Development and Validation of a Nomogram Prediction Model for Sepsis-Induced Coagulopathy: A Multicenter Retrospective Study

Abstract

Objective

This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy (SIC) in sepsis patients.

Methods

We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital (Central Campus and East Campus), and Shenxian People’s Hospital from January 2019 to September 2024. We used Kaplan-Meier analysis to assess survival outcomes. LASSO regression identified predictive variables, and logistic regression was employed to analyze risk factors for pre-SIC. A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results

Among 309 patients, 236 were in the training set, and 73 were in the test set. The pre-SIC group had higher mortality (44.8% vs. 21.3%) and disseminated intravascular coagulation (DIC) incidence (56.3% vs. 29.1%) than the non-SIC group. LASSO regression identified lactate, coagulation index, creatinine, and SIC scores as predictors of pre-SIC. The nomogram model demonstrated good calibration, with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort. DCA confirmed the model’s clinical utility.

Conclusion

SIC is associated with increased mortality, with pre-SIC further increasing the risk of death. The nomogram-based prediction model provides a reliable tool for early SIC identification, potentially improving sepsis management and outcomes.

Keywords

Sepsis / Sepsis-induced coagulopathy / Thromboelastography / Prediction model / Nomogram / Early diagnosis / Intensive care unit (ICU) / Retrospective study

References

[1] KumarS, TripathyS, JyotiA, et al.. Recent advances in biosensors for diagnosis and detection of sepsis: A comprehensive review. Biosens Bioelectron., 2019, 124–125: 205-215.

[2] SingerM, DeutschmanCS, et al.. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA., 2016, 315(8): 801-810.

[3] WilliamsB, ZouL, PittetJF, et al.. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesth Analg., 2024, 138(4): 696-711.

[4] KerriganSW, DevineT, FitzpatrickG, et al.. Early Host Interactions That Drive the Dysregulated Response in Sepsis. Front Immunol., 2019, 101748.

[5] CostantiniTW, KornblithLZ, PrittsT, et al.. The intersection of coagulation activation and inflammation after injury: What you need to know. J Trauma Acute Care Surg., 2024, 96(3): 347-356.

[6] IbaT, LevyJ, RajA, et al.. Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation. J Clin Med., 2019, 85728.

[7] CzempikPF, WiórekA. Management Strategies in Septic Coagulopathy: A Review of the Current Literature. Healthcare., 2023, 112227.

[8] IbaT, Di NisioM, ThachilJ, et al.. A Proposal of the Modification of Japanese Society on Thrombosis and Hemostasis (JSTH) Disseminated Intravascular Coagulation (DIC) Diagnostic Criteria for Sepsis-Associated DIC. Clin Appl Thromb., 2018, 24(3): 439-445.

[9] IbaT, HelmsJ, ConnorsJM, et al.. The pathophysiology, diagnosis, and management of sepsis-associated disseminated intravascular coagulation. J Intensive Care., 2023, 11124.

[10] IbaT, LevyJH, ThachilJ, et al.. Scientific and Standardization Committee on DIC of the International Society on Thrombosis and Haemostasis. The progression from coagulopathy to disseminated intravascular coagulation in representative underlying diseases. Thromb Res., 2019, 179: 11-14.

[11] IbaT, LeviM, ThachilJ, et al.. Communication from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis on sepsis-induced coagulopathy in the management of sepsis. J Thromb Haemost., 2023, 21(1): 145-153.

[12] SchmochT, MöhnleP, WeigandMA, et al.. The prevalence of sepsis-induced coagulopathy in patients with sepsis – a secondary analysis of two German multicenter randomized controlled trials. Ann Intensive Care, 2023, 1313.

[13] YamakawaK, YoshimuraJ, ItoT, et al.. External Validation of the Two Newly Proposed Criteria for Assessing Coagulopathy in Sepsis. Thromb Haemost., 2019, 119(2): 203-212.

[14] IbaT, ArakawaM, Di NisioM, et al.. Newly Proposed Sepsis-Induced Coagulopathy Precedes International Society on Thrombosis and Haemostasis Overt-Disseminated Intravascular Coagulation and Predicts High Mortality. J Intensive Care Med., 2020, 35(7): 643-649.

[15] DingR, WangZ, LinY, et al.. Comparison of a new criteria for sepsis-induced coagulopathy and International Society on Thrombosis and Haemostasis disseminated intravascular coagulation score in critically ill patients with sepsis 3.0: a retrospective study. Blood Coagul Fibrinolysis Int J Haemost Thromb., 2018, 29(6): 551-558.

[16] BurtonAG, JandreyKE. Use of Thromboelastography in Clinical Practice. Vet Clin North Am Small Anim Pract., 2020, 50(6): 1397-1409.

[17] BoscoloA, SpieziaL, De CassaiA, et al.. Are thromboelastometric and thromboelastographic parameters associated with mortality in septic patients? A systematic review and meta-analysis. J Crit Care., 2021, 61: 5-13.

[18] KimSM, KimSI, YuG. Which Septic Shock Patients With Non-Overt DIC Progress to DIC After Admission? Point-of-Care Thromboelastography Testing. Shock., 2022, 572168.

[19] DaudelF, KesslerU, FollyH, et al.. Thromboelastometry for the assessment of coagulation abnormalities in early and established adult sepsis: a prospective cohort study. Crit Care Lond Engl., 2009, 132R42.

[20] TanakaC, TagamiT, KudoS, et al.. Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: post hoc analysis of a nationwide multicenter observational study in Japan. Int J Hematol., 2021, 114(2): 164-171.

[21] IbaT, NisioMD, LevyJH, et al.. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open., 2017, 79. e017046

[22] TaylorFB, TohCH, HootsWK, et al.. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost., 2001, 86(5): 1327-1330.

[23] MüllerMC, MeijersJCM, VroomMB, et al.. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care., 2014, 18: 1-11.

[24] KimSM, KimSI, YuG, et al.. Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time. Sci Rep., 2021, 11111833.

[25] IbaT, HelmsJ, LeviM, et al.. Thromboinflammation in acute injury: infections, heatstroke, and trauma. J Thromb Haemost., 2024, 22(1): 7-22.

[26] DelabrancheX, HelmsJ, MezianiF. Immunohaemostasis: a new view on haemostasis during sepsis. Ann Intensive Care., 2017, 71117.

[27] EvansL, RhodesA, AlhazzaniW, et al.. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med., 2021, 47(11): 1181-1247.

[28] PeerapornratanaS, Manrique-CaballeroCL, GómezH, et al.. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int., 2019, 96(5): 1083-1099.

[29] KuwabaraS, GogginsE, OkusaMD. The Pathophysiology of Sepsis-Associated AKI. Clin J Am Soc Nephrol., 2022, 17(7): 1050-1069.

[30] HelmsJ, MerdjiH, LoewertS, et al.. Disseminated intravascular coagulation is strongly associated with severe acute kidney injury in patients with septic shock. Ann Intensive Care., 2023, 131119.

[31] LarsenJB, AggerbeckMA, LarsenKM, et al.. Fibrin Network Formation and Lysis in Septic Shock Patients. Int J Mol Sci., 2021, 22179540.

Funding

Natural Science Foundation of Shandong Province(ZR2024MH008)

Postdoctoral Innovation Project of Shandong Province(SDCX-ZG-202400043)

Beijing iGandan Foundation(iGandanF-1082022-RGG007)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to Huazhong University of Science and Technology