Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities: A Retrospective Cohort Study

Abstract

Objective

Coagulation abnormalities are common and prognostically significant in intensive care units (ICUs) and are associated with increased mortality. This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities.

Methods

This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022. The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0. Patients were followed up for 28 days, and multivariate logistic regression analysis was utilized to identify risk factors for mortality.

Results

Of the 451 patients analyzed, 115 died, and 336 were alive at the end of the 28-day period. Multivariate analysis revealed that elevated thrombin-antithrombin complex (TAT), tissue plasminogen activator inhibitor complex (tPAIC), prolonged prothrombin time, and thrombocytopenia were independent risk factors for mortality. For nonovert disseminated intravascular coagulation (DIC) patients, older age and thrombocytopenia were associated with increased risks of mortality, whereas elevated levels of plasmin α₂-plasmin inhibitor complex (PIC) were found to be independent predictors of survival. In patients with overt DIC, elevated levels of tPAIC were independently associated with increased risks of mortality. Nevertheless, thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC.

Conclusion

Coagulation markers such as the TAT, tPAIC, PIC, and platelet count were significantly associated with mortality, underscoring the importance of maintaining a balance between coagulation and fibrinolysis. These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

References

[1] Levi M, Opal SM. Coagulation abnormalities in critically ill patients. Crit Care, 2006, 10(4): 222

[2] Helms J, Iba T, Connors JM, et al.. How to manage coagulopathies in critically ill patients. Intensive Care Med, 2023, 49(3): 273-290

[3] Morrison JL, Cai Q, Davis N, et al.. Clinical and economic outcomes of the electronic intensive care unit: results from two community hospitals. Crit Care Med, 2010, 38(1): 2-8

[4] Hjorleifsson E, Sigurdsson MI, Gudmundsdottir BR, et al.. Prediction of survival in patients suspected of disseminated intravascular coagulation. Acta Anesthesiol Scand, 2015, 59(7): 870-880

[5] Lorente JA, García-Frade LJ, Landín L, et al.. Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest, 1993, 103(5): 1536-1542

[6] Kelly BJ, Lautenbach E, Nachamkin I, et al.. Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis. Crit Care Med, 2018, 46(7): 1106-1113

[7] Stensballe J, Henriksen HH, Johansson PI. Early hemorrhage control and management of trauma-induced coagulopathy: the importance of goal-directed therapy. Curr Opin Crit Care, 2017, 23(6): 503-510

[8] Liu Y, Gao W, Guo W, et al.. Prominent coagulation disorder is closely related to inflammatory response and could be as a prognostic indicator for ICU patients with COVID-19. J Thromb Thrombolysis, 2020, 50(4): 825-832

[9] Azuhata T, Hayakwa M, Maekawa K, et al.. Supernormal Antithrombin Activity Is an Independent Predictor of In-Hospital Mortality in Patients With Sepsis: A Retrospective Observational Study. Clin Appl Thromb Hemost, 2020, 26: 1076029620912827

[10] Matsubara T, Yamakawa K, Umemura Y, et al.. Significance of plasma fibrinogen level and antithrombin activity in sepsis: A multicenter cohort study using a cubic spline model. Thromb Res, 2019, 181: 17-23

[11] Claushuis TA, van Vught LA, Scicluna BP, et al.. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood, 2016, 127(24): 3062-3072

[12] Bai H, Shen L, Zhang H, et al.. Clinical value of TAT, PIC and t-PAIC as predictive markers for severe sepsis in pediatric patients. Front Pediatr, 2024, 12: 1336583

[13] Mei H, Jiang Y, Luo L, et al.. Evaluation the combined diagnostic value of TAT, PIC, tPAIC, and sTM in disseminated intravascular coagulation: A multicenter prospective observational study. Thromb Res, 2019, 173: 20-26

[14] Zhou K, Zhang J, Zheng ZR, et al.. Diagnostic and Prognostic Value of TAT, PIC, TM, and t-PAIC in Malignant Tumor Patients with Venous Thrombosis. Clin Appl Thromb Hemost, 2020, 26: 1076029620971041

[15] Yan SQ, Guo T. Diagnosis and related molecular markers of disseminated intravascular coagulation. J Clin Hematol (Chinese), 2019, 32(1): 13-15

[16] Popescu NI, Lupu C, Lupu F. Disseminated intravascular coagulation and its immune mechanisms. Blood, 2022, 139(13): 1973-1986

[17] Taylor FB Jr Toh CH, Hoots WK, et al.. Toward definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Hemost, 2001, 86(5): 1327-1330

[18] Chiu C, Legrand M. Epidemiology of sepsis and septic shock. Curr Opin Anesthesiol, 2021, 34(2): 71-76

[19] Dhainaut JF, Shorr AF, Macias WL, et al.. Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure. Crit Care Med, 2005, 33(2): 341-348

[20] Gando S, Saitoh D, Ogura H, et al.. Natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey. Crit Care Med, 2008, 36(1): 145-150

[21] Ten Cate H. Trombocytopenia: one of the markers of disseminated intravascular coagulation. Pathophysiol Hemost Thromb, 2003, 33(5–6): 413-416

[22] Wada H, Hatada T, Okamoto K, et al.. Modified nonovert DIC diagnostic criteria predict the early phase of overt-DIC. Am J Hematol, 2010, 85(9): 691-694

[23] Wada H, Wakita Y, Nakase T, et al.. Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun. Mie DIC Study Group. Thromb Hemost, 1995, 74(3): 848-852

[24] Okamoto K, Wada H, Hatada T, et al.. Frequency and hemostatic abnormalities in pre-DIC patients. Thromb Res, 2010, 126(1): 74-78

[25] Gando S, Kameue T, Nanzaki S, et al.. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Hemost, 1996, 75(2): 224-228

[26] Umemura Y, Yamakawa K. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials: reply. J Thromb Hemost, 2016, 14(11): 2310-2311

[27] Yamakawa K, Umemura Y, Hayakawa M, et al.. Benefit profile of anticoagulant therapy in sepsis: a nationwide multicenter registry in Japan. Crit Care, 2016, 20(1): 229

[28] Yatabe T, Inoue S, Sakamoto S, et al.. The anticoagulant treatment for sepsis induced disseminated intravascular coagulation; network meta-analysis. Thromb Res, 2018, 171: 136-142

[29] Zarychanski R, Abou-Setta AM, Kanji S, et al.. The efficacy and safety of heparin in patients with sepsis: a systematic review and metaanalysis. Crit Care Med, 2015, 43(3): 511-518

[30] Wang L, Chai Y. Chinese emergency medicine expert consensus on diagnosis and treatment of sepsis complicated with disseminated intravascular coagulation. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2017, 29(7): 577-580 (Chinese)

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Huazhong University of Science and Technology