Disseminated Intravascular Coagulation in Burn Injury

ABSTRACT

Disseminated intravascular coagulation (DIC) is a complex and multifaceted disorder characterized by the activation of coagulation and fibrinolytic pathways, consumption of coagulation factors, and depletion of coagulation regulatory proteins. The introduction into the circulation of cellular debris characterized by strong thromboplastic activity due to tissue factor exposition or release (in or from burned tissues), which can thereby activate extrinsic pathway of coagulation system and trigger massive thrombin generation when present in sufficient concentration, represents the most plausible biological explanation to support the development of intravascular coagulation in patients with burn injury. Severe burns left untreated might also lead to an immunological and inflammatory response (activation of the complement cascade), which can amplify fibrinolysis and blood clotting. Overall, the real prevalence of DIC in patients with burns is as yet unclear. Postmortem, retrospective, and even longitudinal investigations are in fact biased by several factors, such as the objective difficulty to establish whether DIC might have occurred as a primary complication of burns or rather as a consequence of other superimposed pathologies (e.g., sepsis, multiple organ failure), the different diagnostic criteria for assessing DIC, and the heterogeneity of the patient samples studied. Nevertheless, the current scientific evidence is consistent with the hypothesis that biochemical changes suggestive for DIC (hypercoagulability, hypo- and hyperfibrinolysis) are commonplace in patients with burn trauma, and their severity increases exponentially with the severity of injury. Overt DIC seems to occur especially in critically ill burn patients or in those with severe burns (up to third degree) and large involvement of body surface area, in whom an appropriate therapy might be effective to prevent the otherwise fulminant course. Although early prophylaxis with antithrombin concentrates holds promises, especially in the acute phase of thermal injury, larger clinical trials are needed to confirm the benefit of this therapeutic approach.

KEYWORDS

Burns - hemostasis - coagulation - disseminated intravascular coagulation

REFERENCES

• 1 Supple K G. Physiologic response to burn injury.  Crit Care Nurs Clin North Am. 2004;  16(1) 119-126
• 2 Sheridan R L. Burns.  Crit Care Med. 2002;  30(11, Suppl) S500-S514
• 3 American Burn Association .National Burn Repository 2009. Available at: http://www.ameriburn.org/2009NBRAnnualReport.pdf Accessed November 6, 2009
• 4 World Health Organization .Burn Fact Sheet. Available at: http://www.ameriburn.org/WHO-ISBIBurnFactsheet.pdf Accessed November 6, 2009
• 5 World Fire Statistics Centre .World Fire Statistics—October 2009. Available at: http://www.genevaassociation.org/Affiliated_Organizations/WFSC.aspx Accessed November 6, 2009
• 6 US Fire Administration .QuickStats: The Overall Fire Picture—2007. US Fire Administration Web site. Available at: http://www.usfa.fema.gov/statistics/quickstats/ Accessed November 6, 2009
• 7 Sevitt S. A review of the complications of burns, their origin and importance for illness and death.  J Trauma. 1979;  19(5) 358-369
• 8 Wassermann D. Systemic complications of extended burns [in French].  Ann Chir Plast Esthet. 2001;  46(3) 196-209
• 9 Mertens D M, Jenkins M E, Warden G D. Outpatient burn management.  Nurs Clin North Am. 1997;  32(2) 343-364
• 10 Serrano C, Acha B, Gómez-Cía T, Acha J I, Roa L M. A computer assisted diagnosis tool for the classification of burns by depth of injury.  Burns. 2005;  31(3) 275-281
• 11 Faucher L D, Conlon K M. Practice guidelines for deep venous thrombosis prophylaxis in burns.  J Burn Care Res. 2007;  28(5) 661-663
• 12 McManus W F, Eurenius K, Pruitt Jr B A. Disseminated intravascular coagulation in burned patients.  J Trauma. 1973;  13(5) 416-422
• 13 Bréan L, Bormioli M, Angela G C, Ferrari F. Coagulation disorders due to burns. Disseminated intravascular coagulation (DIC) and its possible prevention [in Italian].  Minerva Med. 1975;  66(55) 2729-2742
• 14 Zuckerman L, Caprini J A, Lipp V, Vagher J P. Disseminated intravascular multiple systems activation (DIMSA) following thermal injury.  J Trauma. 1978;  18(6) 432-439
• 15 Yoshioka T, Ikemura K, Sawada Y, Ohashi N, Sugimoto H, Sugimoto T. The causes of abnormal coagulation system in the early phase of burns [in Japanese].  Nippon Geka Gakkai Zasshi. 1983;  84(9) 886-890
• 16 Wells S, Sissons M, Hasleton P S. Quantitation of pulmonary megakaryocytes and fibrin thrombi in patients dying from burns.  Histopathology. 1984;  8(3) 517-527
• 17 Ueyama M, Yamamoto I, Sawada Y. Disseminated intravascular coagulation in the early stage after severe burn: the role of excessive thrombin generation [in Japanese].  Nippon Geka Gakkai Zasshi. 1991;  92(8) 907-912
• 18 Kowal-Vern A, Gamelli R L, Walenga J M, Hoppensteadt D, Sharp-Pucci M, Schumacher H R. The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state.  J Trauma. 1992;  33(1) 50-56 discussion 56-57
• 19 García-Avello A, Lorente J A, Cesar-Perez J et al.. Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma.  Thromb Res. 1998;  89(2) 59-64
• 20 Barret J P, Gomez P A. Disseminated intravascular coagulation: a rare entity in burn injury.  Burns. 2005;  31(3) 354-357
• 21 Lavrentieva A, Kontakiotis T, Bitzani M et al.. Early coagulation disorders after severe burn injury: impact on mortality.  Intensive Care Med. 2008;  34(4) 700-706
• 22 Vazina I R, Presniakova M V, Sidorkina A N. Intravascular morphological manifestations of the syndrome of disseminated intravascular coagulation (DIC) in the acute period of burn disease [in Russian].  Vestn Khir Im I I Grek. 2005;  164(6) 58-61
• 23 Guest M M, Bond T P. Release of thromboplastin after thermal injury.  Ann N Y Acad Sci. 1968;  150(3) 528-536
• 24 Ueyama M, Yamamoto I, Sawada Y. Disseminated intravascular coagulation in the early stage after severe burn: the role of excessive thrombin generation [in Japanese].  Nippon Geka Gakkai Zasshi. 1991;  92(8) 907-912
• 25 von Bülow S, Hartmann T, Fuchs P C, Schrimpf C, Pallua N. Endothelial thrombomodulin (CD 141) in a rabbit burn model.  Burns. 2005;  31(4) 459-464
• 26 Van de Wouwer M, Collen D, Conway E M. Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation.  Arterioscler Thromb Vasc Biol. 2004;  24(8) 1374-1383
• 27 Aoki K, Aikawa N, Sekine K et al.. Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burns.  Burns. 2001;  27(6) 569-575
• 28 Kaloudová Y, Lipový B, Zaloudíková Z et al.. International Society on Thrombosis and Haemostasis: disseminated intravascular coagulation score in burns [Abstract].  Burns. 2009;  35(Suppl 1) S46
• 29 Ravindranath T M, Goto M, Demir M et al.. Tissue factor pathway inhibitor and thrombin activatable fibrinolytic inhibitor plasma levels following burn and septic injuries in rats.  Clin Appl Thromb Hemost. 2004;  10(4) 379-385
• 30 Niemi T, Svartling N, Syrjälä M, Asko-Seljavaara S, Rosenberg P. Haemostatic disturbances in burned patients during early excision and skin grafting.  Blood Coagul Fibrinolysis. 1998;  9(1) 19-28
• 31 Kowal-Vern A, Sharp-Pucci M M, Walenga J M, Dries D J, Gamelli R L. Trauma and thermal injury: comparison of hemostatic and cytokine changes in the acute phase of injury.  J Trauma. 1998;  44(2) 325-329
• 32 Nurden A T, Bihour C, Macchi L et al.. Platelet activation in thrombotic disorders.  Nouv Rev Fr Hematol. 1993;  35(1) 67-71
• 33 Lupia E, Bosco O, Mariano F et al.. Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation.  J Thromb Haemost. 2009;  7(6) 1000-1008
• 34 Kowal-Vern A, McGill V, Walenga J M, Gamelli R L. Antithrombin(H) concentrate infusions are safe and effective in patients with thermal injuries.  J Burn Care Rehabil. 2000;  21(2) 115-127
• 35 Lavrentieva A, Kontakiotis T, Bitzani M et al.. The efficacy of antithrombin administration in the acute phase of burn injury.  Thromb Haemost. 2008;  100(2) 286-290
• 36 Kowal-Vern A, Walenga J M, McGill V, Gamelli R L. The impact of antithrombin (H) concentrate infusions on pulmonary function in the acute phase of thermal injury.  Burns. 2001;  27(1) 52-60
• 37 Kowal-Vern A, Latenser B A. Antithrombin (human) concentrate infusion in pediatric patients with >50% TBSA burns.  Burns. 2003;  29(6) 615-618
• 38 Del Principe D. Antithrombin III in burned children [in Italian].  Minerva Anestesiol. 2003;  69(5) 376-380
• 39 Franchini M, Lippi G, Guidi G C. The use of recombinant activated factor VII in platelet-associated bleeding.  Hematology. 2008;  13(1) 41-45
• 40 Franchini M, Lippi G. Acquired factor VIII inhibitors.  Blood. 2008;  112(2) 250-255
• 41 Franchini M, Franchi M, Bergamini V, Salvagno G L, Montagnana M, Lippi G. A critical review on the use of recombinant factor VIIa in life-threatening obstetric postpartum hemorrhage.  Semin Thromb Hemost. 2008;  34(1) 104-112
• 42 Franchini M, Manzato F, Salvagno G L, Lippi G. Potential role of recombinant activated factor VII for the treatment of severe bleeding associated with disseminated intravascular coagulation: a systematic review.  Blood Coagul Fibrinolysis. 2007;  18(7) 589-593
• 43 Martin J T, Alkhoury F, McIntosh B C, Fidler P, Schulz J. Recombinant factor VIIa: hemostatic adjunct in the coagulopathic burn patient.  Eplasty. 2009;  9 e27
• 44 Greenhalgh D G, Gamelli R L, Collins J et al.. Recombinant thrombin: safety and immunogenicity in burn wound excision and grafting.  J Burn Care Res. 2009;  30(3) 371-379