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Prognostic value of sepsis-induced coagulation abnormalities: an early assessment in the emergency department

  • Francesca Innocenti
  • Anna Maria Gori
  • Betti Giusti
  • Camilla Tozzi
  • Chiara Donnini
  • Federico Meo
  • Irene Giacomelli
  • Maria Luisa Ralli
  • Alice Sereni
  • Elena Sticchi
  • Michela Zari
  • Francesca Caldi
  • Irene Tassinari
  • Maurizio Zanobetti
  • Rossella Marcucci
  • Riccardo Pini
EM - ORIGINAL

Abstract

To evaluate if the assessment of coagulation abnormalities at ED admission could improve prognostic assessment of septic patients. This report utilizes a portion of the data collected in a prospective study, with the aim to identify reliable biomarkers for an early sepsis diagnosis. In the period November 2011–December 2016, we enrolled 268 patients, admitted to our High-Dependency Unit with a diagnosis severe sepsis/septic shock. Study-related blood samplings were performed at ED-HDU admission (T0), after 6 h (T6) and 24 h (T24): D-dimer, thrombin–antithrombin complex (TAT) and prothrombin fragment F1 + 2 levels were analyzed. The primary end-points were day-7 and in-hospital mortality. Day-7 mortality rate was 16%. D-dimer (T0: 4661 ± 4562 µg/ml vs 3190 ± 7188 µg/ml; T6: 4498 ± 4931 µg/ml vs 2822 ± 5623 µg/ml; T24 2905 ± 2823 µg/ml vs 2465 ± 4988 µg/ml, all p < 0.05) and TAT levels (T0 29 ± 45 vs 22 ± 83; T6 21 ± 22 vs 15 ± 35; T24 16 ± 19 vs 13 ± 30, all p < 0.05) were higher among non-survivors compared to survivors. We defined an abnormal coagulation activation (COAG+) as D-dimer > 500 µg/ml and TAT > 8 ng/ml (for both, twice the upper normal value). Compared to COAG−, COAG+ patients showed higher lactate levels at the earliest evaluations (T0: 3.3 ± 2.7 vs 2.5 ± 2.3, p = 0.041; T6: 2.8 ± 3.4 vs 1.8 ± 1.6, p = 0.015); SOFA score was higher after 24 h (T24: 6.7 ± 3.1 vs 5.4 ± 2.9, p = 0.008). At T0, COAG+ patients showed a higher day-7 mortality rate (HR 2.64; 95% CI 1.14–6.11, p = 0.023), after adjustment for SOFA score and lactate level. Presence of abnormal coagulation at ED admission shows an independent association with an increased short-term mortality rate.

Keywords

Sepsis Coagulation abnormalities Prognostic stratification 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

The study was conducted in compliance with the Declaration of Helsinki at the Careggi University Hospital.

Informed consent

The study protocol was approved by the local Ethics Committee, and all subjects provided oral.

References

  1. 1.
    Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF (2004) Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 8(2):R82–R90.  https://doi.org/10.1186/cc2459 CrossRefGoogle Scholar
  2. 2.
    Collins PW, Macchiavello LI, Lewis SJ, Macartney NJ, Saayman AG, Luddington R, Baglin T, Findlay GP (2006) Global tests of haemostasis in critically ill patients with severe sepsis syndrome compared to controls. Br J Haematol 135(2):220–227.  https://doi.org/10.1111/j.1365-2141.2006.06281.x CrossRefGoogle Scholar
  3. 3.
    Koyama K, Madoiwa S, Nunomiya S, Koinuma T, Wada M, Sakata A, Ohmori T, Mimuro J, Sakata Y (2014) Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study. Crit Care 18(1):R13.  https://doi.org/10.1186/cc13190 CrossRefGoogle Scholar
  4. 4.
    Levi M, van der Poll T (2017) Coagulation and sepsis. Thromb Res 149:38–44.  https://doi.org/10.1016/j.thromres.2016.11.007 CrossRefGoogle Scholar
  5. 5.
    Angstwurm MW, Dempfle CE, Spannagl M (2006) 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 34(2):314–320 (00003246-200602000-00005 [pii]) CrossRefGoogle Scholar
  6. 6.
    Schwameis M, Steiner MM, Schoergenhofer C, Lagler H, Buchtele N, Jilma-Stohlawetz P, Boehm T, Jilma B (2015) D-dimer and histamine in early stage bacteremia: a prospective controlled cohort study. Eur J Intern Med 26(10):782–786.  https://doi.org/10.1016/j.ejim.2015.10.024 CrossRefGoogle Scholar
  7. 7.
    Adamik B, Gozdzik W, Jakubczyk D, Welna M, Kubler A (2017) Coagulation abnormalities identified by thromboelastometry in patients with severe sepsis: the relationship to endotoxemia and mortality. Blood Coagul Fibrinolysis 28(2):163–170.  https://doi.org/10.1097/mbc.0000000000000572 CrossRefGoogle Scholar
  8. 8.
    Innocenti F, Bianchi S, Guerrini E, Vicidomini S, Conti A, Zanobetti M, Pini R (2014) Prognostic scores for early stratification of septic patients admitted to an emergency department-high dependency unit. Eur J Emerg Med 21(4):254–259.  https://doi.org/10.1097/mej.0000000000000075 CrossRefGoogle Scholar
  9. 9.
    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 31(4):1250–1256.  https://doi.org/10.1097/01.ccm.0000050454.01978.3b CrossRefGoogle Scholar
  10. 10.
    Bakhtiari K, Meijers JC, de Jonge E, Levi M (2004) Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med 32(12):2416–2421 (00003246-200412000-00008 [pii]) CrossRefGoogle Scholar
  11. 11.
    Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abouhamze A, Pribble JP, Moldawer LL (2005) Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock 23(6):488–493 (00024382-200506000-00002 [pii]) Google Scholar
  12. 12.
    Shapiro NI, Schuetz P, Yano K, Sorasaki M, Parikh SM, Jones AE, Trzeciak S, Ngo L, Aird WC (2010) The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Crit Care 14(5):R182.  https://doi.org/10.1186/cc9290 CrossRefGoogle Scholar
  13. 13.
    Genga KR, Shimada T, Boyd JH, Walley KR, Russell JA (2018) The understanding and management of organism toxicity in septic shock. J Innate Immun.  https://doi.org/10.1159/000487818 CrossRefGoogle Scholar
  14. 14.
    Levi M, Poll T (2015) Coagulation in patients with severe sepsis. Semin Thromb Hemost 41(1):9–15.  https://doi.org/10.1055/s-0034-1398376 CrossRefGoogle Scholar
  15. 15.
    Couto-Alves A, Wright VJ, Perumal K, Binder A, Carrol ED, Emonts M, de Groot R, Hazelzet J, Kuijpers T, Nadel S, Zenz W, Ramnarayan P, Levin M, Coin L, Inwald DP (2013) A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis. Crit Care 17(2):R68.  https://doi.org/10.1186/cc12609 CrossRefGoogle Scholar
  16. 16.
    Benediktsson S, Frigyesi A, Kander T (2017) Routine coagulation tests on ICU admission are associated with mortality in sepsis: an observational study. Acta Anaesthesiol Scand 61(7):790–796.  https://doi.org/10.1111/aas.12918 CrossRefGoogle Scholar
  17. 17.
    Wang JY, Chen YX, Guo SB, Mei X, Yang P (2016) Predictive performance of quick Sepsis-related Organ Failure Assessment for mortality and ICU admission in patients with infection at the ED. Am J Emerg Med 34(9):1788–1793.  https://doi.org/10.1016/j.ajem.2016.06.015 CrossRefGoogle Scholar
  18. 18.
    Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286(14):1754–1758 (jce00056 [pii]) CrossRefGoogle Scholar
  19. 19.
    Jones AE, Trzeciak S, Kline JA (2009) The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit Care Med 37(5):1649–1654.  https://doi.org/10.1097/ccm.0b013e31819def97 CrossRefGoogle Scholar
  20. 20.
    Innocenti F, Tozzi C, Donnini C, De VE, Conti A, Zanobetti M, Pini R (2017) SOFA score in septic patients: incremental prognostic value over age, comorbidities, and parameters of sepsis severity. Intern Emerg Med.  https://doi.org/10.1007/s11739-017-1629-5 CrossRefGoogle Scholar

Copyright information

© Società Italiana di Medicina Interna 2018

Authors and Affiliations

  • Francesca Innocenti
    • 1
  • Anna Maria Gori
    • 2
  • Betti Giusti
    • 2
  • Camilla Tozzi
    • 1
  • Chiara Donnini
    • 1
  • Federico Meo
    • 1
  • Irene Giacomelli
    • 1
  • Maria Luisa Ralli
    • 1
  • Alice Sereni
    • 2
  • Elena Sticchi
    • 2
  • Michela Zari
    • 1
  • Francesca Caldi
    • 1
  • Irene Tassinari
    • 1
  • Maurizio Zanobetti
    • 1
  • Rossella Marcucci
    • 2
  • Riccardo Pini
    • 1
  1. 1.High-Dependency Unit, Department of Clinical and Experimental MedicineAzienda Ospedaliero-Universitaria CareggiFlorenceItaly
  2. 2.Department of Clinical and Experimental MedicineUniversity of FlorenceFlorenceItaly

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