Hemostatic Alterations and Sepsis-Induced Coagulopathy: Epidemiology, Complications, and Mortality Risk Factors
Keywords:
Sepsis, Coagulopathy, DIC, Thrombosis, Mortality
Abstract
Abstract Background: Sepsis is associated with significant alterations in coagulation, often leading to disseminated intravascular coagulation (DIC) and increased mortality. This study aimed to evaluate hemostatic changes, the occurrence of DIC, hemorrhagic and thrombo-ischemic complications, and factors influencing mortality in septic patients.
Methods: A prospective observational study was conducted on septic patients admitted to the intensive care unit. Hemostatic parameters including platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimers were measured. DIC was assessed using ISTH, JAAM, and SIC scores. Complications and mortality were recorded, and statistical analyses were performed to identify associated risk factors.
Results: Hemostatic alterations were observed in nearly 95% of patients. Thrombocytopenia (<150,000/µL) was present in 37%, with a mean platelet count of 195,232 ± 114,298/µL. PT and aPTT were abnormal in 34% and 27% of cases, respectively. D-dimers were elevated in 95% of patients, while fibrinogen was high in 76% of cases. DIC occurred in 21% of patients by ISTH, 35% by JAAM, and 45% by SIC criteria. Hemorrhagic complications were observed in 8.5% of patients, and thrombo-ischemic events in 13%. Higher ISTH, JAAM, and SIC scores at admission were significantly associated with increased mortality, with odds ratios of 1.62, 1.47, and 1.43, respectively.
Conclusion: Hemostatic disturbances are common in sepsis, with a significant proportion developing DIC. Complications, both hemorrhagic and thrombo-ischemic, contribute to mortality. Early recognition using scoring systems such as ISTH, JAAM, and SIC can help identify high-risk patients and guide management strategies.
Keywords: Sepsis, Coagulopathy, DIC, Hemorrhage, Thrombosis, Mortality
References
References
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28. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 17 oct 2001;286(15):1869‑78.
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31. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 8 mars 2001;344(10):699‑709.
32. Bernard GR, Margolis BD, Shanies HM, Ely EW, Wheeler AP, Levy H, et al. Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest. juin 2004;125(6):2206‑16.
33. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study - PubMed [Internet]. [cité 6 juin 2024]. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/11112234/
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35. Mouhat B, Besutti M, Bouiller K, Grillet F, Monnin C, Ecarnot F, et al. Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients. European Respiratory Journal [Internet]. 1 oct 2020 [cité 18 juin 2024];56(4). Disponible sur: https://erj.ersjournals.com/content/56/4/2001811
36. Kollias A, Kyriakoulis KG, Lagou S, Kontopantelis E, Stergiou GS, Syrigos K. Venous thromboembolism in COVID-19: A systematic review and meta-analysis. Vasc Med. août 2021;26(4):415‑25.
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1. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, Wilmer A, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med. juin 2000;28(6):1871‑6.
2. Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn EG. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit Care Med. août 2002;30(8):1765‑71.
3. Bloos F, Trips E, Nierhaus A, Briegel J, Heyland DK, Jaschinski U, et al. Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial. JAMA Internal Medicine. 1 sept 2016;176(9):1266‑76.
4. Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, et al. Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Critical Care. 10 févr 2004;8(2):R82.
5. Ding R, Wang Z, Lin Y, Liu B, Zhang Z, Ma X. 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. sept 2018;29(6):551‑8.
6. Epidemiology of disseminated intravascular coagulation in sepsis and validation of scoring systems - ScienceDirect [Internet]. [cité 12 mai 2024]. Disponible sur: https://www.sciencedirect.com/science/article/abs/pii/S0883944118306798?via%3Dihub
7. Akca S, Haji-Michael P, de Mendonça A, Suter P, Levi M, Vincent JL. Time course of platelet counts in critically ill patients. Crit Care Med. avr 2002;30(4):753‑6.
8. François B, Trimoreau F, Vignon P, Fixe P, Praloran V, Gastinne H. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med. août 1997;103(2):114‑20.
9. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome - PubMed [Internet]. [cité 7 juin 2024]. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/14633796/
10. Melansi S, Rahmawati E, Susilawati S. Correlation between Hemostasis Profile and Sepsis Outcome. Indonesian J Clin Pathol Med Lab. 7 déc 2020;27(1):60‑5.
11. Mesters RM, Mannucci PM, Coppola R, Keller T, Ostermann H, Kienast J. Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. Blood. 1 août 1996;88(3):881‑6.
12. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications - PubMed [Internet]. [cité 6 juin 2024]. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/10921542/
13. Taylor F, Toh CH, Hoots K, Wada H, Levi M. Towards Definition, Clinical and Laboratory Criteria, and a Scoring System for Disseminated Intravascular Coagulation: On behalf of the Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb Haemost. 2001;86(11):1327‑30.
14. Shorr AF, Thomas SJ, Alkins SA, Fitzpatrick TM, Ling GS. D-dimer correlates with proinflammatory cytokine levels and outcomes in critically ill patients. Chest. avr 2002;121(4):1262‑8.
15. Levi M, Meijers JC. DIC: Which laboratory tests are most useful. Blood Reviews. 1 janv 2011;25(1):33‑7.
16. Bakhtiari K, Meijers JCM, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation*. Critical Care Medicine. déc 2004;32(12):2416.
17. The thromboelastometric discrepancy between septic and trauma induced disseminated intravascular coagulation diagnosed by the scoring system from the Japanese association for acute medicine - PubMed [Internet]. [cité 6 juin 2024]. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/27495106/
18. Angstwurm MWA, Dempfle CE, Spannagl M. New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores. Crit Care Med. févr 2006;34(2):314‑20; quiz 328.
19. Dhainaut JF, Yan SB, Joyce DE, Pettilä V, Basson B, Brandt JT, et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. nov 2004;2(11):1924‑33.
20. Ogura H, Gando S, Saitoh D, Takeyama N, Kushimoto S, Fujishima S, et al. Epidemiology of severe sepsis in Japanese intensive care units: a prospective multicenter study. J Infect Chemother. mars 2014;20(3):157‑62.
21. S G, T I, Y E, Y O, K O, K K, et al. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Critical care medicine [Internet]. mars 2006 [cité 3 nov 2023];34(3). Disponible sur: https://pubmed.ncbi.nlm.nih.gov/16521260/
22. Singh RK, Baronia AK, Sahoo JN, Sharma S, Naval R, Pandey CM, et al. Prospective comparison of new Japanese Association for Acute Medicine (JAAM) DIC and International Society of Thrombosis and Hemostasis (ISTH) DIC score in critically ill septic patients. Thromb Res. avr 2012;129(4):e119-125.
23. Takemitsu T, Wada H, Hatada T, Ohmori Y, Ishikura K, Takeda T, et al. Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation. Thromb Haemost. 2011;105(1):40‑4.
24. Schmoch T, Möhnle P, Weigand MA, Briegel J, Bauer M, Bloos F, 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. 12 janv 2023;13(1):3.
25. Keh D, Trips E, Marx G, Wirtz SP, Abduljawwad E, Bercker S, et al. Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA. 1 nov 2016;316(17):1775‑85.
26. Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 1 sept 2017;7(9):e017046.
27. Mimuro J, Takahashi H, Kitajima I, Tsuji H, Eguchi Y, Matsushita T, et al. Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation. Thromb Res. mai 2013;131(5):436‑43.
28. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 17 oct 2001;286(15):1869‑78.
29. Antithrombin concentrate use in disseminated intravascular coagulation of sepsis: meta-analyses revisited - PubMed [Internet]. [cité 7 juin 2024]. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/29316235/
30. Taylor FB, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. nov 2001;86(5):1327‑30.
31. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 8 mars 2001;344(10):699‑709.
32. Bernard GR, Margolis BD, Shanies HM, Ely EW, Wheeler AP, Levy H, et al. Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest. juin 2004;125(6):2206‑16.
33. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study - PubMed [Internet]. [cité 6 juin 2024]. Disponible sur: https://pubmed.ncbi.nlm.nih.gov/11112234/
34. Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, et al. Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels. Radiology. sept 2020;296(3):E189‑91.
35. Mouhat B, Besutti M, Bouiller K, Grillet F, Monnin C, Ecarnot F, et al. Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients. European Respiratory Journal [Internet]. 1 oct 2020 [cité 18 juin 2024];56(4). Disponible sur: https://erj.ersjournals.com/content/56/4/2001811
36. Kollias A, Kyriakoulis KG, Lagou S, Kontopantelis E, Stergiou GS, Syrigos K. Venous thromboembolism in COVID-19: A systematic review and meta-analysis. Vasc Med. août 2021;26(4):415‑25.
37. Semeraro N, Ammollo CT, Semeraro F, Colucci M. Sepsis-associated disseminated intravascular coagulation and thromboembolic disease. Mediterr J Hematol Infect Dis. 13 août 2010;2(3):e2010024.
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