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

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.

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

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.

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.

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.

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.