Skip to main content

Advertisement

SpringerLink
Log in

Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock

  • Review
  • Published:
Critical Care Aims and scope Submit manuscript

Abstract

Knowing the pathophysiology of trauma-induced coagulopathy is important for the management of severely injured trauma patients. The aims of this review are to provide a summary of the recent advances in our understanding of thrombosis and hemostasis following trauma and to discuss the pathogenesis of disseminated intravascular coagulation (DIC) at an early stage of trauma. Local hemostasis and thrombosis respectively act to induce physiological wound healing of injuries and innate immune responses to damaged-self following trauma. However, if overwhelmed by systemic inflammation caused by extensive tissue damage and tissue hypoperfusion, both of these processes foster systemic DIC associated with pathological fibrin(ogen)olysis. This is called DIC with the fibrinolytic phenotype, which is characterized by the activation of coagulation, consumption coagulopathy, insufficient control of coagulation, and increased fibrin(ogen)olysis. Irrespective of microvascular thrombosis, the condition shows systemic thrombin generation as well as its activation in the circulation and extensive damage to the microvasculature endothelium. DIC with the fibrinolytic phenotype gives rise to oozing-type non-surgical bleeding and greatly affects the prognosis of trauma patients. The coexistences of hypothermia, acidosis, and dilution aggravate DIC and lead to so-called trauma-induced coagulopathy.

He that would know what shall be must consider what has been.

The Analects of Confucius.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

Abbreviations

ACOTS:

Acute coagulopathy of trauma shock

APTT:

Activated partial thromboplastin time

C4bBP:

C4b-binding protein

DAMP:

Damage-associated molecular pattern

DIC:

Disseminated intravascular coagulation

EPCR:

Endothelial protein C receptor

HMGB1:

High-mobility group box 1

IL:

Interleukin

ISTH:

International Society on Thrombosis and Haemostasis

JAAM:

Japanese Association for Acute Medicine

MODS:

Multiple organ dysfunction syndrome

NET:

Neutrophil extracellular trap

PAI-1:

Plasminogen activator inhibitor-1

PAMP:

Pathogen-associated molecular pattern

PF1 + 2:

Prothrombin fragment 1 + 2

PT:

Prothrombin time

SIRS:

Systemic inflammatory response syndrome

SSC:

Scientific and Standardization Committee

TAT:

Thrombin antithrombin complex

TFPI:

Tissue factor pathway inhibitor

TNF-α:

Tumor necrosis factor α

t-PA:

Tissue-type plasminogen activator

VWF:

von Willebrand factor

References

  1. Spero JA, Lewis JH, Hasiba U. Disseminated intravascular coagulation. Findings in 346 patients. Thromb Haesmost. 1980;43:28–33.

    CAS  Google Scholar 

  2. Marder VJ, Feinstein DI, Colman RW, Levi M. Consumptive thrombohemorrhagic disorders. In Hemostasis and Thrombosis. Basic Principles and Clinical Practice. 5th edition. Edited by Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ. Philadelphia: Lippincott Williams & Wilkins; 2006;1571–1600.

  3. Engelmann B, Massberg S. Thrombosis and intravascular effector of innate immunity. Nat Rev Immunol. 2013;13:34–45.

    CAS  PubMed  Google Scholar 

  4. Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, Kluger Y, et al. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008;65:748–54.

    CAS  PubMed  Google Scholar 

  5. Maegele M, Schöchl H, Cohen MJ. An up-date on the coagulopathy of trauma. Shock. 2014;41:21–5.

    CAS  PubMed  Google Scholar 

  6. Gando S, Sawamura S, Hayakawa M. Trauma, shock, and disseminated intravascular coagulation. Ann Surg. 2011;254:10–9.

    PubMed  Google Scholar 

  7. Gando S, Wada H, Kim HK, Kurosawa S, Nielsen JD, Thachil J, et al. Comparison of disseminated intravascular coagulation in trauma with coagulopathy of trauma/acute coagulopathy of trauma-shock. J Thromb Haemost. 2012;10:2593–5.

    CAS  PubMed  Google Scholar 

  8. Gando S, Wada H, Thachil J. Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS). J Thromb Haemost. 2013;11:826–35.

    CAS  PubMed  Google Scholar 

  9. Kutcher ME, Ferguson AR, Cohen MJ. A principle component analysis of coagulation after trauma. J Trauma Acute Care Surg. 2013;74:1223–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Castellheim A, Brekke OL, Espevik T, Harboe M, Mollnes TE. Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis. Scand J Immunol. 2009;69:479–91.

    CAS  PubMed  Google Scholar 

  11. Esmon CT. Inflammation and thrombosis. J Thromb Haemost. 2003;1:1343–8.

    CAS  PubMed  Google Scholar 

  12. Esmon CT, Xu J, Lupu F. Innate immunity and coagulation. J Thromb Haemost. 2011;9:182–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Rivers RP, Hathaway WE, Weston W. The endotoxin-induced coagulant activity of human monocytes. Br J Haematol. 1975;30:311–6.

    CAS  PubMed  Google Scholar 

  14. Müller I, Klocke A, Alex M, Kotzsch M, Luther T, Morgenstern E, et al. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J. 2003;17:476–8.

    PubMed  Google Scholar 

  15. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CCM, et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330:362–6.

    CAS  PubMed  Google Scholar 

  16. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, et al. Extracellular DNA traps promote thrombosis. PNAS. 2010;107:15880–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Fuchs TA, Bhandari AA, Wanger DD. Histones induce rapid and profound thrombocytopenia in mice. Blood. 2011;118:3708–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 2011;118:1952–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Ammollo CT, Semeraro F, Xu J, Esmon NL, Esmon CT. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost. 2011;9:1795–803.

    CAS  PubMed  Google Scholar 

  20. von Brühl ML, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, et al. Monocytes, neutrophils, and platelet cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209:819–35.

    Google Scholar 

  21. Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. Complement and coagulation: strangers or partners in crime? TRENDS Immunol. 2007;28:184–92.

    CAS  PubMed  Google Scholar 

  22. Kannemeier C, Shibamiya A, Nakazawa F, Trusheim H, Ruppert C, Markart P, et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. PNAS. 2007;104:6388–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Rapaport SI, Rao VM. Initiation and regulation of tissue factor-dependent blood coagulation. Arterioscler Thromb. 1992;12:1111–21.

    CAS  PubMed  Google Scholar 

  24. Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S, Goosmann C, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16:887–96.

    CAS  PubMed  Google Scholar 

  25. Ishii H, Majerus PW. Thrombomodulin is present in human plasma and urine. J Clin Invest. 1985;76:2178–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ishii H, Uchiyama H, Kazama M. Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost. 1991;65:618–23.

    CAS  PubMed  Google Scholar 

  27. Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35:2191–5.

    CAS  PubMed  Google Scholar 

  28. Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost. 2001;85:958–65.

    CAS  PubMed  Google Scholar 

  29. Manson J, Thiemermann C, Brohi K. Trauma alarmins as activators of damage-induced inflammation. Br J Surg. 2012;99:12–20.

    CAS  PubMed  Google Scholar 

  30. Cohen MJ, Brohi K, Calfee CS, Rhan P, Chesebro BB, Christiaans SC, et al. Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion. Crit Care. 2009;13:R174.

    PubMed  PubMed Central  Google Scholar 

  31. Kutcher ME, Xu J, Vilardi RF, Ho C, Esmon CT, Cohen MJ. Extracellular histone release in response to traumatic injury: implications for compensatory role of activated protein C. J Trauma Acute Care Surg. 2012;73:1389–94.

    PubMed  Google Scholar 

  32. Abrams ST, Zhang N, Manson J, Liu T, Dart C, Baluwa F, et al. Circulating histones are mediators of trauma-associated lung injury. Am J Crit Care Med. 2013;187:160–9.

    CAS  Google Scholar 

  33. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ito T, Kawahara K, Nakamura T, Yamada S, Nakamura T, Abeyama K, et al. High-mobility group box 1 protein promotes development of microvascular thrombosis in rats. J Thromb Haemost. 2007;5:109–16.

    CAS  PubMed  Google Scholar 

  35. Gando S, Nakanishi Y, Tedo I. Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated intravascular coagulation: relationship to multiple organ dysfunction. Crit Care Med. 1995;23:1835–42.

    CAS  PubMed  Google Scholar 

  36. Xu J, Zhang X, Monestier M, Esmon NL, Esmon CT. Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol. 2011;187:2626–31.

    CAS  PubMed  Google Scholar 

  37. Esmon CT. Possible involvement of cytokines in diffuse intravascular coagulation and thrombosis. Clin Haematol. 1999;12:343–59.

    CAS  Google Scholar 

  38. Boehme MWJ, Deng Y, Raeth U, Bierhaus A, Ziegler R, Stremmel W, et al. Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies. Immunology. 1996;87:134–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–30.

    CAS  PubMed  Google Scholar 

  40. Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res. 2009;124:608–13.

    CAS  PubMed  Google Scholar 

  41. Bakhtiari K, Meijers JCM, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med. 2004;32:2416–21.

    PubMed  Google Scholar 

  42. Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, et al. Natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey. Crit Care Med. 2008;6:145–50.

    Google Scholar 

  43. Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, et al. Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma. Thromb Res. 2009;124:706–10.

    CAS  PubMed  Google Scholar 

  44. Oshiro A, Yanagida Y, Gando S, Henzan N, Takahashi I, Makise H. Hemostasis during the early stage of trauma: comparison with disseminated intravascular coagulation. Crit Care. 2014;18:R61.

    PubMed  PubMed Central  Google Scholar 

  45. Gando S, Nanzaki S, Morimoto Y, Ishitani T, Kemmotsu O. Tissue factor pathway inhibitor does not correlate with tissue-factor induced disseminated intravascular coagulation and multiple organ dysfunction syndrome in trauma patients. Crit Care Med. 2001;29:262–6.

    CAS  PubMed  Google Scholar 

  46. Petersen LC, Valentin S, Hedner U. Regulation of the extrinsic pathway system in health and disease: the role of factor VIIa and tissue factor pathway inhibitor. Thromb Res. 1995;79:1–47.

    CAS  PubMed  Google Scholar 

  47. Hayakawa M, Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, et al. Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. Surgery. 2011;149:221–30.

    PubMed  Google Scholar 

  48. Gando S, Nakanishi Y, Kameue T, Nanzaki S. Soluble thrombomodulin increases in patients with disseminated intravascular coagulation and in those with multiple organ dysfunction syndrome after trauma: role of neutrophil elastase. J Trauma. 1995;39:660–4.

    CAS  PubMed  Google Scholar 

  49. Ogawa S, Shreeniwas R, Butura C, Brett J, Stern DM. Modulation of endothelial function by hypoxia: perturbation of barrier and anticoagulant function, and induction of a novel factor X activator. Adv Exp Med Biol. 1990;281:303–12.

    CAS  PubMed  Google Scholar 

  50. Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D. Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties. J Clin Invest. 1990;85:1090–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Öhlin AK, Larsson K, Hansson M. Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma. J Thromb Haemost. 2005;3:976–82.

    PubMed  Google Scholar 

  52. Taylor FB, Chang A, Ferrell G, Mather T, Catlett R, Blick K, et al. C4b-binding protein exacerbates the host response to Escherichia coli. Blood. 1991;78:357–63.

    CAS  PubMed  Google Scholar 

  53. Engelman DT, Gabram SGA, Allen L, Ens GE, Jacobs LM. Hypercoagulability following multiple trauma. World J Surg. 1996;20:5–10.

    CAS  PubMed  Google Scholar 

  54. Liaw PCY, Ferrell G, Esmon CT. A monoclonal antibody against activated protein C allows rapid detection of activated protein C in plasma and reveals a calcium ion dependent epitope involved in factor Va inactivation. J Thromb Haemost. 2003;1:662–70.

    CAS  PubMed  Google Scholar 

  55. Cohen MJ, Call M, Nelson M, Calfee CS, Esmon CT, Brohi K, et al. Critical role of activated protein C in early coagulopathy and later organ failure, infection and death in trauma patients. Ann Surg. 2012;255:379–85.

    PubMed  Google Scholar 

  56. Butenas S, van’t Veer C, Mann KG. ‘Normal’ thrombin generation. Blood. 1999;94:2169–78.

    CAS  PubMed  Google Scholar 

  57. Grottke O, Braunschweig T, Spronk HMH, Esch S, Rieg AD, van Oerle R, et al. Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury. Blood. 2011;118:1943–51.

    CAS  PubMed  Google Scholar 

  58. Miller RS, Weatherford DA, Stein D, Crane MM, Stein M. Antithrombin III and trauma patients: factors that determine low levels. J Trauma. 1994;37:442–5.

    CAS  PubMed  Google Scholar 

  59. Liener UC, Brückner UB, Strecker W, Steinback G, Kinzl L, Gebhard F. Trauma severity-dependent changes in ATIII activity. Shock. 2001;15:344–7.

    CAS  PubMed  Google Scholar 

  60. Owings JT, Bagley M, Gosselin R, Romac D, Disbrow E. Effect of critical injury on plasma antithrombin activity: low antithrombin levels are associated with thromboembolic complications. J Trauma. 1996;41:396–406.

    CAS  PubMed  Google Scholar 

  61. Gando S, Tedo I, Kubota M. Posttrauma coagulation and fibrinolysis. Crit Care Med. 1992;20:594–600.

    CAS  PubMed  Google Scholar 

  62. Yanagida Y, Gando S, Hayakawa M, Sawamura A, Uegaki S, Kubota N, et al. Normal prothrombinase activity, increased systemic thrombin generation, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: comparison with acute coagulopathy of trauma-shock. Surgery. 2013;154:48–57.

    PubMed  Google Scholar 

  63. Dunbar NM, Chandler WL. Thrombin generation in trauma patients. Transfusion. 2009;49:2652–60.

    CAS  PubMed  Google Scholar 

  64. Chandler WL. Procoagulant activity in trauma patients. Am J Clin Pathol. 2010;134:90–6.

    PubMed  Google Scholar 

  65. Taylor FB. Responses of anticoagulant pathways in disseminated intravascular coagulation. Semin Thromb Haemost. 2001;27:619–31.

    CAS  Google Scholar 

  66. Gando S, Nanzaki S, Sasaki S, Kemmotsu O. Significant correlations between tissue factor and thrombin markers in trauma and septic patients with disseminated intravascular coagulation. Thromb Haemost. 1998;79:1111–5.

    CAS  PubMed  Google Scholar 

  67. Ogura H, Kawasaki T, Tanaka H, Koh T, Tanaka R, Ozeki Y, et al. Activated platelets enhance microparticle formation and platelet-leucocyte interaction in severe trauma and sepsis. J Trauma. 2001;50:801–9.

    CAS  PubMed  Google Scholar 

  68. Nakashima M, Uematsu T, Umemura K, Maruyama I, Tsuruta K. A novel recombinant human soluble thrombomodulin, ART-123, activates the protein C pathway in healthy male volunteers. J Clin Pharmacol. 1998;38:540–4.

    CAS  PubMed  Google Scholar 

  69. Mohri M, Sata M, Gomi K, Maruyama Y, Osame M, Maruyama I. Abnormalities in the protein C anticoagulant pathway detected by a novel assay using human thrombomodulin. Lupus. 1997;6:590–6.

    CAS  PubMed  Google Scholar 

  70. Giles AR, Nesheim ME, Mann KG. Studies of Factors V and VIII:C in an animal model of disseminated intravascular coagulation. J Clin Invest. 1984;74:2219–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Wyshock EG, Sufferendini AF, Parrillo JE, Colman RE. Cofactors V and VIII after endotoxin administration to human volunteers. Thromb Res. 1995;80:377–89.

    CAS  PubMed  Google Scholar 

  72. Hiippala S. Replacement of massive blood loss. Vox Sang. 1998;74:399–407.

    CAS  PubMed  Google Scholar 

  73. Lowenstein CJ, Morrell CN, Yamakuchi M. Regulation of Weibel-Palade body exocytosis. Trend Cardivasc Med. 2005;15:302–8.

    CAS  Google Scholar 

  74. Terraube V, O'Donnell JS, Jenkins PV. Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance. Haemophilia. 2010;16:3–13.

    CAS  PubMed  Google Scholar 

  75. Clarke BJ, Sridhara S, Woskowska Z, Blajchman MA. Consumption of plasma factor VII in a rabbit model of non-overt disseminated intravascular coagulation. Thromb Res. 2003;108:329–34.

    CAS  Google Scholar 

  76. Gando I, Makise H, Tedo I. Variation in wound healing factors in trauma patients. Jp J Surg. 1990;91:17–22.

    CAS  Google Scholar 

  77. McKay DG. Trauma and disseminated intravascular coagulation. J Trauma. 1969;9:646–60.

    CAS  PubMed  Google Scholar 

  78. Flute PT. Coagulation and fibrinolysis after injury. J Clin Pathol. 1970;23:102–9.

    Google Scholar 

  79. Risberg B. Fibrinolysis in trauma. Eur Surg Res. 1978;10:373–81.

    CAS  PubMed  Google Scholar 

  80. Raza I, Davenport R, Rourke C, Platton S, Manson J, Spoors C, et al. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost. 2013;11:307–14.

    CAS  PubMed  Google Scholar 

  81. Stump DC, Taylor FBJ, Nesheim ME, Giles AR, Dzik WH, Bovill EG. Pathologic fibrinolysis as a cause of clinical bleeding. Semin Thromb Hemost. 1990;16:260–73.

    CAS  PubMed  Google Scholar 

  82. Levi M, ten Cate H, van der Poll T, van Daventer SJH. Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA. 1993;270:975–9.

    CAS  PubMed  Google Scholar 

  83. Gando S, Kameue T, Nanzaki S, Nakanishi Y. Massive fibrin formation with consecutive impairment of fibrinolysis in patients with out-of-hospital cardiac arrest. Thromb Hemost. 1997;77:278–82.

    CAS  Google Scholar 

  84. Hayakawa M, Gando S, Ieko M, Honma Y, Homma T, Yanagida Y, et al. Massive amount of tissue factor induce fibrinogenolysis without tissue hypoperfusion in rats. Shock. 2013;39:514–9.

    CAS  PubMed  Google Scholar 

  85. Gando S. Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med. 2010;38:S35–42.

    PubMed  Google Scholar 

  86. Bergentz SE, Leandoer L. Disseminated intravascular coagulation in shock. Ann Chir Gynecol Fenn. 1971;60:175–9.

    CAS  Google Scholar 

  87. Turpini R, Stefanini M. The nature and mechanism of the hemostatic breakdown in the course of experimental hemorrhagic shock. J Clin Invest. 1959;38:53–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Borgström S, Gelin LE, Zederfeldt B. The formation of vein thrombi following tissue injury. An experimental study in rabbits. Act Chir Scand 1959;Suppl 247:1–36.

  89. Allardyce B, Hamit HF, Matsumoto T, Moseley RV. Pulmonary vascular changes in hypovolemic shock: radiography of the pulmonary microcirculation and the possible role of platelet embolism in increasing vascular resistance. J Trauma. 1999;9:403–11.

    Google Scholar 

  90. Lungqvist U, Bergentz SE, Lewis DH. The distribution of platelets, fibrin and erythrocytes in various organs following experimental trauma. Eur Surg Res. 1971;3:293–300.

    Google Scholar 

  91. Leandoer L, Bergentz SE. Haemorrhagic shock in the dog. The formation of thromboemboli during antifibrinolytic therapy. Eur Surg Res. 1970;2:341–7.

    CAS  PubMed  Google Scholar 

  92. Avikainen V, Eklund B. Disseminated intravascular coagulation after inhibition of fibrinolysis with tranexamic acid (AMCA) and proteinase inhibitor trasylol in experimental traumatic and haemorrhagic shock. Ann Chir Gynecol Fenn. 1974;63:226–34.

    CAS  Google Scholar 

  93. Hardaway RM. The significance of coagulative and thrombotic changes after haemorrhage and injury. J Clin Pathol (R Coll Pathol). 1970;4:110–20.

    CAS  Google Scholar 

  94. Nuytinck HK, Offermans XJ, Kubat K, Goris JA. Whole-body inflammation in trauma patients. An autopsy study. Arch Surg. 1988;123:1519–24.

    CAS  PubMed  Google Scholar 

  95. Rizoli S, Nascimento B, Key N, Tien HC, Muraca S, Pinto R, et al. Disseminated intravascular coagulopathy in the first 24 hours after trauma: the association between ISTH score and anatomopathologic evidence. J Trauma. 2011;71:S441–7.

    CAS  PubMed  Google Scholar 

  96. Parr MJ, Bouillon B, Brohi K, Dutton RP, Hauser CJ, Hess JR, et al. Traumatic coagulopathy: where are the good experimental models? J Trauma. 2008;65:766–71.

    PubMed  Google Scholar 

  97. Frith D, Cohen MJ, Brohi K. Animal models of trauma-induced coagulopathy. Thromb Res. 2012;129:551–6.

    CAS  PubMed  Google Scholar 

  98. Gentile LF, Nacionales DC, Cuenca AG, Armbruster MA, Ungaro RF, Abouhamze AS, et al. Identification and description of a novel murine model for polytrauma and shock. Crit Care Med. 2013;41:1075–85.

    PubMed  PubMed Central  Google Scholar 

  99. Tanabe K, Yoshitake J. A study on coagulation and fibrinolytic dynamics in experimental traumatic shock. Masui (Jp J Anesthesiol). 1981;30:826–31.

    CAS  Google Scholar 

  100. Kugimiya H. A pathophysiological and biochemical study on the experimental traumatic shock in rats. A relationship between coagulation/fibrinolytic system and DIC. Masui (Jp J Anesthesiol) 1982;31:75–84.

  101. Armstead VE, Opetanova IL, Minchenko AG, Lefer AM. Tissue factor expression in vital organs during murine traumatic shock. Anesthesiology. 1999;91:1844–52.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7, Kitaku, Sapporo, 060-8638, Japan

    Satoshi Gando

  2. Department of Acute Critical Care and Disaster Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyoku, Tokyo, 113-8510, Japan

    Yasuhiro Otomo

Authors
  1. Satoshi Gando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuhiro Otomo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoshi Gando.

Additional information

Competing interests

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gando, S., Otomo, Y. Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. Crit Care 19, 72 (2015). https://doi.org/10.1186/s13054-015-0735-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/s13054-015-0735-x

Keywords

Search

Navigation