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

Kazuma Yamakawa; Jumpei Yoshimura; Takashi Ito; Mineji Hayakawa; Toshimitsu Hamasaki; Satoshi Fujimi

doi:10.1055/s-0038-1676610

Thrombosis and Haemostasis, Table of Contents

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

Authors

Kazuma Yamakawa

¹Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
Jumpei Yoshimura

¹Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan
Takashi Ito

²Department of Emergency and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Mineji Hayakawa

³Emergency and Critical Care Center, Hokkaido University Hospital, Sapporo, Japan
Toshimitsu Hamasaki

⁴Department of Biostatistics and Data Management, National Cerebral and Cardiovascular Center, Osaka, Japan
Satoshi Fujimi

¹Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan

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

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References

References
1 Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med 2015; 372 (09) 793-795
2 Jameson JL, Longo DL. Precision medicine--personalized, problematic, and promising. N Engl J Med 2015; 372 (23) 2229-2234
3 Vincent JL. The coming era of precision medicine for intensive care. Crit Care 2017; 21 (Suppl. 03) 314
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
20 Lyons PG, Micek ST, Hampton N, Kollef MH. Sepsis-associated coagulopathy severity predicts hospital mortality. Crit Care Med 2018; 46 (05) 736-742
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
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
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
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
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
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
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
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
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
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
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

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