Review Article| Volume 41, ISSUE 1, P51-69, February 2023

Massive Hemorrhage Protocol

A Practical Approach to the Bleeding Trauma Patient


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Emergency Medicine Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Cannon J.W.
        • Khan M.A.
        • Raja A.S.
        • et al.
        Damage control resuscitation in patients with severe traumatic hemorrhage: A practice management guideline from the Eastern Association for the Surgery of Trauma.
        J Trauma Acute Care Surg. 2017; 82: 605-617
        • Cotton B.A.
        • Dossett L.A.
        • Au B.K.
        • et al.
        Room for (performance) improvement: provider-related factors associated with poor outcomes in massive transfusion.
        J Trauma. 2009; 67: 1004-1012
        • Khan S.
        • Allard S.
        • Weaver A.
        • et al.
        A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion.
        Injury. 2013; 44: 587-592
        • Milligan C.
        • Higginson I.
        • Smith J.E.
        Emergency department staff knowledge of massive transfusion for trauma: the need for an evidence based protocol.
        Emerg Med J. 2011; 28: 870-872
        • Nunez T.C.
        • Young P.P.
        • Holcomb J.B.
        • et al.
        Creation, implementation, and maturation of a massive transfusion protocol for the exsanguinating trauma patient.
        J Trauma. 2010; 68: 1498-1505
        • Lim G.
        • Harper-Kirksey K.
        • Parekh R.
        • et al.
        Efficacy of a massive transfusion protocol for hemorrhagic trauma resuscitation.
        Am J Emerg Med. 2018; 36: 1178-1181
        • Callum J.L.
        • Yeh C.H.
        • Petrosoniak A.
        • et al.
        A regional massive hemorrhage protocol developed through a modified Delphi technique.
        CMAJ Open. 2019; 7: E546-E561
        • Narayan S.E.
        • Poles D.
        • eaobotSHoTSS Group
        The 2020 Annual SHOT Report. Serious Hazards of Transfusion (SHOT) 2021.
        (Available at:) (Accessed April 1, 2022)
        • Meyer D.E.
        • Vincent L.E.
        • Fox E.E.
        • et al.
        Every minute counts: Time to delivery of initial massive transfusion cooler and its impact on mortality.
        J Trauma Acute Care Surg. 2017; 83: 19-24
        • Pham H.P.
        • Shaz B.H.
        Update on massive transfusion.
        Br J Anaesth. 2013; 111: i71-i82
        • Brockamp T.
        • Nienaber U.
        • Mutschler M.
        • et al.
        Predicting on-going hemorrhage and transfusion requirement after severe trauma: a validation of six scoring systems and algorithms on the TraumaRegister DGU.
        Crit Care. 2012; 16: R129
        • Cotton B.A.
        • Dossett L.A.
        • Haut E.R.
        • et al.
        Multicenter validation of a simplified score to predict massive transfusion in trauma.
        J Trauma. 2010; 69: S33-S39
        • Nunez T.C.
        • Voskresensky I.V.
        • Dossett L.A.
        • et al.
        Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)?.
        J Trauma. 2009; 66: 346-352
        • Schroll R.
        • Swift D.
        • Tatum D.
        • et al.
        Accuracy of shock index versus ABC score to predict need for massive transfusion in trauma patients.
        Injury. 2018; 49: 15-19
        • Hanna K.
        • Harris C.
        • Trust M.D.
        • et al.
        Multicenter Validation of the Revised Assessment of Bleeding and Transfusion (RABT) Score for Predicting Massive Transfusion.
        World J Surg. 2020; 44: 1807-1816
        • Meyer D.E.
        • Cotton B.A.
        • Fox E.E.
        • et al.
        A comparison of resuscitation intensity and critical administration threshold in predicting early mortality among bleeding patients: A multicenter validation in 680 major transfusion patients.
        J Trauma Acute Care Surg. 2018; 85: 691-696
        • Warren J.
        • Moazzez A.
        • Chong V.
        • et al.
        Narrowed pulse pressure predicts massive transfusion and emergent operative intervention following penetrating trauma.
        Am J Surg. 2019; 218: 1185-1188
        • Savage S.A.
        • Sumislawski J.J.
        • Zarzaur B.L.
        • et al.
        The new metric to define large-volume hemorrhage: results of a prospective study of the critical administration threshold.
        J Trauma Acute Care Surg. 2015; 78 ([discussion: 229–30]): 224-229
        • Damme C.D.
        • Luo J.
        • Buesing K.L.
        Isolated prehospital hypotension correlates with injury severity and outcomes in patients with trauma.
        Trauma Surg Acute Care Open. 2016; 1: e000013
        • Kheirbek T.
        • Martin T.J.
        • Cao J.
        • et al.
        Prehospital shock index outperforms hypotension alone in predicting significant injury in trauma patients.
        Trauma Surg Acute Care Open. 2021; 6: e000712
        • Ohmori T.
        • Kitamura T.
        • Tanaka K.
        • et al.
        Bleeding sites in elderly trauma patients who required massive transfusion: a comparison with younger patients.
        Am J Emerg Med. 2016; 34: 123-127
        • Martinetti A.
        • Awadhpersad P.
        • Singh S.
        • et al.
        Gone in 2s: a deep dive into perfection analysing the collaborative maintenance pitstop of Formula 1.
        J Qual Maintenance Eng. 2021; 27: 550-564
        • Bogdanovic J.
        • Perry J.
        • Guggenheim M.
        • et al.
        Adaptive coordination in surgical teams: an interview study.
        BMC Health Serv Res. 2015; 15: 128
        • Hicks C.
        • Petrosoniak A.
        The Human Factor: Optimizing Trauma Team Performance in Dynamic Clinical Environments.
        Emerg Med Clin North Am. 2018; 36: 1-17
        • Mathieu J.
        • Goodwin G.
        • Heffner T.
        • et al.
        The Influence of Shared Mental Models on Team Process and Performance.
        Joural Appl Psychol. 2000; 85: 273-283
        • Westli H.K.
        • Johnsen B.H.
        • Eid J.
        • et al.
        Teamwork skills, shared mental models, and performance in simulated trauma teams: an independent group design.
        Scand J Trauma Resuscitation Emerg Med. 2010; 18: 47
        • Baksaas-Aasen K.
        • Gall L.S.
        • Stensballe J.
        • et al.
        Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.
        Intensive Care Med. 2021; 47: 49-59
        • collaborators C-t
        • Shakur H.
        • Roberts I.
        • et al.
        Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.
        Lancet. 2010; 376: 23-32
        • Guyette F.X.
        • Brown J.B.
        • Zenati M.S.
        • et al.
        Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury: A Double-blind, Placebo-Controlled, Randomized Clinical Trial.
        JAMA Surg. 2020; 156: 11-20
        • Rowell S.E.
        • Meier E.N.
        • McKnight B.
        • et al.
        Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.
        JAMA. 2020; 324: 961-974
        • collaborators C-t
        Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.
        Lancet. 2019; 394: 1713-1723
        • Collaborators W.T.
        Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.
        Lancet. 2017; 389: 2105-2116
        • Gayet-Ageron A.
        • Prieto-Merino D.
        • Ker K.
        • et al.
        Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients.
        Lancet. 2018; 391: 125-132
        • Ageron F.X.
        • Coats T.J.
        • Darioli V.
        • et al.
        Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: usefulness for tranexamic acid treatment criteria.
        Scand J Trauma Resusc Emerg Med. 2021; 29: 6
        • Morrison J.J.
        • Dubose J.J.
        • Rasmussen T.E.
        • et al.
        Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study.
        Arch Surg. 2012; 147: 113-119
        • Kane Z.
        • Picetti R.
        • Wilby A.
        • et al.
        Physiologically based modelling of tranexamic acid pharmacokinetics following intravenous, intramuscular, sub-cutaneous and oral administration in healthy volunteers.
        Eur J Pharm Sci. 2021; 164: 105893
        • Collaborators H.-I.T.
        Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial.
        Lancet. 2020; 395: 1927-1936
        • Dixon A.L.
        • McCully B.H.
        • Rick E.A.
        • et al.
        Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.
        J Trauma Acute Care Surg. 2020; 89: 900-907
        • Moore E.E.
        • Moore H.B.
        • Gonzalez E.
        • et al.
        Rationale for the selective administration of tranexamic acid to inhibit fibrinolysis in the severely injured patient.
        Transfusion. 2016; 56: S110-S114
        • David J.S.
        • Lambert A.
        • Bouzat P.
        • et al.
        Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality: A retrospective analysis.
        Eur J Anaesthesiol. 2020; 37: 170-179
        • Gomez-Builes J.C.
        • Acuna S.A.
        • Nascimento B.
        • et al.
        Harmful or Physiologic: Diagnosing Fibrinolysis Shutdown in a Trauma Cohort With Rotational Thromboelastometry.
        Anesth Analg. 2018; 127: 840-849
        • Stein P.
        • Studt J.D.
        • Albrecht R.
        • et al.
        The Impact of Prehospital Tranexamic Acid on Blood Coagulation in Trauma Patients.
        Anesth Analg. 2018; 126: 522-529
        • Guerriero C.
        • Cairns J.
        • Perel P.
        • et al.
        Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial.
        PLoS One. 2011; 6: e18987
        • Al-Jeabory M.
        • Szarpak L.
        • Attila K.
        • et al.
        Efficacy and Safety of Tranexamic Acid in Emergency Trauma: A Systematic Review and Meta-Analysis.
        J Clin Med. 2021; 3: 10
        • Lester E.L.W.
        • Fox E.E.
        • Holcomb J.B.
        • et al.
        The impact of hypothermia on outcomes in massively transfused patients.
        J Trauma Acute Care Surg. 2019; 86: 458-463
        • Rajagopalan S.
        • Mascha E.
        • Na J.
        • et al.
        The effects of mild perioperative hypothermia on blood loss and transfusion requirement.
        Anesthesiology. 2008; 108: 71-77
        • Poder T.G.
        • Pruneau D.
        • Dorval J.
        • et al.
        Effect of warming and flow rate conditions of blood warmers on red blood cell integrity.
        Vox Sang. 2016; 111: 341-349
        • Marik P.E.
        Obituary: pulmonary artery catheter 1970 to 2013.
        Ann Intensive Care. 2013; 3: 38
        • Perlman R.
        • Callum J.
        • Laflamme C.
        • et al.
        A recommended early goal-directed management guideline for the prevention of hypothermia-related transfusion, morbidity, and mortality in severely injured trauma patients.
        Crit Care. 2016; 20: 107
        • Barnett B.J.
        • Nunberg S.
        • Tai J.
        • et al.
        Oral and tympanic membrane temperatures are inaccurate to identify Fever in emergency department adults.
        West J Emerg Med. 2011; 12: 505-511
        • Niven D.J.
        • Gaudet J.E.
        • Laupland K.B.
        • et al.
        Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis.
        Ann Intern Med. 2015; 163: 768-777
        • O'Grady N.P.
        • Barie P.S.
        • Bartlett J.G.
        • et al.
        Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America.
        Crit Care Med. 2008; 36: 1330-1349
        • Soar J.
        • Perkins G.D.
        • Abbas G.
        • et al.
        European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution.
        Resuscitation. 2010; 81: 1400-1433
        • Asadian S.
        • Khatony A.
        • Moradi G.
        • et al.
        Accuracy and precision of four common peripheral temperature measurement methods in intensive care patients.
        Med Devices (Auckl). 2016; 9: 301-308
        • Uleberg O.
        • Eidstuen S.C.
        • Vangberg G.
        • et al.
        Temperature measurements in trauma patients: is the ear the key to the core?.
        Scand J Trauma Resusc Emerg Med. 2015; 23: 101
        • Tsuei B.J.
        • Kearney P.A.
        Hypothermia in the trauma patient.
        Injury. 2004; 35: 7-15
        • Brauer A.
        • Quintel M.
        Forced-air warming: technology, physical background and practical aspects.
        Curr Opin Anaesthesiol. 2009; 22: 769-774
        • Kober A.
        • Scheck T.
        • Fulesdi B.
        • et al.
        Effectiveness of resistive heating compared with passive warming in treating hypothermia associated with minor trauma: a randomized trial.
        Mayo Clin Proc. 2001; 76: 369-375
        • Lundgren P.
        • Henriksson O.
        • Naredi P.
        • et al.
        The effect of active warming in prehospital trauma care during road and air ambulance transportation - a clinical randomized trial.
        Scand J Trauma Resusc Emerg Med. 2011; 19: 59
        • Poder T.G.
        • Nonkani W.G.
        • Tsakeu Leponkouo E.
        Blood Warming and Hemolysis: A Systematic Review With Meta-Analysis.
        Transfus Med Rev. 2015; 29: 172-180
        • Alam A.
        • Olarte R.
        • Callum J.
        • et al.
        Hypothermia indices among severely injured trauma patients undergoing urgent surgery: A single-centred retrospective quality review and analysis.
        Injury. 2018; 49: 117-123
        • Sedlak S.K.
        Hypothermia in trauma: the nurse's role in recognition, prevention, and management.
        Int J Trauma Nurs. 1995; 1: 19-26
        • Lawson L.L.
        Hypothermia and trauma injury: temperature monitoring and rewarming strategies.
        Crit Care Nurs Q. 1992; 15: 21-32
        • Meneses E.
        • Boneva D.
        • McKenney M.
        • et al.
        Massive transfusion protocol in adult trauma population.
        Am J Emerg Med. 2020; 38: 2661-2666
        • Holcomb J.B.
        • Tilley B.C.
        • Baraniuk S.
        • 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: 471-482
        • Vlaar A.P.J.
        • Dionne J.C.
        • de Bruin S.
        • et al.
        Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine.
        Intensive Care Med. 2021; 47: 1368-1392
        • Caspers M.
        • Maegele M.
        • Frohlich M.
        Current strategies for hemostatic control in acute trauma hemorrhage and trauma-induced coagulopathy.
        Expert Rev Hematol. 2018; 11: 987-995
        • Harker L.A.
        • Slichter S.J.
        The bleeding time as a screening test for evaluation of platelet function.
        N Engl J Med. 1972; 287: 155-159
        • Anderson T.N.
        • Schreiber M.A.
        • Rowell S.E.
        Viscoelastic Testing in Traumatic Brain Injury: Key Research Insights.
        Transfus Med Rev. 2021; 35: 108-112
        • Da Luz L.T.
        • Nascimento B.
        • Shankarakutty A.K.
        • et al.
        Effect of thromboelastography (TEG(R)) and rotational thromboelastometry (ROTEM(R)) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review.
        Crit Care. 2014; 18: 518
        • Brill J.B.
        • Brenner M.
        • Duchesne J.
        • et al.
        The Role of TEG and ROTEM in Damage Control Resuscitation.
        Shock. 2021; 56: 52-61
        • Frith D.
        • Davenport R.
        • Brohi K.
        Acute traumatic coagulopathy.
        Curr Opin Anaesthesiol. 2012; 25: 229-234
        • Abdel-Wahab O.I.
        • Healy B.
        • Dzik W.H.
        Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities.
        Transfusion (Paris). 2006; 46: 1279-1285
        • Holland L.L.
        • Brooks J.P.
        Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results.
        Am J Clin Pathol. 2006; 126: 133-139
        • Kao T.W.
        • Lee Y.C.
        • Chang H.T.
        Prothrombin Complex Concentrate for Trauma Induced Coagulopathy: A Systematic Review and Meta-Analysis.
        J Acute Med. 2021; 11: 81-89
        • van den Brink D.P.
        • Wirtz M.R.
        • Neto A.S.
        • et al.
        Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta-analysis.
        J Thromb Haemost. 2020; 18: 2457-2467
        • Karkouti K.
        • Bartoszko J.
        • Grewal D.
        • et al.
        Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial.
        JAMA Netw Open. 2021; 4: e213936
        • Baharoglu M.I.
        • Cordonnier C.
        • Al-Shahi Salman R.
        • et al.
        Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.
        Lancet. 2016; 387: 2605-2613
        • Godier A.
        • Garrigue D.
        • Lasne D.
        • et al.
        Management of antiplatelet therapy for non-elective invasive procedures or bleeding complications: Proposals from the French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Thrombosis and Haemostasis (GFHT), in collaboration with the French Society for Anaesthesia and Intensive Care (SFAR).
        Arch Cardiovasc Dis. 2019; 112: 199-216
        • Yorkgitis B.K.
        • Tatum D.M.
        • Taghavi S.
        • et al.
        Eastern Association for the Surgery of Trauma Multicenter Trial: Comparison of pre-injury antithrombotic use and reversal strategies among severe traumatic brain injury patients.
        J Trauma Acute Care Surg. 2022; 92: 88-92
        • Hayakawa M.
        • Gando S.
        • Ono Y.
        • et al.
        Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study.
        Semin Thromb Hemost. 2015; 41: 35-42
        • Bouzat P.
        • Ageron F.X.
        • Charbit J.
        • et al.
        Modelling the association between fibrinogen concentration on admission and mortality in patients with massive transfusion after severe trauma: an analysis of a large regional database.
        Scand J Trauma Resusc Emerg Med. 2018; 26: 55
        • Levy J.H.
        • Welsby I.
        • Goodnough L.T.
        Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy.
        Transfusion (Paris). 2014; 54 ([quiz: 1388]): 1389-1405
        • Foster J.C.
        • Sappenfield J.W.
        • Smith R.S.
        • et al.
        Initiation and Termination of Massive Transfusion Protocols: Current Strategies and Future Prospects.
        Anesth Analg. 2017; 125: 2045-2055
        • Margarido C.
        • Ferns J.
        • Chin V.
        • et al.
        Massive hemorrhage protocol activation in obstetrics: a 5-year quality performance review.
        Int J Obstet Anesth. 2019; 38: 37-45