Thromb Haemost 2024; 124(05): 399-407
DOI: 10.1055/a-2196-3630
Coagulation and Fibrinolysis

Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis

Tadashi Matsuoka
1   Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan
,
2   Department of Emergency and Critical Care Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
,
3   Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
,
Koichiro Homma
1   Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan
,
Junichi Sasaki
1   Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan
› Author Affiliations
Funding This work was supported by JSTH research grant program for DIC with acute illness (Grant #2023–001) and JSPS KAKENHI (Grant #22K16630).


Abstract

Background Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy.

Objectives To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients.

Methods This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup “high risk of death in DIC” and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (−/−), early-recovered DIC (+/−), late-onset DIC (−/+), and persistent DIC (+/+).

Results A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, “high-risk” DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors.

Conclusion This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.

Supplementary Material



Publication History

Received: 12 July 2023

Accepted: 21 October 2023

Accepted Manuscript online:
23 October 2023

Article published online:
21 November 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369 (09) 840-851
  • 2 Levi M, Schultz M, van der Poll T. Sepsis and thrombosis. Semin Thromb Hemost 2013; 39 (05) 559-566
  • 3 Esmon CT. The interactions between inflammation and coagulation. Br J Haematol 2005; 131 (04) 417-430
  • 4 Ogura H, Gando S, Saitoh D. et al; Japanese Association for Acute Medicine Sepsis Registry (JAAMSR) Study Group. Epidemiology of severe sepsis in Japanese intensive care units: a prospective multicenter study. J Infect Chemother 2014; 20 (03) 157-162
  • 5 Gando S. Role of fibrinolysis in sepsis. Semin Thromb Hemost 2013; 39 (04) 392-399
  • 6 Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood 2019; 133 (09) 906-918
  • 7 Chang JC. Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease. Thromb J 2019; 17: 10
  • 8 Yamakawa K, Umemura Y, Hayakawa M. et al; Japan Septic Disseminated Intravascular Coagulation (J-Septic DIC) study group. Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan. Crit Care 2016; 20 (01) 229
  • 9 Yamakawa K, Yoshimura J, Ito T, Hayakawa M, Hamasaki T, Fujimi S. External validation of the two newly proposed criteria for assessing coagulopathy in sepsis. Thromb Haemost 2019; 119 (02) 203-212
  • 10 Gando S, Shiraishi A, Yamakawa K. et al; Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) Study Group. Role of disseminated intravascular coagulation in severe sepsis. Thromb Res 2019; 178: 182-188
  • 11 Vincent JL, Francois B, Zabolotskikh I. et al; SCARLET Trial Group. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the SCARLET randomized clinical trial. JAMA 2019; 321 (20) 1993-2002
  • 12 François B, Fiancette M, Helms J. et al. Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET. Ann Intensive Care 2021; 11 (01) 53
  • 13 Yamakawa K, Levy JH, Iba T. Recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy (SCARLET): an updated meta-analysis. Crit Care 2019; 23 (01) 302
  • 14 Hayakawa M, Yamakawa K, Saito S. et al; Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study group. Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation. A multicentre retrospective study. Thromb Haemost 2016; 115 (06) 1157-1166
  • 15 Hayakawa M, Yamakawa K, Saito S. et al. Nationwide registry of sepsis patients in Japan focused on disseminated intravascular coagulation 2011-2013. Sci Data 2018; 5: 180243
  • 16 Levy MM, Fink MP, Marshall JC. et al; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31 (04) 1250-1256
  • 17 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315 (08) 801-810
  • 18 Taylor Jr 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 2001; 86 (05) 1327-1330
  • 19 Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers 2016; 2: 16037
  • 20 Gando S, Otomo Y. Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. Crit Care 2015; 19 (01) 72
  • 21 Iba T, Umemura Y, Watanabe E, Wada T, Hayashida K, Kushimoto S. Japanese Surviving Sepsis Campaign Guideline Working Group for disseminated intravascular coagulation. Diagnosis of sepsis-induced disseminated intravascular coagulation and coagulopathy. Acute Med Surg 2019; 6 (03) 223-232
  • 22 Yamakawa K, Umemura Y, Murao S, Hayakawa M, Fujimi S. Optimal timing and early intervention with anticoagulant therapy for sepsis-induced disseminated intravascular coagulation. Clin Appl Thromb Hemost 2019; 25: 1076029619835055
  • 23 Umemura Y, Yamakawa K, Ogura H, Yuhara H, Fujimi S. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials. J Thromb Haemost 2016; 14 (03) 518-530
  • 24 Freeman BD, Zehnbauer BA, Buchman TG. A meta-analysis of controlled trials of anticoagulant therapies in patients with sepsis. Shock 2003; 20 (01) 5-9