Advancing in the understanding of coagulopathy during hemorrhagic shock: From the triad to the deadly pentad

  • Manuel Quintana-Díaz Intensive Medicine Service, Hospital Universitario La Paz, Universidad Autónoma de Madrid. Madrid, Spain. https://orcid.org/0000-0003-4852-4148
  • Manuel Garay-Fernández a. Internal Medicine, Pulmonology and Intensive Care, Universidad El Bosque. Bogotá, Colombia. b. Internal Medicine, Pulmonology and Intensive Care, Hospital Santa Clara. Bogotá, Colombia. https://orcid.org/0000-0002-3249-6501
  • Fredy Ariza-Cadena Anesthesia and Perioperative Medicine. Trauma and Major Surgery Division. Fundación Valle del Lili. Universidad ICESI, Universidad del Valle. Cali, Colombia. https://orcid.org/0000-0001-5012-5125
Keywords: Coagulation disorders, Hemorrhage, Acidosis, Hypothermia, Calcium, Hyperglycemia, Anesthesiology

Abstract

The deadly triad concept represented a dogma in the definition of poor outcomes and death associated with major bleeding in trauma. This model of end-stage disease was then rapidly transferred to other major bleeding scenarios. However, and notwithstanding the fact that it represented a severe scenario, the original triad fails to establish a sequence, which would be relevant when defining the objectives during the initial treatment of severe bleeding.  It has been recently suggested that hypoxia and hyperglycemia should be included as isolated, determining factors in this model. Likewise, the model admits only one scenario where all the conditions shall co-exist, knowing that each one of them contributes with a different risk burden. Based on a structured review, we submit a pentad model that includes a natural pattern of events occurring with hypoxemia as the main trigger for the development of hypocalcemia, hyperglycemia, acidosis and hypothermia, as hallmarks of multiple system impairment. This severity model of major bleeding ends with coagulopathy as a result of the failure to resolve the rest of the previous components.

References

Mann KG, Brummel K, Butenas S. What is all that thrombin for? Journal of Thrombosis and Haemostasis. 2003;1(7):1504-14. doi: https://doi.org/10.1046/j.1538-7836.2003.00298.x

McMichael M. New models of hemostasis. Topics in Companion Animal Medicine. 2012;27(2):40-5. doi: https://doi.org/10.1053/j.tcam.2012.07.005

Hoffman M, Monroe D. A cell-based model of hemostasis. Thrombosis Haemostasis. 2001;85(06):958-65. doi: https://doi.org/10.1055/s-0037-1615947

Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science. 1964;145(3638):1310-2. doi: https://doi.org/10.1126/science.145.3638.1310

Mikhail J. The trauma triad of death: Hypothermia, acidosis, and coagulopathy. AACN Clinical Issues: Advanced Practice in Acute and Critical Care. 1999;10(1):85-94. doi: https://doi.org/10.1097/00044067-199902000-00008

Endo A, Shiraishi A, Otomo Y, Kushimoto S, Saitoh D, Hayakawa M et al. Development of novel criteria of the "lethal triad" as an indicator of decision making in current trauma care. Critical Care Med. 2016;44(9):e797-803. doi: https://doi.org/10.1097/CCM.0000000000001731

Egea-Guerrero JJ, Freire-Aragón MD, Serrano-Lázaro A, Quintana-Díaz M. Resuscitative goals and new strategies in severe trauma patient resuscitation. Medicina Intensiva. 2014;38(8):502-12. doi: https://doi.org/10.1016/j.medin.2014.06.003

Cannon JW. Hemorrhagic shock. New Eng J Med. 2018;378(4):370-9. doi: https://doi.org/10.1056/NEJMra1705649

Maani C, DeSocio PA, Holcomb JB. Coagulopathy in trauma patients: what are the main influence factors? Current Opin Anaesthesiol. 2009;22(2):255-60. doi: https://doi.org/10.1097/ACO.0b013e32832922be

Martini WZ, Holcomb JB. Acidosis and coagulopathy. Ann Surg. 2007;246(5):831-5. doi: https://doi.org/10.1097/SLA.0b013e3180cc2e94

Gore DC, Chinkes D, Heggers J, Herndon DN, Wolf SE, Desai M. Association of hyperglycemia with increased mortality after severe burn injury. J Trauma Acute Care Surg. 2001;51(3):540-4. doi: https://doi.org/10.1097/00005373-200109000-00021

Kassum DA, Thomas EJ, Wong CJ. Early determinants of outcome in blunt injury. Canadian J Surg. 1984;27(1):64-9.

Weissman C. The metabolic response to stress. Anesthesiology. 1990;73(2):308-27. doi: https://doi.org/10.1097/00000542-199008000-00020

Adams JM, Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science. 1998;281(5381):1322-6. doi: https://doi.org/10.1126/science.281.5381.1322

Du XL, Sui GZ, Stockklauser-Färber K, Weiß J, Zink S, Schwippert B, et al. Induction of apoptosis by high proinsulin and glucose in cultured human umbilical vein endothelial cells is mediated by reactive oxygen species. Diabetología. 1998;41(3):249-56. doi: https://doi.org/10.1007/s001250050900

Sung J, Bochicchio G, Joshi M, Bochicchio K, Tracy K, Scalea TM. Admission hyperglycemia is predictive of outcome in critically Ill trauma patients. J Trauma. 2005;59(1):80-3. doi: https://doi.org/10.1097/01.TA.0000171452.96585.84

Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia as a prognostic indicator in trauma. J Trauma. 2003;55(1):33-8. doi: https://doi.org/10.1097/01.TA.0000074434.39928.72

Alexiou GA, Lianos G, Fotakopoulos G, Michos E, Pachatouridis D, Voulgaris S. Admission glucose and coagulopathy occurrence in patients with traumatic brain injury. Brain Injury. 2014;28(4):438-41. doi: https://doi.org/10.3109/02699052.2014.888769

Aljada A, Ghanim H, Mohanty P, Syed T, Bandyopadhyay A, Dandona P. Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations. American J Clin Nutrit. 2004;80(1):51-7. doi: https://doi.org/10.1093/ajcn/80.1.51

Dalainas I. Pathogenesis, diagnosis, and management of disseminated intravascular coagulation: A literature review. Vol. 12. European Review for Medical and Pharmacological Sciences; 2008. p. 19-31.

Bardes JM, Inaba K, Schellenberg M, Grabo D, Strumwasser A, Matsushima K, et al. The contemporary timing of trauma deaths. J Trauma Acute Care Surg. 2018;84(6):893-9. doi: https://doi.org/10.1097/TA.0000000000001882

Moore HB, Moore EE, González E, Chapman MP, Chin TL, Silliman CC, et al. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown. J Trauma Acute Care Surg. 2014;77(6):811-7. doi: https://doi.org/10.1097/TA.0000000000000341

Moore HB, Moore EE, Liras IN, Gonzalez E, Harvin JA, Holcomb JB, et al. Acute fibrinolysis shutdown after injury occurs frequently and increases mortality: A multicenter evaluation of 2,540 severely injured patients. J American College Surg. 2016;222(4):347-55. doi: https://doi.org/10.1016/j.jamcollsurg.2016.01.006

Olldashi F, Kerçi M, Zhurda T, Ruçi K, Banushi A, Traverso MS, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. The Lancet. 2011r;377(9771):1096-1101.e2. doi: https://doi.org/10.1016/S0140-6736(11)60278-X

Morrison JJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113. doi: https://doi.org/10.1001/archsurg.2011.287

Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, et al. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003;31(10):2450-5. doi: https://doi.org/10.1097/01.CCM.0000084871.76568.E6

Vivien B, Langeron O, Morell E, Devilliers C, Carli PA, Coriat P, et al. Early hypocalcemia in severe trauma. Crit Care Med. 2005;33(9):1946-52. doi: https://doi.org/10.1097/01.CCM.0000171840.01892.36

Barry G. Plasma calcium concentration changes in hemorrhagic shock. Am J Physiology-Legacy Content. 1971;220(4):874-9. doi: https://doi.org/10.1152/ajplegacy.1971.220.4.874

Young CC, Seong YH. The value of initial ionized calcium as a predictor of mortality and triage tool in adult trauma patients. J Korean Med Sci. 2008;23(4):700-5. doi: https://doi.org/10.3346/jkms.2008.23.4.700

Zhang Z, Xu X, Ni H, Deng H. Predictive value of ionized calcium in critically Ill patients: An analysis of a large clinical database MIMIC II. PLoS ONE. 2014;9(4):e95204. doi: https://doi.org/10.1371/journal.pone.0095204

Magnotti LJ, Bradburn EH, Webb DL, Berry SD, Fischer PE, Zarzaur BL, et al. Admission ionized calcium levels predict the need for multiple transfusions: A prospective study of 591 critically Ill trauma patients. J Trauma. 2011;70(2):391-7. doi: https://doi.org/10.1097/TA.0b013e31820b5d98

Vasudeva M, Mathew JK, Groombridge C, Tee JW, Johnny CS, Maini A, et al. Hypocalcemia in trauma patients: A systematic review. J Trauma Acute Care Surg. 2021;90(2):396-402. doi: https://doi.org/10.1097/TA.0000000000003027

Ganter MT, Pittet J. New insights into acute coagulopathy in trauma patients. Best Pract Res Clin Anaesthesiol. 2010;24(1):15-25. doi: https://doi.org/10.1016/j.bpa.2009.09.010

Shafi S, Elliott AC, Gentilello L. Is hypothermia simply a marker of shock and injury severity or an independent risk factor for mortality in trauma patients? Analysis of a large national trauma registry. J Trauma. 2005;59(5):1081-5. doi: https://doi.org/10.1097/01.ta.0000188647.03665.fd

Wang HE, Callaway CW, Peitzman AB, Tisherman SA. Admission hypothermia and outcome after major trauma. Critical Care Med. 2005;33(6):1296-301. doi: https://doi.org/10.1097/01.CCM.0000165965.31895.80

Lapostolle F, Sebbah J, Couvreur J, Koch F, Savary D, Tazarourte K, et al. Risk factors for onset of hypothermia in trauma victims: The HypoTraum study. Crit Care. 2012;16(4):R142. doi: https://doi.org/10.1186/cc11449

Jurkovich GJ, et al. Hypothermia in trauma victims. J Trauma. 1987;27(9):1019-24. doi: https://doi.org/10.1097/00005373-198709000-00011

Brohi K, Eaglestone S. Traumatic coagulopathy and massive transfusion: improving outcomes and saving blood. Programme Grants for Applied Research. 2017;5(19):1-74. doi: https://doi.org/10.3310/pgfar05190

Simmons JW, Powell MF. Acute traumatic coagulopathy: pathophysiology and resuscitation. Br J Anaesthesia. 2016;117:iii31-43. doi: https://doi.org/10.1093/bja/aew328

Elmer J, Wilcox SR, Raja AS. Massive transfusion in traumatic shock. J Emerg Med. 2013;44(4):829-38. doi: https://doi.org/10.1016/j.jemermed.2012.11.025

Nardi G, Agostini V, Rondinelli B, Russo E, Bastianini B, Bini G, et al. Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs. Crit Care. 2015;19(1):83. doi: https://doi.org/10.1186/s13054-015-0817-9

Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial. JAMA. 2015;313(5):471-82. doi: https://doi.org/10.1001/jama.2015.12

Godier A, Greinacher A, Faraoni D, Levy JH, Samama CM. Use of factor concentrates for the management of perioperative bleeding: guidance from the SSC of the ISTH. J Thrombosis Haemostasis. 2018;16(1):170-4. doi: https://doi.org/10.1111/jth.13893

González E, Moore EE, Moore HB, Chapman MP, Chin TL, Ghasabyan A, et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy. Ann Surg. 2016;263(6):1051-9. doi: https://doi.org/10.1097/SLA.0000000000001608

da Luz LT, Nascimento B, Shankarakutty AK, Rizoli S, Adhikari NK. Effect of thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review. Crit Care. 2014;18(5):518. doi: https://doi.org/10.1186/s13054-014-0518-9

How to Cite
1.
Quintana-Díaz M, Garay-Fernández M, Ariza-Cadena F. Advancing in the understanding of coagulopathy during hemorrhagic shock: From the triad to the deadly pentad. Colomb. J. Anesthesiol. [Internet]. 2022 May 13 [cited 2022 Dec. 2];50(4). Available from: https://www.revcolanest.com.co/index.php/rca/article/view/1038

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Published
2022-05-13
How to Cite
1.
Quintana-Díaz M, Garay-Fernández M, Ariza-Cadena F. Advancing in the understanding of coagulopathy during hemorrhagic shock: From the triad to the deadly pentad. Colomb. J. Anesthesiol. [Internet]. 2022 May 13 [cited 2022 Dec. 2];50(4). Available from: https://www.revcolanest.com.co/index.php/rca/article/view/1038
Section
Narrative review
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