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Thromb Haemost 2019; 119(02): 203-212
DOI: 10.1055/s-0038-1676610
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

External Validation of the Two Newly Proposed Criteria for Assessing Coagulopathy in Sepsis

Kazuma Yamakawa
1   Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
,
Jumpei Yoshimura
1   Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
,
Takashi Ito
2   Department of Emergency and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
,
Mineji Hayakawa
3   Emergency and Critical Care Center, Hokkaido University Hospital, Sapporo, Japan
,
Toshimitsu Hamasaki
4   Department of Biostatistics and Data Management, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Satoshi Fujimi
1   Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
› Author Affiliations
Further Information

Publication History

11 August 2018

01 November 2018

Publication Date:
28 December 2018 (online)

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Abstract

Background Two different criteria for evaluating coagulopathy in sepsis were recently released: sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC). Although both use universal haemostatic markers of platelet count and pro-thrombin time, significance and usefulness of these criteria remain unclear.

Objective This article validates and evaluates the significance of SIC and SAC criteria compared with the International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) and Japanese Association for Acute Medicine (JAAM) DIC criteria.

Methods Clinical characteristics of patients from a nationwide Japanese cohort were classified by SIC, SAC or DIC status and relations between criteria were examined. We evaluated associations between in-hospital mortality and anticoagulant therapy according to the SIC, SAC or DIC status to clarify the significance of criteria for introducing anticoagulants. Intervention effects were analysed by Cox regression analysis adjusted by propensity scoring.

Results Incidences of coagulopathy diagnosed by SIC and JAAM DIC were similar, whereas those of SAC and ISTH overt DIC were about half of the former two (61.4%, 60.8% vs. 45.3%, 29.3%). Severity and mortality of all criteria were almost comparable. For validating initiation of anticoagulation, favourable effects of anticoagulant therapy were observed only in sub-sets with, and not without, coagulopathy diagnosed by all four criteria. Slight non-significant differences between anticoagulant groupings were found in ISTH overt DIC- and SAC-negative populations, suggesting that some patients even ‘without’ these criteria may benefit from anticoagulant therapy.

Conclusion Newly developed SIC diagnostic criteria for coagulopathy may be valuable in detecting appropriate candidates for anticoagulant therapy in sepsis and a useful alternative to conventional DIC scoring systems.

Keywords

anticoagulants - coagulopathy - critically ill - disseminated intravascular coagulation - septic shock

Supplementary Material

 

  • References

  • 1 Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med 2015; 372 (09) 793-795
    CrossrefPubMedGoogle Scholar
  • 2 Jameson JL, Longo DL. Precision medicine--personalized, problematic, and promising. N Engl J Med 2015; 372 (23) 2229-2234
    CrossrefPubMedGoogle Scholar
  • 3 Vincent JL. The coming era of precision medicine for intensive care. Crit Care 2017; 21 (Suppl. 03) 314
    CrossrefPubMedGoogle Scholar
  • 4 Seymour CW, Gomez H, Chang CH. , et al. Precision medicine for all? Challenges and opportunities for a precision medicine approach to critical illness. Crit Care 2017; 21 (01) 257
    CrossrefPubMedGoogle Scholar
  • 5 Ranieri VM, Thompson BT, Barie PS. , et al; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012; 366 (22) 2055-2064
    CrossrefPubMedGoogle Scholar
  • 6 Warren BL, Eid A, Singer P. , et al; KyberSept Trial Study Group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001; 286 (15) 1869-1878
    CrossrefPubMedGoogle Scholar
  • 7 Abraham E, Reinhart K, Opal S. , et al; OPTIMIST Trial Study Group. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003; 290 (02) 238-247
    CrossrefPubMedGoogle Scholar
  • 8 Dhainaut JF, Yan SB, Joyce DE. , et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost 2004; 2 (11) 1924-1933
    CrossrefPubMedGoogle Scholar
  • 9 Kienast J, Juers M, Wiedermann CJ. , et al; KyberSept investigators. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation. J Thromb Haemost 2006; 4 (01) 90-97
    PubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 Kudo D, Hayakawa M, Ono K, Yamakawa K. Impact of non-anticoagulant therapy on patients with sepsis-induced disseminated intravascular coagulation: a multicenter, case-control study. Thromb Res 2018; 163: 22-29
    CrossrefPubMedGoogle Scholar
  • 13 Nishida O, Ogura H, Egi M. , et al. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016). Acute Med Surg 2018; 5 (01) 3-89
    CrossrefPubMedGoogle Scholar
  • 14 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 (03) 486-552
    CrossrefPubMedGoogle Scholar
  • 15 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Gando S, Iba T, Eguchi Y. , et al; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med 2006; 34 (03) 625-631
    CrossrefPubMedGoogle Scholar
  • 17 Gando S, Wada H, Asakura H. , et al. Evaluation of new Japanese diagnostic criteria for disseminated intravascular coagulation in critically ill patients. Clin Appl Thromb Hemost 2005; 11 (01) 71-76
    CrossrefPubMedGoogle Scholar
  • 18 Di Nisio M, Thachil J, Squizzato A. Management of disseminated intravascular coagulation: a survey of the International Society on Thrombosis and Haemostasis. Thromb Res 2015; 136 (02) 239-242
    CrossrefPubMedGoogle Scholar
  • 19 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 2017; 7 (09) e017046
    CrossrefPubMedGoogle Scholar
  • 20 Lyons PG, Micek ST, Hampton N, Kollef MH. Sepsis-associated coagulopathy severity predicts hospital mortality. Crit Care Med 2018; 46 (05) 736-742
    CrossrefPubMedGoogle Scholar
  • 21 Hayakawa M, Saito S, Uchino S. , et al. Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013. J Intensive Care 2016; 4: 44
    CrossrefPubMedGoogle Scholar
  • 22 Bone RC, Balk RA, Cerra FB. , et al; The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992; 101 (06) 1644-1655
    CrossrefPubMedGoogle Scholar
  • 23 Vincent JL, Moreno R, Takala J. , et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22 (07) 707-710
    CrossrefPubMedGoogle Scholar
  • 24 Gando S, Saitoh D, Ogura H. , et al; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. Disseminated intravascular coagulation (DIC) diagnosed based on the Japanese Association for Acute Medicine criteria is a dependent continuum to overt DIC in patients with sepsis. Thromb Res 2009; 123 (05) 715-718
    CrossrefPubMedGoogle Scholar
  • 25 Umemura Y, Yamakawa K. Optimal patient selection for anticoagulant therapy in sepsis: an evidence-based proposal from Japan. J Thromb Haemost 2018; 16 (03) 462-464
    CrossrefPubMedGoogle Scholar
  • 26 Umemura Y, Yamakawa K, Hayakawa M, Hamasaki T, Fujimi S. ; Japan Septic Disseminated Intravascular Coagulation (J-Septic DIC) study group. Screening itself for disseminated intravascular coagulation may reduce mortality in sepsis: a nationwide multicenter registry in Japan. Thromb Res 2018; 161: 60-66
    CrossrefPubMedGoogle Scholar
  • 27 Vincent JL, Ramesh MK, Ernest D. , et al. A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation. Crit Care Med 2013; 41 (09) 2069-2079
    CrossrefPubMedGoogle Scholar
  • 28 Perner A, Rhodes A, Venkatesh B. , et al. Sepsis: frontiers in supportive care, organisation and research. Intensive Care Med 2017; 43 (04) 496-508
    CrossrefPubMedGoogle Scholar
  • 29 Iba T, Gando S, Thachil J. Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation: the view from Japan. J Thromb Haemost 2014; 12 (07) 1010-1019
    CrossrefPubMedGoogle Scholar
  • 30 Iba T, Arakawa M, Levy JH. , et al. Sepsis-induced coagulopathy and Japanese Association for Acute Medicine DIC in coagulopathic patients with decreased antithrombin and treated by antithrombin. Clin Appl Thromb Hemost 2018; 24 (07) 1020-1026
    CrossrefPubMedGoogle Scholar
  • 31 Iba T, Arakawa M, Di Nisio M. , 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 2018; 885066618773679
    PubMedGoogle Scholar