Plasma ANXA3 shows superior predictive accuracy for sepsis compared to PCT, IL-6, and SOFAProtein levels may help doctors predict life-threatening sepsis faster

Journal of intensive care medicine Published August 3, 2026 Study authors: Lu Hong-Xiang, Ma Cong-Cong, Ma Xin-Xin, Wen Mm Da-Lin, Chen Guo-Sheng, Zhang Fei, Xu Gang, Shi Qing… PubMed ↗ DOI ↗ Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

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Key Takeaway

Note that plasma ANXA3 shows higher predictive accuracy for sepsis than PCT, IL-6, and SOFA score.

This meta-analysis and retrospective cohort study evaluate the utility of Annexin A3 (ANXA3) mRNA expression and plasma levels as biomarkers in patients with sepsis and critically ill patients. The analysis synthesized data from 3241 sepsis patients and 1088 controls for the meta-analysis, alongside a retrospective cohort of 153 critically ill patients.

Key findings indicate that ANXA3 mRNA expression was significantly higher in sepsis patients compared to controls (SMD = 2.01; P < 0.001). Furthermore, plasma ANXA3 demonstrated superior predictive accuracy for sepsis with an AUC of 0.815, outperforming PCT (AUC 0.673), IL-6 (AUC 0.672), and SOFA score (AUC 0.668). In critically ill patients, higher plasma ANXA3 was associated with a higher risk of mortality at 28 days (HR = 2.16; P < 0.05).

While ANXA3 shows potential as a biomarker for predicting sepsis and identifying high-risk patients, the authors note that results regarding 28-day survival were not statistically significant specifically in the sepsis patient subgroup (P > 0.05). The study notes that further evaluation in larger studies is required to confirm these findings.

How this fits prior evidence

This finding addresses a gap in identifying objective biomarkers for early sepsis detection and risk stratification. While previous evidence highlights clinical indicators like skin perfusion parameters, Mottling Score, CRT, and PPI as correlates of mortality, this study suggests plasma ANXA3 may offer superior predictive accuracy compared to standard scores like SOFA or markers like PCT.

Sepsis is a medical emergency where the body's response to infection triggers severe organ damage. Because it moves so quickly, doctors need reliable ways to spot it early. New data suggests that a protein called ANXA3 could be a more reliable warning sign than the markers currently used in many hospitals.

Researchers looked at thousands of patients and found that higher levels of this protein were linked to an increased risk of sepsis in critically ill people. When compared to common tools like procalcitonin or IL-6, the ANXA3 protein showed a better ability to predict who might develop the condition. In some cases, higher levels of the protein were also tied to poorer survival rates over 28 days for patients in critical condition.

While these results are promising, it is important to note that the link between this protein and death was not specifically proven for the sepsis-only group in this study. Because the data comes from a mix of existing records and a meta-analysis, more large-scale studies are needed to confirm exactly how well this protein works as a tool in daily practice.

What this means for you:

The ANXA3 protein shows better accuracy than current markers at predicting sepsis in critically ill patients.

Common questions

What is ANXA3?

ANXA3 is a protein that researchers are studying as a biomarker. A biomarker is a measurable sign that helps doctors identify a condition. In this study, higher levels of ANXA3 were linked to an increased risk of sepsis in critically ill patients.

How does it compare to current tests?

The study found that plasma ANXA3 had a better predictive score than other common markers like procalcitonin, IL-6, and the SOFA score. These are tools doctors currently use to track how sick a patient is during an infection.

Can it tell if a patient will survive?

Higher levels of ANXA3 were associated with poorer 28-day survival in critically ill patients. However, for the specific group of patients who already had sepsis, higher levels did not show a statistically significant link to mortality.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedAug 2026

PMID41544064

View Original Abstract ↓

BackgroundCurrent research indicated the comprehensive investigation of Annexin A3 (ANXA3) in sepsis patients remain uncertain. The aim of this research is to investigate the potential of ANXA3 as a biomarker for prediction of sepsis.MethodsWe performed a meta-analysis utilizing public datasets from Gene Expression Omnibus (GEO) and Array Express database to summarize and evaluate the expression of ANXA3 in sepsis patients. Then, we conducted a retrospective study to explore the role of plasma ANXA3 in 153 critically ill patients. Furthermore, the predictive ability of ANXA3, procalcitonin (PCT), interleukin-6 (IL-6) and Sequential Organ Failure Assessment (SOFA) score for the occurrence of sepsis were evaluated using the Area Under the Curve (AUC).ResultsTotally, the meta-analysis including 3241 sepsis and 1088 controls indicated sepsis patients were with markedly higher levels of ANXA3 mRNA expression (SMD = 2.01(1.54-2.48); P < 0.001). Meanwhile, sepsis deaths (n = 552) were with limited higher expression of ANXA3 mRNA than sepsis survivors (n = 2004) (SMD = 0.14(0.04-0.24); P < 0.01). Furthermore, our results indicated increased plasma ANXA3 on admission were significantly associated with the incidence of sepsis in critically ill patients (OR = 2.41(1.75-3.32), P < 0.001). As a predictive biomarker, plasma ANXA3 resulted in a better AUC 0.815(0.745-0.886) than PCT (0.673(0.584-0.761)) and IL-6 (0.672(0.585-0.759)) and SOFA score (0.668(0.577-0.759)). Additionally, patients with higher plasma ANXA3 had a poorer overall 28-day survival in critically ill patients (HR = 2.16(1.09-4.28); P < 0.05), but not for sepsis patients (HR = 1.63(0.65-4.06); P > 0.05).ConclusionsOur study indicated increased ANXA3 obtained a good predictive ability for sepsis. Meanwhile, plasma ANXA3 was associated with mortality of critically ill patients, but not sepsis patients. The use of ANXA3 as a biomarker in sepsis patients require further evaluation in larger studies.

Plasma ANXA3 shows superior predictive accuracy for sepsis compared to PCT, IL-6, and SOFAProtein levels may help doctors predict life-threatening sepsis faster

How this fits prior evidence

Common questions

Study Details

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Plasma ANXA3 shows superior predictive accuracy for sepsis compared to PCT, IL-6, and SOFAProtein levels may help doctors predict life-threatening sepsis faster

How this fits prior evidence

Common questions

More on Sepsis

Study Details

Intraosseous route for out-of-hospital cardiac arrest linked to lower outcomes than intravenous access

Using a bone needle instead of a vein line lowers survival chances for cardiac arrest patients

Clinical research that matters. Delivered to your inbox.

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