Ефекат раног нивоа серумског протеина који везује хепарин (ХБП) на појаву сепсе код пацијената са тешким опекотинама

HBP levels on occurrence of sepsis in patients with severe burns

  • Lihan Xiang Универзитет за кинеску медицину у Џеђијангу
  • Guimei Yang Општа болница Иџоу
  • Liming Lou Трећа афилирана болница Кинеског медицинског универзитета Џеђианг
  • Le Lv Друга придружена болница Медицинског факултета Универзитета
  • Liyuan Zheng The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Caixia Zhang Осми медицински центар Генералне болнице НОАК
  • Qian He Осми медицински центар Генералне болнице НОАК

Sažetak


[Objective] To evaluate the expression levels of early serum heparin-binding protein (HBP) in patients with severe burns and investigate its prognostic significance and predictive utility for sepsis development.

[Methods] The clinical data of 52 patients with severe burns who were admitted to our hospital between January 2023 and May 2025 were retrospectively analyzed. General information, including the patient's age, sex, body mass index (BMI), total burn area, and tracheal intubation or tracheotomy, was collected. Within 48 hours of the patient's admission, the patient's blood pressure, white blood cell count, serum procalcitonin (PCT), and serum C reactive protein (CRP) level were measured. The second assessment of acute physiology and chronic health within 48 hours of admission included the results of the sequential organ failure assessment (SOFA) and APACHE II. The patients were separated into two groups on the basis of their conditions at discharge: the nonsurviving group and the surviving group.

[Results] Compared with the nonsepsis group (8.2 ng/mL), the sepsis group had a considerably greater median early serum HBP level (20.8 ng/mL) (P<0.001). The area under the curve (AUC) of HBP for sepsis prediction, according to the ROC curve analysis, was 0.87 (95% CI: 0.82–0.92). The sensitivity was 85.0%, and the specificity was 82.1% at the cutoff value of 14.6 ng/mL. After controlling for confounding variables such burn area and inhalation injury, multivariate logistic regression analysis verified that HBP>14.6 ng/mL was an independent risk factor for the development of sepsis (OR=4.53, 95% CI: 2.67–7.69). According to survival analysis, patients in the high-HBP group had a significantly greater 28-day mortality rate (log-rank P<0.01).
Patients in the death group were older than those in the survival group were, and this difference was statistically significant (P=0.036). The area under the ROC curve (AUC) of the HBP level for predicting patient death during hospitalization was 0.798; its sensitivity and specificity were 88.33% and 70.00%, respectively, for HBP≥147.03 ng/mL. In patients with sepsis following severe burns, the AUC of the HBP level for the prediction of septic shock was 0.789. Its sensitivity and specificity were 90.00% and 63.20%, respectively, when the HBP concentration was greater than 147.03 ng/mL.

[Conclusion] The significantly elevated serum HBP level in patients with severe burns in the early stage is closely related to the risk of sepsis, and it can be used as a sensitive biomarker for early warning of sepsis.

Reference

1.Taha AM, Najah Q, Omar MM, Abouelmagd K, Ali M, Hasan MT, Allam SA, Hamam YA, Arian R, Abd-ElGawad M. Diagnostic and prognostic value of heparin-binding protein in sepsis: A systematic review and meta-analysis. Medicine (Baltimore). 2024 Jun 21;103(25):e38525. doi: 10.1097/MD.0000000000038525. PMID: 38905400; PMCID: PMC11191987.
2.Liu Z, Li X, Chen M, Sun Y, Ma Y, Dong M, Cao L, Ma X. Heparin-binding protein and sepsis-induced coagulopathy: Modulation of coagulation and fibrinolysis via the TGF-β signalling pathway. Thromb Res. 2024 Dec;244:109176. doi: 10.1016/j.thromres.2024.109176. Epub 2024 Oct 14. PMID: 39447256.
3.Tang J, Yuan H, Wu YL, Fu S, Pan XY. The Predictive Value of Heparin-Binding Protein and D-Dimer in Patients with Sepsis. Int J Gen Med. 2023 Jun 6;16:2295-2303. doi: 10.2147/IJGM.S409328. PMID: 37304904; PMCID: PMC10257474.
4.Katsaros K, Renieris G, Safarika A, Adami EM, Gkavogianni T, Giannikopoulos G, Solomonidi N, Halvatzis S, Koutelidakis IM, Tsokos N, Tritzali M, Koutoukas P, Avgoustou C, Vasishta A, Giamarellos-Bourboulis EJ. Heparin Binding Protein for the Early Diagnosis and Prognosis of Sepsis in the Emergency Department: The Prompt Multicenter Study. Shock. 2022 Apr 1;57(4):518-525. doi: 10.1097/SHK.0000000000001900. PMID: 34907118.
5.Xu C, Li J. Tamibarotene targets heparin-binding protein for attenuating lung injury in sepsis. Allergol Immunopathol (Madr). 2023 Jul 1;51(4):124-130. doi: 10.15586/aei.v51i4.900. PMID: 37422788.
6.Han X, Dou Q, Zhu Y, Ling P, Shen YH, Liu J, Zhang Z, Zhou Y, Fan M, Huang SS, Lee CC. Heparin-binding protein-enhanced quick SOFA score improves mortality prediction in sepsis patients. Front Med (Lausanne). 2022 Aug 11;9:926798. doi: 10.3389/fmed.2022.926798. PMID: 36035420; PMCID: PMC9402998.
7.Neumann A. Rapid release of sepsis markers heparin-binding protein and calprotectin triggered by anaerobic cocci poses an underestimated threat. Anaerobe. 2022 Jun;75:102584. doi: 10.1016/j.anaerobe.2022.102584. Epub 2022 May 8. PMID: 35545182.
8.Chen X, Li H, Li J, Liu X, Chen L, Chen C, Yuan J, Tao E. The potential role of heparin-binding protein in neonatal sepsis: research progress. Front Cell Infect Microbiol. 2024 Aug 13;14:1422872. doi: 10.3389/fcimb.2024.1422872. PMID: 39193501; PMCID: PMC11347420.
9.Zuo L, Li X, Wang L, Yuan H, Liao Z, Zhou S, Wu J, Guan X, Liu Y. Heparin-binding protein as a biomarker for the diagnosis of sepsis in the intensive care unit: a retrospective cross-sectional study in China. BMJ Open. 2024 Jun 10;14(6):e078687. doi: 10.1136/bmjopen-2023-078687. PMID: 38858136; PMCID: PMC11168158.
10.Ye K, Lin X, Chen TZ, Wang LH, Liu SX. Heparin-Binding Protein Promotes Acute Lung Injury in Sepsis Mice by Blocking the Aryl Hydrocarbon Receptor Signaling Pathway. J Inflamm Res. 2024 May 13;17:2927-2938. doi: 10.2147/JIR.S454777. PMID: 38764496; PMCID: PMC11100518.
11.Liu P, Chen D, Lou J, Lin J, Huang C, Zou Y, Wong C, Wu H, Yan G, Liu J, Zhou Z, Gao F, Gao L, Long G, Ma L, Dai S, Qu W, Mo L, Shang S, Xu J. Heparin-binding protein as a biomarker of severe sepsis in the pediatric intensive care unit: A multicenter, prospective study. Clin Chim Acta. 2023 Jan 15;539:26-33. doi: 10.1016/j.cca.2022.11.028. Epub 2022 Nov 29. PMID: 36460135.
12.Wu L, Zheng Y, Liu J, Luo R, Wu D, Xu P, Wu D, Li X. Comprehensive evaluation of the efficacy and safety of LPV/r drugs in the treatment of SARS and MERS to provide potential treatment options for COVID-19. Aging (Albany NY). 2021 Apr 20;13(8):10833-10852. doi: 10.18632/aging.202860. Epub 2021 Apr 20. PMID: 33879634; PMCID: PMC8109137.
13.Liu P, Chen D, Lou J, Lin J, Huang C, Zou Y, Wong C, Wu H, Yan G, Liu J, Zhou Z, Gao F, Gao L, Long G, Ma L, Dai S, Qu W, Mo L, Shang S, Xu J. Heparin-binding protein as a biomarker of severe sepsis in the pediatric intensive care unit: A multicenter, prospective study. Clin Chim Acta. 2023 Jan 15;539:26-33. doi: 10.1016/j.cca.2022.11.028. Epub 2022 Nov 29. PMID: 36460135.
14.Zhou X, Cao Y, Huang X, Qiu S, Xiang X, Niu H, Chen L, Wang S, Lin Z, Zhang S. Screening and Application of DNA Aptamers for Heparin-Binding Protein. Molecules. 2024 Apr 10;29(8):1717. doi: 10.3390/molecules29081717. PMID: 38675537; PMCID: PMC11051826.
15.Wu L, Zhong Y, Wu D, Xu P, Ruan X, Yan J, Liu J, Li X. Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis. Biomedicines. 2022 Sep 10;10(9):2248. doi: 10.3390/biomedicines10092248. PMID: 36140350; PMCID: PMC9496572.
16.Fisher J, Kahn F, Wiebe E, Gustafsson P, Kander T, Mellhammar L, Bentzer P, Linder A. The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker. J Innate Immun. 2022;14(5):447-460. doi: 10.1159/000521064. Epub 2021 Dec 29. PMID: 34965528; PMCID: PMC9485916.
17.Yu D, Liu J, Song X, Ao Y, Li X, Han Y. Analysis of the inflammatory storm response and heparin binding protein levels for the diagnosis and prognosis of sepsis-associated encephalopathy. Eur J Med Res. 2025 Feb 18;30(1):116. doi: 10.1186/s40001-025-02369-x. PMID: 39966958; PMCID: PMC11834667.
18.Wu L, Liu Q, Ruan X, Luan X, Zhong Y, Liu J, Yan J, Li X. Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines. 2023 Jun 29;11(7):1861. doi: 10.3390/biomedicines11071861. PMID: 37509501; PMCID: PMC10377220.
19.Xue H, Yu F. Changes in Heparin-Binding Protein, Procalcitonin, and C-Reactive Protein Within the First 72 Hours Predict 28-Day Mortality in Patients Admitted to the Intensive Care Unit with Septic Shock. Med Sci Monit. 2023 Jan 25;29:e938538. doi: 10.12659/MSM.938538. PMID: 36694437; PMCID: PMC9885725.
20.Wu L, Zheng Y, Ruan X, Wu D, Xu P, Liu J, Wu D, Li X. Long-chain noncoding ribonucleic acids affect the survival and prognosis of patients with esophageal adenocarcinoma through the autophagy pathway: construction of a prognostic model. Anticancer Drugs. 2022 Jan 1;33(1):e590-e603. doi: 10.1097/CAD.0000000000001189. PMID: 34338240; PMCID: PMC8670349.
21.Mao Z, Yang W, Gao J, Zhang J, Yang M, Liu H, Kang H, Zhou F. Accuracy of blood heparin-binding protein (HBP) for diagnosis bacteremia in patients with sepsis. Sci Rep. 2025 Feb 17;15(1):5702. doi: 10.1038/s41598-025-89241-4. PMID: 39962104; PMCID: PMC11833100.
22.Feng L, Liu S, Wang J, Gao Y, Xie F, Gong J, Bi S, Yao Z, Li Y, Liu W, Guan C, Zhang M, Wang H, Zheng J. The performance of a combination of heparin-binding protein with other biomarkers for sepsis diagnosis: an observational cohort study. BMC Infect Dis. 2024 Jul 30;24(1):755. doi: 10.1186/s12879-024-09666-6. PMID: 39080540; PMCID: PMC11290073.
23.Wu L, Zhong Y, Yu X, Wu D, Xu P, Lv L, Ruan X, Liu Q, Feng Y, Liu J, Li X. Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research. Anticancer Drugs. 2022 Oct 1;33(9):943-959. doi: 10.1097/CAD.0000000000001319. Epub 2022 Aug 9. PMID: 35946526; PMCID: PMC9481295.
24.Deng JC, Zhao FL, Qiao LN. Value of heparin-binding protein in the diagnosis of severe infection in children: a prospective study. Zhongguo Dang Dai Er Ke Za Zhi. 2022 Jan 15;24(1):85-89. English, Chinese. doi: 10.7499/j.issn.1008-8830.2109057. PMID: 35177181; PMCID: PMC8802393.
25.Xiang Z, Zhang Z, Chen X, Zhang L, Zhou X, Qin Y, Zhao X, Wang Y, Huang B, Tang H. Development and application of amplified luminescent proximity homogeneous assay for quantitation of heparin-binding protein. Anal Biochem. 2022 Nov 15;657:114906. doi: 10.1016/j.ab.2022.114906. Epub 2022 Sep 22. PMID: 36152874.
26.Wu D, Wen T, Li F, Wanyan Z, Ma Z, Ji P, Guo S, Li R, Xue M, Fen K, Song Q. The Value of Heparin Binding Protein in Early Identification of Sepsis-Induced Coagulopathy Disease and Prognosis. Clin Lab. 2025 Jan 1;71(1). doi: 10.7754/Clin.Lab.2024.240714. PMID: 39808151.
27.Johannesson E, Erixon C, Sterner N, Thelaus L, Dardashti A, Nilsson J, Ragnarsson S, Linder A, Zindovic I. Utility of heparin-binding protein following cardiothoracic surgery using cardiopulmonary bypass. Sci Rep. 2023 Dec 7;13(1):21566. doi: 10.1038/s41598-023-48457-y. PMID: 38057352; PMCID: PMC10700527.
28.Olinder J, Stjernqvist MJ, Lindén A, Salomonsson ET, Annborn M, Herwald H, Rydén C. Hepcidin, in contrast to heparin binding protein, does not portend acute kidney injury in patients with community acquired septic shock. PLoS One. 2024 May 2;19(5):e0299257. doi: 10.1371/journal.pone.0299257. PMID: 38696394; PMCID: PMC11065221.
29.Yang W, Dong W. Heparin-binding Protein as a Diagnostic and Prognostic Marker of Infections: A Systematic Review and Meta-analysis. Mediterr J Hematol Infect Dis. 2025 May 1;17(1):e2025029. doi: 10.4084/MJHID.2025.029. PMID: 40375914; PMCID: PMC12081054.
30.Dou QL, Liu J, Zhang W, Wang CW, Gu Y, Li N, Hu R, Hsu WT, Huang AH, Tong HS, Hsu TC, Hsu CA, Xu J, Lee CC. Dynamic changes in heparin-binding protein as a prognostic biomarker for 30-day mortality in sepsis patients in the intensive care unit. Sci Rep. 2022 Jun 24;12(1):10751. doi: 10.1038/s41598-022-14827-1. PMID: 35750778; PMCID: PMC9232494.
31.Zhang J, Cao Y, Shu W, Dong S, Sun Y, Ma X. Neutrophil-derived heparin-binding protein increases endothelial permeability in acute lung injury by promoting TRIM21 and the ubiquitination of P65. Cell Biol Toxicol. 2025 Mar 5;41(1):55. doi: 10.1007/s10565-025-10005-x. PMID: 40045003; PMCID: PMC11882632.
32.And Alternative Medicine EC. Retracted: Diagnostic Value of Serum Heparin Binding Protein, Blood Lactic Acid Combined with hs-CRP in Sepsis and Its Relationship with Prognosis. Evid Based Complement Alternat Med. 2023 Sep 27;2023:9856530. doi: 10.1155/2023/9856530. PMID: 37808126; PMCID: PMC10551257.
33.Liu Z, Chen M, Sun Y, Li X, Cao L, Ma X. Transforming growth factor-β receptor type 2 is required for heparin-binding protein-induced acute lung injury and vascular leakage for transforming growth factor-β/Smad/Rho signaling pathway activation. FASEB J. 2022 Nov;36(11):e22580. doi: 10.1096/fj.202200228RRRRR. PMID: 36189652.
Objavljeno
2025/08/22
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Original paper