Construction of Sepsis-Related Coagulo-Inflammatory Score and it’s prognostic effects on sepsis_West China Medical Journal

Authors：

ZHOU Yaxiong , LI Dongze , YAO Rong , HE Yarong , YAO Peng ,  CAO Yu

Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

CAO Yu, Email: yuyuer@126.com

Keywords：

Sepsis; Prognosis; Inflammatory; Coagulation function; Scoring system

DOI：

10.7507/1002-0179.201810125

Video：

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Objective To build a score with the coagulation, inflammation indexes of sepsis patients, named Sepsis-Related Coagulo-Inflammatory Score (SRCIS), and then evaluate the prognostic capability of it in predicting the 28-day mortality of septic patients after the diagnosis. Methods In this prospective nested case-control study, we recruited septic patients according to the Sepsis 3.0 standards, who visited the Emergency Department, West China Hospital of Sichuan University from September 2017 to January 2018. Multiple factor analysis was conducted to confirm which coagulation or inflammation biomarkers were independent risk factors related to the 28-day mortality after their diagnosis. After that, the SRCIS was built based on those independent risk factors. Finally, receiver operating characteristic curve (ROC) analysis was conducted to verify its prognostic capability for the 28-day mortality of septic patients. Results A total of 123 cases were included. Among them, 17 patients died within 28 days, and the mortality rate was 13.8%. There were no significant differences in the demographic characteristics or comorbidities between the survival group and dead group (P>0.05). Multivariate logistic analysis showed that both activated partial thromboplastin time (APTT) [odds ratio (OR)=1.015, 95% confidence interval (CI) (1.017, 1.189), P=0.017] and C-reactive protein (CRP) [OR=1.100, 95%CI (1.006, 1.025), P=0.002] were independent risk factors for predicting the 28-day mortality of septic patients. ROC analysis indicated that the cut-off values of APTT and CRP predicting the 28-day mortality rate of sepsis were 39.25 seconds and 198.05 mg/L, respectively, and the areas under the curve (AUC) of them were 0.618 and 0.671, respectively. The results indicated that the mortality increased from 8.79% to 28.13%, when APTT prolonged to no less than 39.25 seconds (P<0.05). The mortality also increased from 8.89% to 27.27% when CRP elevated to no less than 198.05 mg/L (P<0.05). The AUC of SRCIS in predicting the 28-day mortality of patients with sepsis was 0.707, which was better than that of Sequential Organ Failure Assessment (SOFA) (AUC=0.681) and quick Sequential Organ Failure Assessment (qSOFA) (AUC=0.695). The corresponding 28-day mortality rates for patients with sepsis were 6.94%, 16.22%, and 42.86% (P<0.05), respectively, when the SRCIS score were 0, 1, and 2. Conclusions APTT and CRP are independent risk factors in predicting the 28-day mortality of patients with sepsis. Compared with traditional scoring systems such as SOFA and qSOFA, SRCIS performances better in predicting the 28-day mortality for patients with sepsis.

Citation： ZHOU Yaxiong, LI Dongze, YAO Rong, HE Yarong, YAO Peng, CAO Yu. Construction of Sepsis-Related Coagulo-Inflammatory Score and it’s prognostic effects on sepsis. West China Medical Journal, 2018, 33(11): 1388-1394. doi: 10.7507/1002-0179.201810125 Copy

1.	Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 762-774.
2.	Lagu T, Rothberg MB, Shieh MS, et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med, 2012, 40(3): 754-761.
3.	Hawiger J, Veach RA, Zienkiewicz J. New paradigms in sepsis: from prevention to protection of failing microcirculation. J Thromb Haemost, 2015, 13(10): 1743-1756.
4.	Hajj J, Blaine N, Salavaci J, et al. The " Centrality of Sepsis”: a review on incidence, mortality, and cost of care. Healthcare (Basel), 2018, 6(3): 1-11.
5.	Milano PK, Desai SA, Eiting EA, et al. Sepsis bundle adherence is associated with improved survival in severe sepsis or septic shock. West J Emerg Med, 2018, 19(5): 774-781.
6.	Levy MM, Dellinger RP, Townsend SR, et al. The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med, 2010, 38(2): 367-374.
7.	Levi M, van der Poll T. Coagulation in patients with severe sepsis. Semin Thromb Hemost, 2015, 41(1): 9-15.
8.	Simmons J, Pittet JF. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol, 2015, 28(2): 227-236.
9.	Walborn A, Hoppensteadt D, Syed D, et al. Biomarker profile of sepsis-associated coagulopathy using biochip assay for inflammatory cytokines. Clin Appl Thromb Hemost, 2018, 24(4): 625-632.
10.	Hoshino K, Kitamura T, Nakamura Y, et al. Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis. J Intensive Care, 2017, 5: 42.
11.	Su L, Feng L, Song Q, et al. Diagnostic value of dynamics serum sCD163, sTREM-1, PCT, and CRP in differentiating sepsis, severity assessment, and prognostic prediction. Mediators Inflamm, 2013: 969875.
12.	Rodelo JR, De la Rosa G, Valencia ML, et al. D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am J Emerg Med, 2012, 30(9): 1991-1999.
13.	Couto-Alves A, Wright VJ, Perumal K, et al. A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis. Crit Care, 2013, 17(2): R68.
14.	Jekarl DW, Lee SY, Lee J, et al. Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis, 2013, 75(4): 342-347.
15.	Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 801-810.
16.	谢志超, 康焰. 拯救脓毒症运动指南 2016 版指南热点解读. 华西医学, 2018, 33(7): 835-837.
17.	Stoller J, Halpin L, Weis M, et al. Epidemiology of severe sepsis: 2008-2012. J Crit Care, 2016, 31(1): 58-62.
18.	Hall MJ, Williams SN, Defrances CJ, et al. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief, 2011(62): 1-8.
19.	Weycker D, Akhras KS, Edelsberg J, et al. Long-term mortality and medical care charges in patients with severe sepsis. Crit Care Med, 2003, 31(9): 2316-2323.
20.	Li D, Zhou Y, Yu J, et al. Evaluation of a novel prognostic score based on thrombosis and inflammation in patients with sepsis: a retrospective cohort study. Clin Chem Lab Med, 2018, 56(7): 1182-1192.
21.	Goulet H, Guerand V, Bloom B, et al. Unexpected death within 72 hours of emergency department visit: were those deaths preventable. Crit Care, 2015, 19: 154.
22.	Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med, 2017, 45(3): 486-552.
23.	Kalil AC, Florescu DF. Severe sepsis: are PROWESS and PROWESS-SHOCK trials comparable? A clinical and statistical heterogeneity analysis. Crit Care, 2013, 17(4): 167.
24.	Barbash IJ. Immunosuppression and heterogeneity in the sepsis volume-outcome relationship. Ann Am Thorac Soc, 2018, 15(8): 916-918.
25.	Sadaka F, Ethmaneabouelmaali C, Cytron MA, et al. Predicting mortality of patients with sepsis: a comparison of APACHE Ⅱ and APACHE Ⅲ scoring systems. J Clin Med Res, 2017, 9(11): 907-910.
26.	Khwannimit B, Bhurayanontachai R, Vattanavanit V. Comparison of the performance of SOFA, qSOFA and SIRS for predicting mortality and organ failure among sepsis patients admitted to the intensive care unit in a middle-income country. J Crit Care, 2018, 44: 156-160.
27.	魏薇, 夏义琴, 曹钰. 快速序贯器官衰竭评分对脓毒症休克早期预测能力评价. 华西医学, 2017, 32(6): 812-818.
28.	Lipinska-Gediga M. Coagulopathy in sepsis: a new look at an old problem. Anaesthesiol Intensive Ther, 2016, 48(5): 352-359.
29.	Levi M. The coagulant response in sepsis. Clin Chest Med, 2008, 29(4): 627.
30.	van Vught LA, Wiewel MA, Hoogendijk AJ, et al. The host response in patients with sepsis developing intensive care unit-acquired secondary infections. Am J Respir Crit Care Med, 2017, 196(4): 458-470.
31.	Ishikura H, Nakamura Y, Kawano Y, et al. Intravenous immunoglobulin improves sepsis-induced coagulopathy: a retrospective, single-center observational study. J Crit Care, 2015, 30(3): 579-583.
32.	Kaneider NC, Förster E, Mosheimer B, et al. Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial adherence of neutrophils by antithrombin. Thromb Haemost, 2003, 90(6): 1150-1157.
33.	Esmon CT. New mechanisms for vascular control of inflammation mediated by natural anticoagulant proteins. J Exp Med, 2002, 196(5): 561-564.
34.	Gradel KO, Jensen TG, Kolmos HJ, et al. Does C-reactive protein independently predict mortality in adult community-acquired bacteremia patients with known sepsis severity?. APMIS, 2013, 121(9): 835-842.
35.	Yamamoto S, Yamazaki S, Shimizu T, et al. Prognostic utility of serum CRP levels in combination with CURB-65 in patients with clinically suspected sepsis: a decision curve analysis. BMJ Open, 2015, 5(4): e007049.
36.	Liu D, Su LX, Han GC, et al. Prognostic value of procalcitonin in adult patients with sepsis: a systematic review and Meta-analysis. PLoS One, 2015, 10(6): e0129450.
37.	Benediktsson S, Frigyesi A, Kander T. Routine coagulation tests on ICU admission are associated with mortality in sepsis: an observational study. Acta Anaesthesiol Scand, 2017, 61(7): 790-796.
38.	Mihajlovic D, Lendak D, Mitic G, et al. Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis. Turk J Med Sci, 2015, 45(1): 93-98.

1. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 762-774.
2. Lagu T, Rothberg MB, Shieh MS, et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med, 2012, 40(3): 754-761.
3. Hawiger J, Veach RA, Zienkiewicz J. New paradigms in sepsis: from prevention to protection of failing microcirculation. J Thromb Haemost, 2015, 13(10): 1743-1756.
4. Hajj J, Blaine N, Salavaci J, et al. The " Centrality of Sepsis”: a review on incidence, mortality, and cost of care. Healthcare (Basel), 2018, 6(3): 1-11.
5. Milano PK, Desai SA, Eiting EA, et al. Sepsis bundle adherence is associated with improved survival in severe sepsis or septic shock. West J Emerg Med, 2018, 19(5): 774-781.
6. Levy MM, Dellinger RP, Townsend SR, et al. The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med, 2010, 38(2): 367-374.
7. Levi M, van der Poll T. Coagulation in patients with severe sepsis. Semin Thromb Hemost, 2015, 41(1): 9-15.
8. Simmons J, Pittet JF. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol, 2015, 28(2): 227-236.
9. Walborn A, Hoppensteadt D, Syed D, et al. Biomarker profile of sepsis-associated coagulopathy using biochip assay for inflammatory cytokines. Clin Appl Thromb Hemost, 2018, 24(4): 625-632.
10. Hoshino K, Kitamura T, Nakamura Y, et al. Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis. J Intensive Care, 2017, 5: 42.
11. Su L, Feng L, Song Q, et al. Diagnostic value of dynamics serum sCD163, sTREM-1, PCT, and CRP in differentiating sepsis, severity assessment, and prognostic prediction. Mediators Inflamm, 2013: 969875.
12. Rodelo JR, De la Rosa G, Valencia ML, et al. D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. Am J Emerg Med, 2012, 30(9): 1991-1999.
13. Couto-Alves A, Wright VJ, Perumal K, et al. A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis. Crit Care, 2013, 17(2): R68.
14. Jekarl DW, Lee SY, Lee J, et al. Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis, 2013, 75(4): 342-347.
15. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA, 2016, 315(8): 801-810.
16. 谢志超, 康焰. 拯救脓毒症运动指南 2016 版指南热点解读. 华西医学, 2018, 33(7): 835-837.
17. Stoller J, Halpin L, Weis M, et al. Epidemiology of severe sepsis: 2008-2012. J Crit Care, 2016, 31(1): 58-62.
18. Hall MJ, Williams SN, Defrances CJ, et al. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief, 2011(62): 1-8.
19. Weycker D, Akhras KS, Edelsberg J, et al. Long-term mortality and medical care charges in patients with severe sepsis. Crit Care Med, 2003, 31(9): 2316-2323.
20. Li D, Zhou Y, Yu J, et al. Evaluation of a novel prognostic score based on thrombosis and inflammation in patients with sepsis: a retrospective cohort study. Clin Chem Lab Med, 2018, 56(7): 1182-1192.
21. Goulet H, Guerand V, Bloom B, et al. Unexpected death within 72 hours of emergency department visit: were those deaths preventable. Crit Care, 2015, 19: 154.
22. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med, 2017, 45(3): 486-552.
23. Kalil AC, Florescu DF. Severe sepsis: are PROWESS and PROWESS-SHOCK trials comparable? A clinical and statistical heterogeneity analysis. Crit Care, 2013, 17(4): 167.
24. Barbash IJ. Immunosuppression and heterogeneity in the sepsis volume-outcome relationship. Ann Am Thorac Soc, 2018, 15(8): 916-918.
25. Sadaka F, Ethmaneabouelmaali C, Cytron MA, et al. Predicting mortality of patients with sepsis: a comparison of APACHE Ⅱ and APACHE Ⅲ scoring systems. J Clin Med Res, 2017, 9(11): 907-910.
26. Khwannimit B, Bhurayanontachai R, Vattanavanit V. Comparison of the performance of SOFA, qSOFA and SIRS for predicting mortality and organ failure among sepsis patients admitted to the intensive care unit in a middle-income country. J Crit Care, 2018, 44: 156-160.
27. 魏薇, 夏义琴, 曹钰. 快速序贯器官衰竭评分对脓毒症休克早期预测能力评价. 华西医学, 2017, 32(6): 812-818.
28. Lipinska-Gediga M. Coagulopathy in sepsis: a new look at an old problem. Anaesthesiol Intensive Ther, 2016, 48(5): 352-359.
29. Levi M. The coagulant response in sepsis. Clin Chest Med, 2008, 29(4): 627.
30. van Vught LA, Wiewel MA, Hoogendijk AJ, et al. The host response in patients with sepsis developing intensive care unit-acquired secondary infections. Am J Respir Crit Care Med, 2017, 196(4): 458-470.
31. Ishikura H, Nakamura Y, Kawano Y, et al. Intravenous immunoglobulin improves sepsis-induced coagulopathy: a retrospective, single-center observational study. J Crit Care, 2015, 30(3): 579-583.
32. Kaneider NC, Förster E, Mosheimer B, et al. Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial adherence of neutrophils by antithrombin. Thromb Haemost, 2003, 90(6): 1150-1157.
33. Esmon CT. New mechanisms for vascular control of inflammation mediated by natural anticoagulant proteins. J Exp Med, 2002, 196(5): 561-564.
34. Gradel KO, Jensen TG, Kolmos HJ, et al. Does C-reactive protein independently predict mortality in adult community-acquired bacteremia patients with known sepsis severity?. APMIS, 2013, 121(9): 835-842.
35. Yamamoto S, Yamazaki S, Shimizu T, et al. Prognostic utility of serum CRP levels in combination with CURB-65 in patients with clinically suspected sepsis: a decision curve analysis. BMJ Open, 2015, 5(4): e007049.
36. Liu D, Su LX, Han GC, et al. Prognostic value of procalcitonin in adult patients with sepsis: a systematic review and Meta-analysis. PLoS One, 2015, 10(6): e0129450.
37. Benediktsson S, Frigyesi A, Kander T. Routine coagulation tests on ICU admission are associated with mortality in sepsis: an observational study. Acta Anaesthesiol Scand, 2017, 61(7): 790-796.
38. Mihajlovic D, Lendak D, Mitic G, et al. Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis. Turk J Med Sci, 2015, 45(1): 93-98.

West China Medical Journal

Construction of Sepsis-Related Coagulo-Inflammatory Score and it’s prognostic effects on sepsis

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