Accuracy of Heparin-Binding Protein in Diagnosing Sepsis: A Systematic Review and Meta-Analysis

Abstract

Objectives: Existing studies evaluating the accuracy of heparin-binding protein for the diagnosis of sepsis have been inconsistent. We conducted a systematic review and meta-analysis to assess the totality of current evidence regarding the utility of heparin-binding protein to diagnose sepsis in patients with presumed systemic infection.

Data source: PubMed, Embase, the China National Knowledge infrastructure, and WangFang electronic database were searched from inception to December of 2019.

Study selection: Two independent reviewers identified eligible studies. Cohort and case-control studies, which measured serum levels of heparin-binding protein among adult patients with suspected sepsis, were eligible for inclusion.

Data extraction: Two reviewers independently extracted data elements from the selected studies. A bivariate random-effects meta-analysis model was used to synthesize the prognostic accuracy measures. Risk of bias of studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Data synthesis: We identified 26 studies with 3,868 patients in the meta-analysis. Heparin-binding protein had a pooled sensitivity of 0.85 (95% CI, 0.79-0.90) and a pooled specificity of 0.91 (95% CI, 0.82-0.96) for the diagnosis of sepsis. There was low heterogeneity between the studies (I2 = 12%), and no evidence of publication bias was detected. Heparin-binding protein had a higher sensitivity and specificity when compared with procalcitonin (0.75 [95% CI, 0.62-0.85] and 0.85 [95% CI, 0.73-0.92]) as well as C-reactive protein (0.75 [95% CI, 0.65-0.84] and 0.71 [95% CI, 0.63-0.77]). Serial measurements of heparin-binding protein also showed that heparin-binding protein levels rose significantly at least 24 hours before a diagnosis of sepsis.

Conclusions: The diagnostic ability of heparin-binding protein is favorable, demonstrating both high sensitivity and specificity in predicting progression to sepsis in critically ill patients. Future studies could assess the incremental value that heparin-binding protein may add to a multimodal sepsis identification and prognostication algorithm for critically ill patients.