclassification metrics, and sensitivity analyses.
survival R package	CRAN / R package authors	Version 3.5-7	R package used for Cox proportional hazards regression and survival-related model checking.