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Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy

Xavier Delabranche| Julie Boisramé-Helms| Pierre Asfar| Asaël Berger| Yoganaden Mootien| Thierry Lavigne| Lélia Grunebaum| François Lanza| Christian Gachet| Jean-Marie Freyssinet| Florence Toti| Ferhat Meziani
Seven-Day Profile Publication
Volume 39, Issue 10 / October , 2013

Pages 1695 - 1703

Abstract

Purpose

Septic shock-induced disseminated intravascular coagulopathy (DIC) contributes to multiple organ failure. Mechanisms governing vascular responses to open occurrence of DIC have not yet been established. Circulating plasma microparticles (MPs), released upon cell stress, constitute a catalytic procoagulant surface and are surrogates of vascular cell activation/injury. Herein, MPs were assessed as possible markers of haemostatic and vascular dysfunction in the DIC time course.

Methods

One hundred patients with septic shock from three ICUs were enrolled and their haemostatic status evaluated at admission (D1), D2, D3 and D7. Circulating procoagulant MPs were isolated, quantified by prothrombinase assay and their cellular origin determined. DIC diagnosis was made according to the JAAM 2006 score.

Results

Ninety-two patients were analysed and 40 had DIC during the first 24 h. Routine clotting times and factor/inhibitor activity did not allow assessing vascular cell involvement. At admission, thrombin generation and fibrinolysis were observed in both groups while impaired fibrin polymerisation was evidenced only in DIC patients. Sustained thrombin generation persisted over time in both groups at D7. While total microparticle concentrations were in the same range regardless of DIC diagnosis, specific phenotypes were already detected at admission in DIC patients. Endothelial- and leucocyte-derived MPs were higher in DIC while an increased soluble glycoprotein V/platelet ratio was delayed, underscoring the first involvement of endothelial cells and leucocytes whereas platelet activation was delayed. Endothelium-derived CD105-MPs (OR 6.55) and CD31-MPs (OR 0.49) were strongly associated with early DIC in multivariate analysis.

Conclusion

Endothelial-derived microparticles are relevant biomarkers of septic shock-induced DIC and could be used to evaluate early vascular injury.

Keywords

References

  1. Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78
    • View reference on PubMed
    • View reference on publisher's website
  2. Fourrier F (2012) Severe sepsis, coagulation, and fibrinolysis: dead end or one way? Crit Care Med 40:2704–2708
    • View reference on PubMed
    • View reference on publisher's website
  3. Levi M (2012) Coagulation and sepsis: a winding road ahead. Crit Care Med 40:2733–2734
    • View reference on PubMed
    • View reference on publisher's website
  4. Gando S (2010) Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med 38:S35–S42
    • View reference on PubMed
    • View reference on publisher's website
  5. Gando S, Wada H, Tachil J; The Scientific Standardization Committee on DIC of the International Society on Thrombosis and Haemostasis (ISTH) (2013) Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS). J Thromb Haemost 11:826–835
    • View reference on publisher's website
  6. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M (2001) Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 86:1327–1330
    • View reference on PubMed
  7. Gando S, Iba T, Eguchi Y, Ohtomo Y, Okamoto K, Koseki K, Mayumi T, Murata A, Ikeda T, Ishikura H, Ueyama M, Ogura H, Kushimoto S, Saitoh D, Endo S, Shimazaki S (2006) A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med 34:625–631
    • View reference on PubMed
  8. 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 32:2416–2421
    • View reference on PubMed
    • View reference on publisher's website
  9. Singh RK, Baronia AK, Sahoo JN, Sharma S, Naval R, Pandey CM, Poddar B, Azim A, Gurjar M (2012) 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 129:e119–e125
    • View reference on PubMed
    • View reference on publisher's website
  10. Wada H, Thachil J, Di Nisio M, Mathew P, Kurosawa S, Gando S, Kim HK, Nielsen JD, Dempfle CE, Levi M, Toh CH; The Scientific Standardization Committee on DIC of the International Society on Thrombosis and Haemostasis (2013) Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost 11:761–767
    • View reference on publisher's website
  11. Boisramé-Helms J, Kremer H, Schini-Kerth V, Meziani F (2013) Endothelial dysfunction in sepsis. Curr Vasc Pharmacol 11:150–160
    • View reference on PubMed
  12. Meziani F, Tesse A, Andriantsitohaina R (2008) Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases. Pharmacol Rep 60:75–84
    • View reference on PubMed
  13. Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 107:1047–1057
    • View reference on PubMed
    • View reference on publisher's website
  14. Meziani F, Delabranche X, Asfar P, Toti F (2010) Bench-to-bedside review: circulating microparticles a new player in sepsis? Crit Care 14:236
    • View reference on PubMed
    • View reference on publisher's website
  15. Delabranche X, Berger A, Boisramé-Helms J, Meziani F (2012) Microparticles and infectious diseases. Med Mal Infect 42:335–343
    • View reference on PubMed
    • View reference on publisher's website
  16. Schouten M, Wiersinga WJ, Levi M, van der Poll T (2008) Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol 83:536–545
    • View reference on PubMed
    • View reference on publisher's website
  17. Joop K, Berckmans RJ, Nieuwland R, Berkhout J, Romijn FP, Hack CE, Sturk A (2001) Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms. Thromb Haemost 85:810–820
    • View reference on PubMed
  18. Perez-Casal M, Thompson V, Downey C, Welters I, Wyncoll D, Thachil J, Toh CH (2011) The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis. Crit Care 15:R195
    • View reference on PubMed
    • View reference on publisher's website
  19. Mortaza S, Martinez MC, Baron-Menguy C, Burban M, De la Bourdonnaye M, Fizanne L, Pierrot M, Cales P, Henrion D, Andriantsitohaina R, Mercat A, Asfar P, Meziani F (2009) Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats. Crit Care Med 37:2045–2050
    • View reference on PubMed
    • View reference on publisher's website
  20. Zafrani L, Gerotziafas G, Byrnes C, Hu X, Perez J, Levi C, Placier S, Letavernier E, Leelahavanichkul A, Haymann JP, Elalamy I, Miller JL, Star RA, Yuen PS, Baud L (2012) Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release. Am J Respir Crit Care Med 185:744–755
    • View reference on PubMed
    • View reference on publisher's website
  21. Reid VL, Webster NR (2012) Role of microparticles in sepsis. Br J Anaesth 109:503–513
    • View reference on PubMed
    • View reference on publisher's website
  22. 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. Intensive Care Med 29:530–538
  23. Hugel B, Zobairi F, Freyssinet JM (2004) Measuring circulating cell-derived microparticles. J Thromb Haemost 2:1846–1847
    • View reference on publisher's website
  24. Bakouboula B, Morel O, Faure A, Zobairi F, Jesel L, Trinh A, Zupan M, Canuet M, Grunebaum L, Brunette A, Desprez D, Chabot F, Weitzenblum E, Freyssinet JM, Chaouat A, Toti F (2008) Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. Am J Respir Crit Care Med 177:536–543
    • View reference on PubMed
    • View reference on publisher's website
  25. 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 14:13
    • View reference on publisher's website
  26. Levi M, de Jonge E, van der Poll T (2003) Sepsis and disseminated intravascular coagulation. J Thromb Thrombolysis 16:43–47
    • View reference on PubMed
    • View reference on publisher's website
  27. Levi M (2010) The coagulant response in sepsis and inflammation. Hamostaseologie 30(10–12):14–16
  28. Kushimoto S, Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, Ishikura H, Iba T, Ueyama M, Eguchi Y, Otomo Y, Okamoto K, Endo S, Shimazaki S (2008) Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria. Comparison between sepsis and trauma. Thromb Haemost 100:1099–1105
    • View reference on PubMed
  29. Takemitsu T, Wada H, Hatada T, Ohmori Y, Ishikura K, Takeda T, Sugiyama T, Yamada N, Maruyama K, Katayama N, Isaji S, Shimpo H, Kusunoki M, Nobori T (2011) Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation. Thromb Haemost 105:40–44
    • View reference on PubMed
    • View reference on publisher's website
  30. Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K (2004) Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol 76:225–229
    • View reference on PubMed
    • View reference on publisher's website
  31. Nieuwland R, Berckmans RJ, McGregor S, Boing AN, Romijn FP, Westendorp RG, Hack CE, Sturk A (2000) Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 95:930–935
    • View reference on PubMed
  32. Osterud B (2010) Tissue factor expression in blood cells. Thromb Res 125:S31–S34
    • View reference on PubMed
    • View reference on publisher's website
  33. Van Der Meijden PE, Van Schilfgaarde M, Van Oerle R, Renne T, ten Cate H, Spronk HM (2012) Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 10:1355–1362
    • View reference on publisher's website
  34. Heemskerk JW, Mattheij NJ, Cosemans JM (2013) Platelet-based coagulation: different populations, different functions. J Thromb Haemost 11:2–16
    • View reference on PubMed
    • View reference on publisher's website
  35. de Jong HK, van der Poll T, Wiersinga WJ (2010) The systemic pro-inflammatory response in sepsis. J Innate Immun 2:422–430
    • View reference on PubMed
    • View reference on publisher's website
  36. Ramma W, Ahmed A (2011) Is inflammation the cause of pre-eclampsia? Biochem Soc Trans 39:1619–1627
    • View reference on PubMed
    • View reference on publisher's website
  37. Dasgupta SK, Abdel-Monem H, Niravath P, Le A, Bellera RV, Langlois K, Nagata S, Rumbaut RE, Thiagarajan P (2009) Lactadherin and clearance of platelet-derived microvesicles. Blood 113:1332–1339
    • View reference on PubMed
    • View reference on publisher's website
  38. Mosnier LO, Zlokovic BV, Griffin JH (2007) The cytoprotective protein C pathway. Blood 109:3161–3172
    • View reference on PubMed
    • View reference on publisher's website

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