Predictive utility of monocyte chemoattractant Protein-1 (MCP-1) and D-dimer in risk stratification of sepsis: a prospective cohort study

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Abstract

Background. Sepsis is a severe and life-threatening clinical syndrome characterized by a dysregulated host immune response to infection. This maladaptive response promotes widespread endothelial injury and abnormalities in coagulation, often progressing to multi-organ dysfunction and death. Mortality rates remain high, highlighting the urgent need for reliable biomarkers to enable early identification of patients at high risk. Such tools are particularly valuable in low- and middle-income countries (LMICs), where access to advanced diagnostic and therapeutic resources is limited. Monocyte Chemoattractant Protein-1 (MCP-1) is a chemokine that reflects hyperactivation of the innate immune system, while D-dimer indicates activation of coagulation and fibrinolysis. Although both pathways are central to the pathophysiology of sepsis, data evaluating their combined prognostic value in LMIC settings remain scarce. This study aimed to assess the prognostic significance of MCP-1 and D-dimer, both individually and in combination, for predicting 28-day mortality in patients with sepsis. Materials and methods. We conducted a prospective cohort study involving 83 adult patients with newly diagnosed sepsis at Dr. Saiful Anwar General Hospital, Malang, Indonesia. Serum MCP-1 levels were measured using enzyme-linked immunosorbent assay (ELISA), and plasma D-dimer levels were determined by immunoturbidimetry at the time of diagnosis. Patients were followed for 28 days, and survival outcomes were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results. Among the 83 participants, 58 patients (70%) died within 28 days. Non-survivors demonstrated significantly higher MCP-1 and D-dimer levels compared with survivors. An MCP-1 concentration ≥ 123.03 pg/mL was strongly associated with increased mortality (HR 2.664, p = 0.005). Elevated D-dimer (≥ 43.5 mg/L FEU) showed a weaker individual association, but when combined with MCP-1, predictive accuracy for mortality was significantly enhanced (HR 3.986, p = 0.037). Conclusion. The concurrent elevation of MCP-1 and D-dimer identifies patients with sepsis who are at markedly increased risk of death. These findings support the potential utility of integrating inflammatory and coagulation biomarkers for early risk stratification. Moreover, they highlight the central role of the inflammation–coagulation axis in sepsis pathophysiology, with particular relevance for clinical practice in resource-limited settings.

About the authors

Agustin Iskandar

Universitas Brawijaya; Dr. Saiful Anwar General Hospital

Author for correspondence.
Email: agustin_almi@ub.ac.id

PhD, Clinical Pathologist, Associate Profesor, Department of Clinical Pathology, Faculty of Medicine

Indonesia, Malang; Malang

S. Fathonah

Universitas Brawijaya; Dr. Saiful Anwar General Hospital

Email: agustin_almi@ub.ac.id

Clinical Pathologist, Lecturer, Department of Clinical Pathology

Indonesia, Malang; Malang

M. Soraya

Universitas Brawijaya; Dr. Saiful Anwar General Hospital; Ulin General Hospital

Email: agustin_almi@ub.ac.id

Clinical Pathologist, Department of Clinical Pathology, Faculty of Medicine, Clinical Pathologist, Department of Clinical Pathology

Indonesia, Malang; Malang; Banjarmasin

N. N. Lova

Indonesian Doctor Association

Email: agustin_almi@ub.ac.id

General Practitioner, Member of Indonesian Doctor Association

Indonesia, Malang

References

  1. Bozza F.A., Salluh J.I., Japiassu A.M., Soares M., Assis E.F., Gomes R.N., Bozza M.T., Castro-Faria-Neto H.C., Bozza P.T. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit. Care, 2007, vol. 11, no. 2: R49. doi: 10.1186/cc5783
  2. Chen Z., Li C., Yu J. Monocyte chemoattractant protein-1 as a potential marker for patients with sepsis: a systematic review and meta-analysis. Front. Med. (Lausanne), 2023, vol. 10: 1217784. doi: 10.3389/fmed.2023.1217784
  3. Chousterman B.G., Swirski F.K., Weber G.F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathol., 2017, vol. 39, no. 5, pp. 517–528. doi: 10.1007/s00281-017-0639-8
  4. Deshmane S.L., Kremlev S., Amini S., Sawaya B.E. Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon Cytokine Res., 2009, vol. 29, no. 6, pp. 313–326. doi: 10.1089/jir.2008.0027
  5. Ding M., Li M., Yang H. Clinical diagnostic value of combined detection of IMA, D-D and MCP-1 in acute myocardial infarction. Exp. Ther. Med., 2021, vol. 21, no. 5: 457. doi: 10.3892/etm.2021.9888
  6. Duan Y., Liu M., Wang J., Wei B. Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 (MCP-1) and 28-Day Mortality in Elderly Patients with Sepsis: A Retrospective Single-Center Study. Med. Sci. Monit., 2024, vol. 30: e942079. doi: 10.12659/MSM.942079
  7. Evans L., Rhodes A., Alhazzani W., Antonelli M., Coopersmith C.M., French C., Machado F.R., Mcintyre L., Ostermann M., Prescott H.C., Schorr C., Simpson S., Wiersinga W.J., Alshamsi F., Angus D.C., Arabi Y., Azevedo L., Beale R., Beilman G., Belley-Cote E., Burry L., Cecconi M., Centofanti J., Coz Yataco A., De Waele J., Dellinger R.P., Doi K., Du B., Estenssoro E., Ferrer R., Gomersall C., Hodgson C., Møller M.H., Iwashyna T., Jacob S., Kleinpell R., Klompas M., Koh Y., Kumar A., Kwizera A., Lobo S., Masur H., McGloughlin S., Mehta S., Mehta Y., Mer M., Nunnally M., Oczkowski S., Osborn T., Papathanassoglou E., Perner A., Puskarich M., Roberts J., Schweickert W., Seckel M., Sevransky J., Sprung C.L., Welte T., Zimmerman J., Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med., 2021, vol. 47, no. 11, pp. 1181–1247. doi: 10.1007/s00134-021-06506-0
  8. Gao Q., Yang L., Teng F., Guo S.B. Peripheral blood monocyte status is a predictor for judging occurrence and development on sepsis in older adult population: a case control study. BMC Emerg. Med., 2023, vol. 23, no. 1: 11. doi: 10.1186/s12873-023-00779-w
  9. Gotts J.E., Matthay M.A. Sepsis: pathophysiology and clinical management. BMJ, 2016, vol. 353: i1585. doi: 10.1136/bmj.i1585
  10. Han Y.Q., Yan L., Zhang L., Ouyang P.H., Li P., Lippi G., Hu Z.D. Performance of D-dimer for predicting sepsis mortality in the intensive care unit. Biochem. Med. (Zagreb), 2021, vol. 31, no. 2: 020709. doi: 10.11613/BM.2021.020709
  11. Iba T., Levy J.H., Levi M., Connors J.M., Thachil J. Coagulopathy of Coronavirus Disease 2019. Crit. Care Med., 2020, vol. 48, no. 9, pp. 1358–1364. doi: 10.1097/CCM.0000000000004458
  12. Iba T., Levy J.H., Warkentin T.E., Thachil J., van der Poll T., Levi M. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J. Thromb. Haemost., 2019, vol. 17, no. 11, pp. 1989–1994. doi: 10.1111/jth.14578
  13. Innocenti F., Bianchi S., Guerrini E., Vicidomini S., Conti A., Zanobetti M., Pini R. Prognostic scores for early stratification of septic patients admitted to an emergency department-high dependency unit. Eur. J. Emerg. Med., 2014, vol. 21, no. 4, pp. 254–259. doi: 10.1097/MEJ.0b013e328364e2e0
  14. Iskandar A., Prihastuti Y.A., Wulanda I.A., Aprilia A., Anshory, Muhammad. Presepsin and Mortality Risk in Sepsis: A Valuable Tool for Predicting Patient Survival. Trends Immunother., 2025, vol. 9, no. 2, pp. 107–117. doi: 10.37871/tig.id.1097
  15. Jansen M.P.B., Pulskens W.P., Butter L.M., Florquin S., Juffermans N.P., Roelofs J.J.T.H., Leemans J.C. Mitochondrial DNA is Released in Urine of SIRS Patients With Acute Kidney Injury and Correlates With Severity of Renal Dysfunction. Shock, 2018, vol. 49, no. 3, pp. 301–310. doi: 10.1097/SHK.0000000000001000
  16. Jekarl D.W., Kim J.Y., Ha J.H., Lee S., Yoo J., Kim M., Kim Y. Diagnosis and Prognosis of Sepsis Based on Use of Cytokines, Chemokines, and Growth Factors. Dis. Markers, 2019, vol. 2019: 1089107. doi: 10.1155/2019/1089107
  17. Kumar A., Roberts D., Wood K.E., Light B., Parrillo J.E., Sharma S., Suppes R., Feinstein D., Zanotti S., Taiberg L., Gurka D., Kumar A., Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit. Care Med., 2006, vol. 34, no. 6, pp. 1589–1596. doi: 10.1097/01.CCM.0000217961.75225.E9
  18. Liu V.X., Fielding-Singh V., Greene J.D., Baker J.M., Iwashyna T.J., Bhattacharya J., Escobar G.J. The Timing of Early Antibiotics and Hospital Mortality in Sepsis. Am. J. Respir. Crit. Care Med., 2017, vol. 196, no. 7, pp. 856–863. doi: 10.1164/rccm.201609-1848OC
  19. Matsumoto H., Ogura H., Shimizu K., Ikeda M., Hirose T., Matsuura H., Kang S., Takahashi K., Tanaka T., Shimazu T. The clinical importance of a cytokine network in the acute phase of sepsis. Sci. Rep., 2018, vol. 8, no. 1: 13995. doi: 10.1038/s41598-018-32291-8
  20. Mikuła T., Sapuła M., Jabłońska J., Kozłowska J., Stańczak W., Krankowska D., Wiercińska-Drapało A. Significance of Heparin-Binding Protein and D-dimers in the Early Diagnosis of Spontaneous Bacterial Peritonitis. Mediators Inflamm., 2018, vol. 2018: 1969108. doi: 10.1155/2018/1969108
  21. Rodelo J.R., De la Rosa G., Valencia M.L., Ospina S., Arango C.M., Gómez C.I., García A., Nuñez E., Jaimes F.A. D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am. J. Emerg. Med., 2012, vol. 30, no. 9, pp. 1991–1999. doi: 10.1016/j.ajem.2012.04.033
  22. Rudd K.E., Johnson S.C., Agesa K.M., Shackelford K.A., Tsoi D., Kievlan D.R., Colombara D.V., Ikuta K.S., Kissoon N., Finfer S., Fleischmann-Struzek C., Machado F.R., Reinhart K.K., Rowan K., Seymour C.W., Watson R.S., West T.E., Marinho F., Hay S.I., Lozano R., Lopez A.D., Angus D.C., Murray C.J.L., Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet, 2020, vol. 395, no. 10219, pp. 200–211. doi: 10.1016/S0140-6736(19)32989-7
  23. Schupp T., Weidner K., Rusnak J., Jawhar S., Forner J., Dulatahu F., Brück L.M., Hoffmann U., Kittel M., Bertsch T., Akin I., Behnes M. D-Dimer Levels and the Disseminated Intravascular Coagulation Score to Predict Severity and Outcomes in Sepsis or Septic Shock. Clin. Lab., 2023, vol. 69, no. 5, pp. 1229–1240. doi: 10.7754/Clin.Lab.2022.221015
  24. Schwameis M., Steiner M.M., Schoergenhofer C., Lagler H., Buchtele N., Jilma-Stohlawetz P., Boehm T., Jilma B. D-dimer and histamine in early stage bacteremia: A prospective controlled cohort study. Eur. J. Intern. Med., 2015, vol. 26, no. 10, pp. 782–786. doi: 10.1016/j.ejim.2015.10.014
  25. Semeraro F., Ammollo C.T., Caironi P., Masson S., Latini R., Panigada M., Pesenti A., Semeraro N., Gattinoni L., Colucci M. D-dimer corrected for thrombin and plasmin generation is a strong predictor of mortality in patients with sepsis. Blood Transfus., 2020, vol. 18, no. 4, pp. 304–311. doi: 10.2450/2019.0175-19
  26. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., Hotchkiss R.S., Levy M.M., Marshall J.C., Martin G.S., Opal S.M., Rubenfeld G.D., van der Poll T., Vincent J.L., Angus D.C. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, vol. 315, no. 8, pp. 801–810. doi: 10.1001/jama.2016.0287
  27. Vincent J.L., Moreno R., Takala J., Willatts S., De Mendonça A., Bruining H., Reinhart C.K., Suter P.M., Thijs L.G. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med., 1996, vol. 22, no. 7, pp. 707–710. doi: 10.1007/BF01709751
  28. Yamamoto T., Kajikawa O., Martin T.R., Sharar S.R., Harlan J.M., Winn R.K. The role of leukocyte emigration and IL-8 on the development of lipopolysaccharide-induced lung injury in rabbits. J. Immunol., 1998, vol. 161, no. 10, pp. 5704–5709. doi: 10.4049/jimmunol.161.10.5704
  29. Yunus I., Fasih A., Wang Y. The use of procalcitonin in the determination of severity of sepsis, patient outcomes and infection characteristics. PLoS One, 2018, vol. 13, no. 11: e0206527. doi: 10.1371/journal.pone.0206527
  30. Zhang L., Yan X., Fan Q., Liu H., Liu X., Liu Z., Zhang Z. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J. Thromb. Haemost., 2020, vol. 18, no. 6, pp. 1324–1329. doi: 10.1111/jth.14859
  31. Zhu T., Liao X., Feng T., Wu Q., Zhang J., Cao X., Li H. Plasma Monocyte Chemoattractant Protein 1 as a Predictive Marker for Sepsis Prognosis: A Prospective Cohort Study. Tohoku J. Exp. Med., 2017, vol. 241, no. 2, pp. 139–147. doi: 10.1620/tjem.241.139

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