Sepsis-related haemostatic disorders, especially disseminated intravascular coagulation (DIC), substantially impact morbidity and mortality; nevertheless, early diagnosis is difficult due to the absence of precise biomarkers. This study assesses novel biomarkers that connect immunological dysregulation and coagulation pathways, presenting opportunities for prompt detection and enhanced therapy. Proinflammatory cytokines (IL-6, TNF-α) and D-dimer are fundamental indicators, however they lack specificity. Emerging biomarkers such as presepsin (sCD14-ST), indicative of bacterial phagocytosis and predictive of coagulopathy within 24 hours, and interleukin-27 (IL-27), possessing both pro- and anti-inflammatory characteristics, provide enhanced diagnostic precision compared to traditional markers. Angiopoietin-2 (Ang-2), a principal modulator of endothelial dysfunction, exhibits a robust correlation with the risk of disseminated intravascular coagulation (DIC) (OR >5) and death, whereas neutrophil extracellular traps (NETs) and their constituents (e.g., citrullinated histones) establish mechanistic connections between thromboinflammation and organ failure. Neutrophil CD64 (nCD64), which is swiftly increased during bacterial sepsis, provides great specificity (>90%) for the detection of infections. These biomarkers target essential deficiencies in sepsis management, encompassing early diagnosis, dynamic risk stratification, and therapeutic monitoring. Obstacles persist in standardisation and clinical use; nonetheless, including these indicators in multimodal panels or point-of-care systems has the potential to transform sepsis management. Future research should concentrate on substantiating their efficacy in directing specific therapy, such as immunomodulation or anticoagulation, to alleviate sepsis-induced coagulopathy and enhance outcomes.
References
[1]
Salomão, R., Ferreira, B.L., Salomão, M.C., Santos, S.S., Azevedo, L.C.P. and Brunialti, M.K.C. (2019) Sepsis: Evolving Concepts and Challenges. Brazilian Journal of Medical and Biological Research, 52, e8595. https://doi.org/10.1590/1414-431x20198595
[2]
Mukhtar, A. (2022) Sepsis and Sepsis Syndrome. https://www.researchgate.net/publication/362580595_Sepsis_and_sepsis_syndrome
[3]
Cecconi, M., Evans, L., Levy, M. and Rhodes, A. (2018) Sepsis and Septic Shock. The Lancet, 392, 75-87. https://doi.org/10.1016/s0140-6736(18)30696-2
[4]
Chousterman, B.G., Swirski, F.K. and Weber, G.F. (2017) Cytokine Storm and Sepsis Disease Pathogenesis. Seminars in Immunopathology, 39, 517-528. https://doi.org/10.1007/s00281-017-0639-8
[5]
Kornblith, L.Z., Moore, H.B. and Cohen, M.J. (2019) Trauma-Induced Coagulopathy: The Past, Present, and Future. Journal of Thrombosis and Haemostasis, 17, 852-862. https://doi.org/10.1111/jth.14450
[6]
Deng, M., Tang, Y., Li, W., Wang, X., Zhang, R., Zhang, X., et al. (2018) The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis. Immunity, 49, 740-753.e7. https://doi.org/10.1016/j.immuni.2018.08.016
[7]
Iba, T., Levy, J.H., Yamakawa, K., Thachil, J., Warkentin, T.E. and Levi, M. (2019) Proposal of a Two-Step Process for the Diagnosis of Sepsis-Induced Disseminated Intravascular Coagulation. Journal of Thrombosis and Haemostasis, 17, 1265-1268. https://doi.org/10.1111/jth.14482
[8]
Iba, T., Levi, M., Thachil, J., Helms, J., Scarlatescu, E. and Levy, J.H. (2023) Communication from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis on Sepsis-Induced Coagulopathy in the Management of Sepsis. Journal of Thrombosis and Haemostasis, 21, 145-153. https://doi.org/10.1016/j.jtha.2022.10.022
[9]
Curtiaud, A., Iba, T., Angles-Cano, E., Meziani, F. and Helms, J. (2025) Biomarkers of Sepsis-Induced Coagulopathy: Diagnostic Insights and Potential Therapeutic Implications. Annals of Intensive Care, 15, Article No. 12. https://doi.org/10.1186/s13613-025-01434-2
[10]
Chaudhry, H., Zhou, J., Zhong, Y., Ali, M.M., McGuire, F., Nagarkatti, P.S. and Nagarkatti, M. (2013) Role of Cytokines as a Double-Edged Sword in Sepsis. In Vivo, 27, 669-684.
[11]
Rubio, I., Osuchowski, M.F., Shankar-Hari, M., Skirecki, T., Winkler, M.S., Lachmann, G., et al. (2019) Current Gaps in Sepsis Immunology: New Opportunities for Translational Research. The Lancet Infectious Diseases, 19, e422-e436. https://doi.org/10.1016/s1473-3099(19)30567-5
[12]
Nierhaus, A., Klatte, S., Linssen, J., Eismann, N.M., Wichmann, D., Hedke, J., et al. (2013) Revisiting the White Blood Cell Count: Immature Granulocytes Count as a Diagnostic Marker to Discriminate between SIRS and Sepsis—A Prospective, Observational Study. BMC Immunology, 14, Article No. 8. https://doi.org/10.1186/1471-2172-14-8
[13]
Cox, L.E., Walstein, K., Völlger, L., Reuner, F., Bick, A., Dötsch, A., et al. (2020) Neutrophil Extracellular Trap Formation and Nuclease Activity in Septic Patients. BMC Anesthesiology, 20, Article No. 15. https://doi.org/10.1186/s12871-019-0911-7
[14]
Mao, J., Zhang, J., Cheng, W., Chen, J. and Cui, N. (2021) Effects of Neutrophil Extracellular Traps in Patients with Septic Coagulopathy and Their Interaction with Autophagy. Frontiers in Immunology, 12, Article 757041. https://doi.org/10.3389/fimmu.2021.757041
[15]
Akinosoglou, K., Theodoraki, S., Xanthopoulou, I., Perperis, A., Gkavogianni, T., Pistiki, A., et al. (2017) Platelet Reactivity in Sepsis Syndrome: Results from the PRESS Study. European Journal of Clinical Microbiology & Infectious Diseases, 36, 2503-2512. https://doi.org/10.1007/s10096-017-3093-6
[16]
Parker, W.A. and Storey, R.F. (2020) Antithrombotic Therapy for Patients with Chronic Coronary Syndromes. Heart, 107, 925-933. https://doi.org/10.1136/heartjnl-2020-316914
[17]
Ince, C., Mayeux, P.R., Nguyen, T., Gomez, H., Kellum, J.A., Ospina-Tascón, G.A., et al. (2016) The Endothelium in Sepsis. Shock, 45, 259-270. https://doi.org/10.1097/shk.0000000000000473
[18]
Giustozzi, M., Ehrlinder, H., Bongiovanni, D., Borovac, J.A., Guerreiro, R.A., Gąsecka, A., et al. (2021) Coagulopathy and Sepsis: Pathophysiology, Clinical Manifestations and Treatment. Blood Reviews, 50, Article ID: 100864. https://doi.org/10.1016/j.blre.2021.100864
[19]
Houck, K.L., Yuan, H., Tian, Y., Solomon, M., Cramer, D., Liu, K., et al. (2019) Physical Proximity and Functional Cooperation of Glycoprotein 130 and Glycoprotein VI in Platelet Membrane Lipid Rafts. Journal of Thrombosis and Haemostasis, 17, 1500-1510. https://doi.org/10.1111/jth.14525
[20]
Thomas, M.R., Outteridge, S.N., Ajjan, R.A., Phoenix, F., Sangha, G.K., Faulkner, R.E., et al. (2015) Platelet P2Y12 Inhibitors Reduce Systemic Inflammation and Its Prothrombotic Effects in an Experimental Human Model. Arteriosclerosis, Thrombosis, and Vascular Biology, 35, 2562-2570. https://doi.org/10.1161/atvbaha.115.306528
[21]
Barichello, T., Generoso, J.S., Singer, M. and Dal-Pizzol, F. (2022) Biomarkers for Sepsis: More than Just Fever and Leukocytosis—A Narrative Review. Critical Care, 26, Article No. 14. https://doi.org/10.1186/s13054-021-03862-5
[22]
Cone, S.J., Fuquay, A.T., Litofsky, J.M., Dement, T.C., Carolan, C.A. and Hudson, N.E. (2020) Inherent Fibrin Fiber Tension Propels Mechanisms of Network Clearance during Fibrinolysis. Acta Biomaterialia, 107, 164-177. https://doi.org/10.1016/j.actbio.2020.02.025
[23]
Biron, B.M., Ayala, A. and Lomas-Neira, J.L. (2015) Biomarkers for Sepsis: What Is and What Might Be? Biomarker Insights, 10, 7-17. https://doi.org/10.4137/bmi.s29519
[24]
Cho, S. and Choi, J. (2014) Biomarkers of Sepsis. Infection & Chemotherapy, 46, 1-12. https://doi.org/10.3947/ic.2014.46.1.1
[25]
Gregoriano, C., Heilmann, E., Molitor, A. and Schuetz, P. (2020) Role of Procalcitonin Use in the Management of Sepsis. Journal of Thoracic Disease, 12, S5-S15. https://doi.org/10.21037/jtd.2019.11.63
[26]
Self, W.H., Balk, R.A., Grijalva, C.G., Williams, D.J., Zhu, Y., Anderson, E.J., et al. (2017) Procalcitonin as a Marker of Etiology in Adults Hospitalized with Community-Acquired Pneumonia. Clinical Infectious Diseases, 65, 183-190. https://doi.org/10.1093/cid/cix317
[27]
Yunus, I., Fasih, A. and Wang, Y. (2018) The Use of Procalcitonin in the Determination of Severity of Sepsis, Patient Outcomes and Infection Characteristics. PLOS ONE, 13, e0206527. https://doi.org/10.1371/journal.pone.0206527
[28]
Gupta, S., Jaswani, P., Sharma, R.K., Agrawal, S., Prasad, N., Sahu, C., et al. (2019) Procalcitonin as a Diagnostic Biomarker of Sepsis: A Tertiary Care Centre Experience. Journal of Infection and Public Health, 12, 323-329. https://doi.org/10.1016/j.jiph.2018.11.004
[29]
Anush, M.M., Ashok, V.K., Sarma, R.I. and Pillai, S.K. (2019) Role of C-Reactive Protein as an Indicator for Determining the Outcome of Sepsis. Indian Journal of Critical Care Medicine, 23, 11-14.
[30]
Dhakad, V., Trikha, S., Singh, N. and Kansal, A. (2019) Sequential C-Reactive Protein: A Cheap and a Valuable Biomarker in Patients with Sepsis. International Journal of Research in Medical Sciences, 7, 1837-1841. https://doi.org/10.18203/2320-6012.ijrms20191687
[31]
Li, X., Li, T., Fu, H., Lin, F., Li, C., Bai, Q., et al. (2025) C-Reactive Protein to Platelet Ratio as an Early Biomarker in Differentiating Neonatal Late-Onset Sepsis in Neonates with Pneumonia. Scientific Reports, 15, Article No. 10760. https://doi.org/10.1038/s41598-025-94845-x
[32]
Bhol, N.K., Bhanjadeo, M.M., Singh, A.K., Dash, U.C., Ojha, R.R., Majhi, S., et al. (2024) The Interplay between Cytokines, Inflammation, and Antioxidants: Mechanistic Insights and Therapeutic Potentials of Various Antioxidants and Anti-Cytokine Compounds. Biomedicine & Pharmacotherapy, 178, Article ID: 117177. https://doi.org/10.1016/j.biopha.2024.117177
[33]
Frimpong, A., Owusu, E.D.A., Amponsah, J.A., Obeng-Aboagye, E., Puije, W.V.D., Frempong, A.F., et al. (2022) Cytokines as Potential Biomarkers for Differential Diagnosis of Sepsis and Other Non-Septic Disease Conditions. Frontiers in Cellular and Infection Microbiology, 12, Article 901433. https://doi.org/10.3389/fcimb.2022.901433
[34]
Gharamti, A.A., Samara, O., Monzon, A., Montalbano, G., Scherger, S., DeSanto, K., et al. (2022) Proinflammatory Cytokines Levels in Sepsis and Healthy Volunteers, and Tumor Necrosis Factor-α Associated Sepsis Mortality: A Systematic Review and Meta-Analysis. Cytokine, 158, Article ID: 156006. https://doi.org/10.1016/j.cyto.2022.156006
[35]
Markanday, A. (2015) Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians. Open Forum Infectious Diseases, 2, ofv098. https://doi.org/10.1093/ofid/ofv098
[36]
Nehring, S.M., Patel, B.C. and Goyal, A. (2023) C Reactive Protein (CRP): Clinical Relevance and Interpretation. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK441843/
[37]
Lee, H. (2013) Procalcitonin as a Biomarker of Infectious Diseases. The Korean Journal of Internal Medicine, 28, 285-291. https://doi.org/10.3904/kjim.2013.28.3.285
[38]
Doganyigit, Z., Eroglu, E. and Akyuz, E. (2022) Inflammatory Mediators of Cytokines and Chemokines in Sepsis: From Bench to Bedside. Human & Experimental Toxicology, 41, 1-11. https://doi.org/10.1177/09603271221078871
[39]
Schulte, W., Bernhagen, J. and Bucala, R. (2013) Cytokines in Sepsis: Potent Immunoregulators and Potential Therapeutic Targets—An Updated View. Mediators of Inflammation, 2013, Article ID: 165974. https://doi.org/10.1155/2013/165974
[40]
Ding, H., Wang, G., Yu, Z., Sun, H. and Wang, L. (2022) Role of Interferon-γ (IFN-γ) and IFN-γ Receptor 1/2 (IFNγR1/2) in Regulation of Immunity, Infection, and Cancer Development: IFN-γ-Dependent or Independent Pathway. Biomedicine & Pharmacotherapy, 155, Article ID: 113683. https://doi.org/10.1016/j.biopha.2022.113683
[41]
Olad, E., Sedighi, I., Mehrvar, A., Tashvighi, M., Fallahazad, V., Hedayatiasl, A., et al. (2014) Presepsin (Scd14) as a Marker of Serious Bacterial Infections in Chemotherapy Induced Severe Neutropenia. Iranian Journal of Pediatrics, 24, 715-722. https://pmc.ncbi.nlm.nih.gov/articles/PMC4442833/
[42]
Margetic, S. (2012) Inflammation and Hemostasis. Biochemia Medica, 22, 49-62. https://doi.org/10.11613/bm.2012.006
[43]
Megha, K., Joseph, X., Akhil, V. and Mohanan, P. (2021) Cascade of Immune Mechanism and Consequences of Inflammatory Disorders. Phytomedicine, 91, Article ID: 153712. https://doi.org/10.1016/j.phymed.2021.153712
[44]
Adam, S.S., Key, N.S. and Greenberg, C.S. (2009) D-Dimer Antigen: Current Concepts and Future Prospects. Blood, 113, 2878-2887. https://doi.org/10.1182/blood-2008-06-165845
[45]
Tripodi, A. (2011) D-Dimer Testing in Laboratory Practice. Clinical Chemistry, 57, 1256-1262. https://doi.org/10.1373/clinchem.2011.166249
[46]
Joshi, D., Bontekoe, E., Rondina, M., Middleton, E., Blair, A., Siddiqui, F., et al. (2020) Altered Coagulation Parameters and D-Dimer Measurements in Sepsis Are Useful in Scoring the Risk Stratification. The FASEB Journal, 34, 1. https://doi.org/10.1096/fasebj.2020.34.s1.04208
[47]
Williams, B., Zou, L., Pittet, J. and Chao, W. (2024) Sepsis-induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesthesia & Analgesia, 138, 696-711. https://doi.org/10.1213/ane.0000000000006888
[48]
Balal, A., M. Obeidat, A., Y. Fadul, K., Sati, W., M.I. Ahmed, S., Elgassim, M., et al. (2024) Sepsis-Induced Coagulopathy: From Pathophysiology to Patient Care. In: Shaikh, N., Ed., Septic Shock—From Pathophysiology to Patient Care, IntechOpen. https://doi.org/10.5772/intechopen.1007341
[49]
Unar, A., Bertolino, L., Patauner, F., Gallo, R. and Durante-Mangoni, E. (2023) Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview. Cells, 12, Article 2120. https://doi.org/10.3390/cells12172120
[50]
Adelborg, K., Larsen, J.B. and Hvas, A. (2021) Disseminated Intravascular Coagulation: Epidemiology, Biomarkers, and Management. British Journal of Haematology, 192, 803-818. https://doi.org/10.1111/bjh.17172
[51]
Crochemore, T., Scarlatescu, E., Görlinger, K., Rocha, M.D.P., Carlos de Campos Guerra, J., Campêlo, D.H.C., et al. (2024) Fibrinogen Contribution to Clot Strength in Patients with Sepsis and Hematologic Malignancies and Thrombocytopenia—A Prospective, Single-Center, Analytical, Cross-Sectional Study. Research and Practice in Thrombosis and Haemostasis, 8, Article ID: 102362. https://doi.org/10.1016/j.rpth.2024.102362
[52]
Yang, R. and Moosavi, L. (2024) Prothrombin Time. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK544269/
[53]
Ito, T. and Maruyama, I. (2011) Thrombomodulin: Protectorate God of the Vasculature in Thrombosis and Inflammation. Journal of Thrombosis and Haemostasis, 9, 168-173. https://doi.org/10.1111/j.1538-7836.2011.04319.x
[54]
Starikova, E.A., Mammedova, J.T., Rubinstein, A.A., Sokolov, A.V. and Kudryavtsev, I.V. (2025) Activation of the Coagulation Cascade as a Universal Danger Sign. Current Issues in Molecular Biology, 47, Article 108. https://doi.org/10.3390/cimb47020108
[55]
Semeraro, N., Ammollo, C.T., Semeraro, F. and Colucci, M. (2010) Sepsis-Associated Disseminated Intravascular Coagulation and Thromboembolic Disease. Mediterranean Journal of Hematology and Infectious Diseases, 2, e2010024. https://doi.org/10.4084/mjhid.2010.024
[56]
Senst, B., Tadi, P., Basit, H. and Jan, A. (2023) Hypercoagulability. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK538251/
[57]
Yamada, S. and Asakura, H. (2024) How We Interpret Thrombosis with Thrombocytopenia Syndrome? International Journal of Molecular Sciences, 25, Article 4956. https://doi.org/10.3390/ijms25094956
[58]
Vincent, J., Sakr, Y., Singer, M., Martin-Loeches, I., Machado, F.R., Marshall, J.C., et al. (2020) Prevalence and Outcomes of Infection among Patients in Intensive Care Units in 2017. JAMA, 323, 1478-1487. https://doi.org/10.1001/jama.2020.2717
[59]
Baldirà, J., Ruiz-Rodríguez, J.C., Ruiz-Sanmartin, A., Chiscano, L., Cortes, A., Sistac, D.Á., et al. (2023) Use of Biomarkers to Improve 28-Day Mortality Stratification in Patients with Sepsis and SOFA ≤ 6. Biomedicines, 11, Article 2149. https://doi.org/10.3390/biomedicines11082149
[60]
Limongi, D., D’Agostini, C. and Ciotti, M. (2016) New Sepsis Biomarkers. Asian Pacific Journal of Tropical Biomedicine, 6, 516-519. https://doi.org/10.1016/j.apjtb.2016.04.005
[61]
Velissaris, D., Zareifopoulos, N., Karamouzos, V., Karanikolas, E., Pierrakos, C., Koniari, I., et al. (2021) Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis. Cureus, 13, e15019. https://doi.org/10.7759/cureus.15019
[62]
Giavarina, D. and Carta, M. (2015) Determination of Reference Interval for Presepsin, an Early Marker for Sepsis. Biochemia Medica, 25, 64-68. https://doi.org/10.11613/bm.2015.007
[63]
Stankovic, S. (2022) Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis. IntechOpen eBooks. https://www.intechopen.com/chapters/83909
[64]
Zhang, X., Liu, D., Liu, Y., Wang, R. and Xie, L. (2015) The Accuracy of Presepsin (sCD14-ST) for the Diagnosis of Sepsis in Adults: A Meta-Analysis. Critical Care, 19, Article No. 323. https://doi.org/10.1186/s13054-015-1032-4
[65]
de Guadiana Romualdo, L.G., Torrella, P.E., Acebes, S.R., Otón, M.D.A., Sánchez, R.J., Holgado, A.H., et al. (2017) Diagnostic Accuracy of Presepsin (sCD14-ST) as a Biomarker of Infection and Sepsis in the Emergency Department. Clinica Chimica Acta, 464, 6-11. https://doi.org/10.1016/j.cca.2016.11.003
[66]
Xiao, H., Zhang, H., Wang, G., Wang, Y., Tan, Z., Sun, X., et al. (2024) Comparison among Presepsin, Procalcitonin, And C-Reactive Protein in Predicting Blood Culture Positivity and Pathogen in Sepsis Patients. Shock, 61, 387-394. https://pubmed.ncbi.nlm.nih.gov/37878488/
[67]
Wu, C., Lan, H., Han, S., Chaou, C., Yeh, C., Liu, S., et al. (2017) Comparison of Diagnostic Accuracy in Sepsis between Presepsin, Procalcitonin, and C-Reactive Protein: A Systematic Review and Meta-Analysis. Annals of Intensive Care, 7, Article No. 91. https://doi.org/10.1186/s13613-017-0316-z
[68]
Shimoyama, Y., Kadono, N. and Umegaki, O. (2024) Presepsin Is a More Useful Predictor of Septic AKI and ARDS for Very-Old Sepsis Patients than for Young Sepsis Patients in ICUs: A Pilot Study. BMC Research Notes, 17, Article No. 53. https://doi.org/10.1186/s13104-024-06719-6
[69]
Formenti, P., Gotti, M., Palmieri, F., Pastori, S., Roccaforte, V., Menozzi, A., et al. (2024) Presepsin in Critical Illness: Current Knowledge and Future Perspectives. Diagnostics, 14, Article 1311. https://doi.org/10.3390/diagnostics14121311
[70]
Fan, J., Zhang, Y., Zheng, D., Zhang, M., Liu, H., He, M., et al. (2020) IL-27 Is Elevated in Sepsis with Acute Hepatic Injury and Promotes Hepatic Damage and Inflammation in the CLP Model. Cytokine, 127, Article ID: 154936. https://doi.org/10.1016/j.cyto.2019.154936
[71]
Wang, Y., Zhao, J., Yao, Y., Zhao, D. and Liu, S. (2021) Interleukin‐27 as a Diagnostic Biomarker for Patients with Sepsis: A Meta-Analysis. BioMed Research International, 2021, Article ID: 5516940. https://doi.org/10.1155/2021/5516940
[72]
Hanna, W.J., Berrens, Z., Langner, T., Lahni, P. and Wong, H.R. (2015) Interleukin-27: A Novel Biomarker in Predicting Bacterial Infection among the Critically Ill. Critical Care, 19, Article No. 378. https://doi.org/10.1186/s13054-015-1095-2
[73]
Bosmann, M. and Ward, P.A. (2013) Modulation of Inflammation by Interleukin-27. Journal of Leukocyte Biology, 94, 1159-1165. https://doi.org/10.1189/jlb.0213107
[74]
Annamanedi, M., Povroznik, J.M. and Robinson, C.M. (2025) STAT-3 Is Necessary for Il-27-Mediated Macrophage Suppression but Does Not Represent a Therapeutic Target for E. coli-Induced Neonatal Sepsis. Microbiology Spectrum, 13, e02211-24. https://doi.org/10.1128/spectrum.02211-24
[75]
Patel, P., Walborn, A., Rondina, M., Fareed, J. and Hoppensteadt, D. (2019) Markers of Inflammation and Infection in Sepsis and Disseminated Intravascular Coagulation. Clinical and Applied Thrombosis/Hemostasis, 25, 1-6. https://doi.org/10.1177/1076029619843338
[76]
Gao, F., Yang, Y., Feng, X., Fan, T., Jiang, L., Guo, R., et al. (2016) Interleukin-27 Is Elevated in Sepsis-Induced Myocardial Dysfunction and Mediates Inflammation. Cytokine, 88, 1-11. https://doi.org/10.1016/j.cyto.2016.08.006
[77]
Rautela, A., Garg, J., Agarwal, J., Raj, N., Das, A. and Sen, M. (2024) Evaluation of a Novel Serum Marker, Interleukin 27, in Comparison to Procalcitonin and C-Reactive Protein in the Diagnosis of Early-Onset Neonatal Sepsis in a Tertiary Care Center in North India. International Journal of Critical Illness and Injury Science, 14, 181-187. https://doi.org/10.4103/ijciis.ijciis_45_24
[78]
Statz, S., Sabal, G., Walborn, A., Williams, M., Hoppensteadt, D., Mosier, M., et al. (2018) Angiopoietin 2 Levels in the Risk Stratification and Mortality Outcome Prediction of Sepsis-Associated Coagulopathy. Clinical and Applied Thrombosis/Hemostasis, 24, 1223-1233. https://doi.org/10.1177/1076029618786029
[79]
Zhuo, M., Fu, S., Chi, Y., Li, X., Li, S., Ma, X., et al. (2024) Angiopoietin-2 as a Prognostic Biomarker in Septic Adult Patients: A Systemic Review and Meta-Analysis. Annals of Intensive Care, 14, Article No. 169. https://doi.org/10.1186/s13613-024-01393-0
[80]
Ma, S., Zhao, M., Wang, K., Yue, Y., Sun, R., Zhang, R., et al. (2020) Association of Ang-2, vWF, and EVLWI with Risk of Mortality in Sepsis Patients with Concomitant ARDS: A Retrospective Study. Journal of the Formosan Medical Association, 119, 950-956. https://doi.org/10.1016/j.jfma.2019.11.005
[81]
Szederjesi, J., Almasy, E., Lazar, A., HuȚanu, A. and Georgescu, A. (2015) The Role of Angiopoietine-2 in the Diagnosis and Prognosis of Sepsis. The Journal of Critical Care Medicine, 1, 18-23. https://doi.org/10.1515/jccm-2015-0004
[82]
Thanh Duyen, L.T., Manh, B.V., Phuong Thao, T.T., Khanh, L.V., Linh Trang, B.N., Giang, N.T., et al. (2022) Prognostic Significance of the Angiopoietin-2 for Early Prediction of Septic Shock in Severe Sepsis Patients. Future Science OA, 8, FSO825. https://doi.org/10.2144/fsoa-2022-0077
[83]
Smadja, D.M., Guerin, C.L., Chocron, R., Yatim, N., Boussier, J., Gendron, N., et al. (2020) Angiopoietin-2 as a Marker of Endothelial Activation Is a Good Predictor Factor for Intensive Care Unit Admission of COVID-19 Patients. Angiogenesis, 23, 611-620. https://doi.org/10.1007/s10456-020-09730-0
[84]
Robbin, V., Bansal, V., Vellanki, K., Siddiqui, F., Hoppensteadt-Moorman, D., Fareed, J., et al. (2024) Angiopoietin-2 and Mortality Outcomes in End-Stage Renal Disease with Heart Failure as a Comorbidity. Clinical and Applied Thrombosis/Hemostasis, 30, 1-5. https://doi.org/10.1177/10760296241305101
[85]
Liu, X., Ma, T., Liu, W., Cai, Q., Wang, L., Song, H., et al. (2018) Sustained Increase in Angiopoietin-2, Heparin-Binding Protein, and Procalcitonin Is Associated with Severe Sepsis. Journal of Critical Care, 45, 14-19. https://doi.org/10.1016/j.jcrc.2018.01.010
[86]
Lymperopoulou, K., Velissaris, D., Kotsaki, A., Antypa, E., Georgiadou, S., Tsaganos, T., et al. (2015) Angiopoietin-2 Associations with the Underlying Infection and Sepsis Severity. Cytokine, 73, 163-168. https://doi.org/10.1016/j.cyto.2015.01.022
[87]
Le Cras, T.D., Mobberley-Schuman, P.S., Broering, M., Fei, L., Trenor, C.C. and Adams, D.M. (2016) Angiopoietins as Serum Biomarkers for Lymphatic Anomalies. Angiogenesis, 20, 163-173. https://doi.org/10.1007/s10456-016-9537-2
[88]
Delabranche, X., Stiel, L., Severac, F., Galoisy, A., Mauvieux, L., Zobairi, F., et al. (2017) Evidence of Netosis in Septic Shock-Induced Disseminated Intravascular Coagulation. Shock, 47, 313-317. https://doi.org/10.1097/shk.0000000000000719
[89]
Gong, F., Zheng, X., Zhao, S., Liu, H., Chen, E., Xie, R., et al. (2025) Disseminated Intravascular Coagulation: Cause, Molecular Mechanism, Diagnosis, and Therapy. MedComm, 6, e70058. https://doi.org/10.1002/mco2.70058
[90]
Tsantes, A.G., Parastatidou, S., Tsantes, E.A., Bonova, E., Tsante, K.A., Mantzios, P.G., et al. (2023) Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines. Life, 13, Article 350. https://doi.org/10.3390/life13020350
[91]
Demyanets, S., Stojkovic, S., Mauracher, L., Kopp, C.W., Wojta, J., Thaler, J., et al. (2020) Surrogate Markers of Neutrophil Extracellular Trap Formation Are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting. Journal of Clinical Medicine, 9, Article 304. https://doi.org/10.3390/jcm9020304
[92]
Hawley, K.L., Cruz, A.R., Benjamin, S.J., La Vake, C.J., Cervantes, J.L., LeDoyt, M., et al. (2017) IFNγ Enhances CD64-Potentiated Phagocytosis of Treponema Pallidum Opsonized with Human Syphilitic Serum by Human Macrophages. Frontiers in Immunology, 8, Article 1227. https://doi.org/10.3389/fimmu.2017.01227
[93]
Cao, L., Wang, W., Zhao, L., Li, J., Kong, X., Zhu, Y., et al. (2022) Neutrophil CD64 Index for Diagnosis of Infectious Disease in the Pediatric ICU: A Single-Center Prospective Study. BMC Pediatrics, 22, Article No. 718. https://doi.org/10.1186/s12887-022-03738-9
[94]
Retter, A., Singer, M. and Annane, D. (2025) “The NET Effect”: Neutrophil Extracellular Traps—A Potential Key Component of the Dysregulated Host Immune Response in Sepsis. Critical Care, 29, Article No. 59. https://doi.org/10.1186/s13054-025-05283-0
[95]
Pham, H.M., Nguyen, D.L.M., Duong, M.C., Tran, L.T. and Pham, T.T.N. (2023) Diagnostic Value of Neutrophil CD64 in Sepsis Patients in the Intensive Care Unit: A Cross-Sectional Study. Diagnostics, 13, Article 1427. https://doi.org/10.3390/diagnostics13081427
[96]
Pradhan, R., Jain, P., Paria, A., Saha, A., Sahoo, J., Sen, A., et al. (2015) Ratio of Neutrophilic CD64 and Monocytic HLA-DR: A Novel Parameter in Diagnosis and Prognostication of Neonatal Sepsis. Cytometry Part B: Clinical Cytometry, 90, 295-302. https://doi.org/10.1002/cyto.b.21244
[97]
Hoffmann, J.J.M.L. (2009) Neutrophil CD64: A Diagnostic Marker for Infection and Sepsis. Clinical Chemistry and Laboratory Medicine, 47, 903-916. https://doi.org/10.1515/cclm.2009.224
[98]
Gurjar, M., Ajmani, S. and Agarwal, V. (2018) State of Globe: Neutrophil CD64: Is It a Reliable Biomarker for Sepsis? Journal of Global Infectious Diseases, 10, 33-34. https://doi.org/10.4103/jgid.jgid_95_17
[99]
Agarwal, V., Poddar, B., Gurjar, M., Mishra, P., Azim, A., Patnaik, R., et al. (2024) Serial Trend of Neutrophil CD64, C-Reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/septic Shock: A Prospective Observational Study from a Tertiary Care ICU. Indian Journal of Critical Care Medicine, 28, 777-784. https://doi.org/10.5005/jp-journals-10071-24777
[100]
Pierrakos, C., Velissaris, D., Bisdorff, M., Marshall, J.C. and Vincent, J. (2020) Biomarkers of Sepsis: Time for a Reappraisal. Critical Care, 24, Article No. 287. https://doi.org/10.1186/s13054-020-02993-5
[101]
Wu, J., Hu, L., Zhang, G., Wu, F. and He, T. (2015) Accuracy of Presepsin in Sepsis Diagnosis: A Systematic Review and Meta-Analysis. PLOS ONE, 10, e0133057. https://doi.org/10.1371/journal.pone.0133057
[102]
Llitjos, J., Carrol, E.D., Osuchowski, M.F., Bonneville, M., Scicluna, B.P., Payen, D., et al. (2024) Enhancing Sepsis Biomarker Development: Key Considerations from Public and Private Perspectives. Critical Care, 28, Article No. 238. https://doi.org/10.1186/s13054-024-05032-9
