Antithrombin in Burn Trauma

  • P. Enkhbaatar
  • L. D. Traber
  • D. L. Traber


In the United States, more than 1 million burn injuries occur every year. Although the survival from burn injury has increased in recent years with the development of effective fluid resuscitation management and early surgical excision of burned tissue, the mortality of burn injury is still high. In these fire victims, progressive pulmonary failure and cardiovascular dysfunction are important determinants of morbidity and mortality. The morbidity and mortality increases when burn injury is associated with smoke inhalation. Smoke inhalation and pneumonia increase mortality of burn patients by 20 and 40%, respectively [1], suggesting that the pulmonary involvement is a very important risk factor in burn trauma. Our group and others have reported various factors that are involved in pathophysiology of acute lung injury (ALI) in burn, including coagulopathy [2, 3]. It was earlier described that burn injury is associated with a hypercoagulable state [4]. The coagulopathy seen in these burn patients is associated with marked depletion of a major endogenous regulator of blood coagulation, antithrombin [3]–[5]. In the present chapter, we will discuss a possible role of antithrombin in the pathophysiology of ALI induced by combined burn and smoke inhalation and review the therapeutic approaches.


Severe Sepsis Acute Lung Injury Blood Coagul Fibrinolysis Smoke Inhalation Injury Fire Victim 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Barrow RE, Spies M, Barrow LN, Herndon DN (2004) Influence of demographics and inhalation injury on burn mortality in children. Burns 30:72–77PubMedCrossRefGoogle Scholar
  2. 2.
    Enkhbaatar P, Murakami K, Shimoda K, et al (2003) The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury. Am J Respir Crit Care Med 167:1021–1026PubMedCrossRefGoogle Scholar
  3. 3.
    Kowal-Vern A, Walenga JM, McGill V, Gameli RL (2001) The impact of antithrombin (H) concentrate infusions on pulmonary function in the acute phase of thermal injury. Burns 27: 52–60PubMedCrossRefGoogle Scholar
  4. 4.
    Kowal-Vern A, McGill V, Walenga JM, Gameli RL (2000) Antithrombin III concentrate in the acute phase of thermal injury. Burns 26:97–101PubMedCrossRefGoogle Scholar
  5. 5.
    Garcia-Avello A, Lorente JA, Cesar-Perez J, et al (1998) Hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma. Thromb Res 89:59–64PubMedCrossRefGoogle Scholar
  6. 6.
    Olson ST, Bjork I, Shore JD (1993) Kinetic characterization of heparin-catalyzed and uncatalyzed inhibition of blood coagulation proteinases by antithrombin. Methods Enzymol 222:525–559PubMedCrossRefGoogle Scholar
  7. 7.
    Olson ST, Bjork I (1991) Predominant contribution of surface approximation to the mechanism of heparin acceleration of the antithrombin-thrombin reaction. Elucidation from salt concentration effects. J Biol Chem 266:6353–6364PubMedGoogle Scholar
  8. 8.
    Olson ST, Bjork I, Sheffer R, Craig PA, Shore JD, Choay J (1992) Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. J Biol Chem 267:12528–12538PubMedGoogle Scholar
  9. 9.
    Justus AC, Roussev R, Norcross JL, Faulk WP (1995) Antithrombin binding by human umbilical vein endothelial cells: effects of exogenous heparin. Thromb Res 79:175–186PubMedCrossRefGoogle Scholar
  10. 10.
    Wu YI, Sheffield WP, Blajchman MA (1994) Defining the heparin-binding domain of antithrombin. Blood Coagul Fibrinolysis 5:83–95PubMedCrossRefGoogle Scholar
  11. 11.
    Swedenborg J (1998) The mechanisms of action of alpha-and beta-isoforms of antithrombin. Blood Coagul Fibrinolysis 9:S7–S10PubMedGoogle Scholar
  12. 12.
    Becker BF, Heindl B, Kupatt C, Zahler S (2000) Endothelial function and hemostasis. Z Kardiol 89:160–167PubMedGoogle Scholar
  13. 13.
    Senden NH, Jeunhomme TM, Heemskerk JW, et al (1998) Factor Xa induces cytokine production and expression of adhesion molecules by human umbilical vein endothelial cells. J Immunol 161:4318–4324PubMedGoogle Scholar
  14. 14.
    Coughlin SR (1999) How the protease thrombin talks to cells. Proc Natl Acad Sci USA 96: 11023PubMedCrossRefGoogle Scholar
  15. 15.
    Coughlin SR (2001) Protease-activated receptors in vascular biology. Thromb Haemost 86: 298–307PubMedGoogle Scholar
  16. 16.
    Esmon C (2000) The protein C pathway. Crit Care Med 28:S44–S48PubMedCrossRefGoogle Scholar
  17. 17.
    Liu I, Schuff-Werner P, Steiner M (2006) Thrombin/thrombin receptor (PAR-1)-mediated induction of IL-8 and VEGF expression in prostate cancer cells. Biochem Biophys Res Commun 343:183–189PubMedCrossRefGoogle Scholar
  18. 18.
    Okajima K, Uchiba M (1998) The anti-inflammatory properties of antithrombin III: new therapeutic implications. Semin Thromb Hemost 24:27–32PubMedCrossRefGoogle Scholar
  19. 19.
    Souter, PJ, Thomas S, Hubbard AR, et al (2001) Antithrombin inhibits lipopolysaccharide-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med. 29:134–139PubMedCrossRefGoogle Scholar
  20. 20.
    Kaneider NC, Egger P, Dunzendorfer S, Wiedermann C (2001) Syndecan-4 as antithrombin receptor of human neutrophils. Biochem Biophys Res Commun 287:42–46PubMedCrossRefGoogle Scholar
  21. 21.
    Soejima K, Schmalstieg FC, Sakurai H, Traber LD, Traber DL (2001) Pathophysiological analysis of combined burn and smoke inhalation injuries in sheep. Am J Physiol Lung Cell Mol Physiol 280:L1233–L1241PubMedGoogle Scholar
  22. 22.
    Enkhbaatar P, Traber DL (2004) Pathophysiology of acute lung injury in combined burn and smoke inhalation injury. Clin Sci (Lond) 107:137–143PubMedCrossRefGoogle Scholar
  23. 23.
    Aoki K, Aikawa N, Sekine K, et al (2001) Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burns. Burns 27:569–575PubMedCrossRefGoogle Scholar
  24. 24.
    Enkhbaatar P, Murakami K, Cox R, et al (2004) Aerosolized tissue plasminogen activator improves pulmonary function in sheep with burn and smoke inhalation. Shock 22:70–75PubMedCrossRefGoogle Scholar
  25. 25.
    Murakami K, McGuire R, Cox RA, et al (2003) Recombinant antithrombin attenuates pulmonary inflammation following smoke inhalation and pneumonia in sheep. Crit Care Med 31: 577–583PubMedCrossRefGoogle Scholar
  26. 26.
    Murakami K, Enkhbaatar P, Shimoda K, et al (2003) High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep. Clin Sci (Lond) 104:349–356PubMedCrossRefGoogle Scholar
  27. 27.
    Enkhbaatar P, Murakami K, Westphal M, et al (2004) Combined antithrombin and heparin nebulization improves pulmonary function in sheep with burn and smoke inhalation Crit Care Med 32:A24 (abst)Google Scholar
  28. 28.
    Enkhbaatar P, Traber L, Nakano Y, et al (2006) Effects of intravenously administered recombinant human antithrombin (rhAT) and aerosolized heparin on burn and smoke inhalation-induced acute lung injury. XIII Congress of the International Society for Burn Injuries, p 216 (abst)Google Scholar
  29. 29.
    Murakami K, McGuire R, Cox RA, et al (2002) Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep. Shock 18:236–241PubMedCrossRefGoogle Scholar
  30. 30.
    Warren B, Eid A, Singer P, et al (2001) High-dose antithrombin III in severe sepsis. A randomized controlled trial. JAMA 286:1869–1878PubMedCrossRefGoogle Scholar
  31. 31.
    Wiedermann CJ, Hoffmann JN, Juers M, et al (2006) High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: Efficacy and safety. Crit Care Med 34:285–292PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media Inc. 2007

Authors and Affiliations

  • P. Enkhbaatar
    • 1
  • L. D. Traber
    • 1
  • D. L. Traber
    • 1
  1. 1.Department of AnesthesiologyUniversity of Texas Medical BranchGalvestonUSA

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