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Semin Thromb Hemost 2020; 46(01): 073-082
DOI: 10.1055/s-0039-1697932
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Surgery in Traumatic Injury and Perioperative Considerations

Nicola Curry
1   Department of Clinical Haematology, Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, United Kingdom
2   NIHR Oxford Biomedical Research Centre, Blood Theme, Oxford Centre for Haematology, Oxford University, Oxford, United Kingdom
,
Karim Brohi
3   Centre for Trauma Sciences, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
28 September 2019 (online)

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Abstract

A severely injured patient presents several unique challenges to an admitting trauma team. Not only must the extent of the patient's injuries, particularly those that are life-threatening, be determined within minutes of hospital arrival, but also the trauma team needs to be able to assess whether the patient is bleeding and/or has an attendant coagulopathy. Early management of trauma patients is dictated by the presence (or absence) of significant bleeding. Standard definitive surgical procedures can be conducted in hemodynamically stable patients, but those in hemorrhagic shock should be treated according to damage control resuscitation (DCR) principles. DCR is a practice that has evolved over the last two to three decades, combining limited surgical techniques, which provide early hemorrhage control, and balanced transfusion resuscitation strategies, which mitigate (and ideally) treat trauma-induced coagulopathy (TIC). This review describes the contemporary perioperative management of trauma patients who have significant bleeding and/or TIC and sets out the evidence around the current approach for hemostatic resuscitation in these patients.

Keywords

damage control - hemostatic resuscitation - trauma-induced coagulopathy - perioperative management
 

  • References

  • 1 Curry N, Hopewell S, Dorée C, Hyde C, Brohi K, Stanworth S. The acute management of trauma hemorrhage: a systematic review of randomized controlled trials. Crit Care 2011; 15 (02) R92
    CrossrefPubMedGoogle Scholar
  • 2 National Institute of Health and Clinical Excellence. Major trauma: assessment and initial management. NICE guidance [NG39]. (2016) Available at: https://www.nice.org.uk/guidance/ng39 . Accessed February 12, 2019
    PubMedGoogle Scholar
  • 3 Holcomb JB, del Junco DJ, Fox EE. , et al; PROMMTT Study Group. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg 2013; 148 (02) 127-136
    CrossrefPubMedGoogle Scholar
  • 4 Lamb CM, MacGoey P, Navarro AP, Brooks AJ. Damage control surgery in the era of damage control resuscitation. Br J Anaesth 2014; 113 (02) 242-249
    CrossrefPubMedGoogle Scholar
  • 5 Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003; 54 (06) 1127-1130
    CrossrefPubMedGoogle Scholar
  • 6 Zakrison TL, Leung E, McCredie V. , et al. Canadian traumatologists and the recognition of occult shock: results of a national survey. PAJT 2013; 2: 33-36
    PubMedGoogle Scholar
  • 7 Wo CC, Shoemaker WC, Appel PL, Bishop MH, Kram HB, Hardin E. Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness. Crit Care Med 1993; 21 (02) 218-223
    CrossrefPubMedGoogle Scholar
  • 8 American College of Surgeons Committee on Trauma. Advanced Trauma Life Support for Doctors: Student Course Manual. Chicago, IL: American College of Surgeons; 2008
    Google Scholar
  • 9 Eastridge BJ, Salinas J, McManus JG. , et al. Hypotension begins at 110 mm Hg: redefining “hypotension” with data. J Trauma 2007; 63 (02) 291-297 , discussion 297–299
    CrossrefPubMedGoogle Scholar
  • 10 Hasler RM, Nuesch E, Jüni P, Bouamra O, Exadaktylos AK, Lecky F. Systolic blood pressure below 110 mm Hg is associated with increased mortality in blunt major trauma patients: multicentre cohort study. Resuscitation 2011; 82 (09) 1202-1207
    CrossrefPubMedGoogle Scholar
  • 11 Guly HR, Bouamra O, Spiers M, Dark P, Coats T, Lecky FE. ; Trauma Audit and Research Network. Vital signs and estimated blood loss in patients with major trauma: testing the validity of the ATLS classification of hypovolaemic shock. Resuscitation 2011; 82 (05) 556-559
    CrossrefPubMedGoogle Scholar
  • 12 Rossaint R, Bouillon B, Cerny V. , et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care 2016; 20: 100
    CrossrefPubMedGoogle Scholar
  • 13 Tonglet ML. Early prediction of ongoing hemorrhage in severe trauma: presentation of the existing scoring systems. Arch Trauma Res 2016; 5 (04) e33377
    PubMedGoogle Scholar
  • 14 Yücel N, Lefering R, Maegele M. , et al; Polytrauma Study Group of the German Trauma Society. Trauma Associated Severe Hemorrhage (TASH)-Score: probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma. J Trauma 2006; 60 (06) 1228-1236 , discussion 1236–1237
    CrossrefPubMedGoogle Scholar
  • 15 Nunez TC, Voskresensky IV, Dossett LA, Shinall R, Dutton WD, Cotton BA. Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)?. J Trauma 2009; 66 (02) 346-352
    CrossrefPubMedGoogle Scholar
  • 16 Cantle PM, Cotton BA. Prediction of massive transfusion in trauma. Crit Care Clin 2017; 33 (01) 71-84
    CrossrefPubMedGoogle Scholar
  • 17 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 (01) 15-19
    CrossrefPubMedGoogle Scholar
  • 18 Cotton BA, Reddy N, Hatch QM. , et al. Damage control resuscitation is associated with a reduction in resuscitation volumes and improvement in survival in 390 damage control laparotomy patients. Ann Surg 2011; 254 (04) 598-605
    CrossrefPubMedGoogle Scholar
  • 19 Naumann DN, Khan MA, Smith JE, Rickard R, Woolley T. Future strategies for remote damage control resuscitation after traumatic hemorrhage. J Trauma Acute Care Surg 2019; 86 (01) 163-166
    CrossrefPubMedGoogle Scholar
  • 20 Pohlman TH, Fecher AM, Arreola-Garcia C. Optimizing transfusion strategies in damage control resuscitation: current insights. J Blood Med 2018; 9: 117-133
    CrossrefPubMedGoogle Scholar
  • 21 Bickell WH, Wall Jr MJ, Pepe PE. , et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994; 331 (17) 1105-1109
    CrossrefPubMedGoogle Scholar
  • 22 Dutton RP. Low-pressure resuscitation from hemorrhagic shock. Int Anesthesiol Clin 2002; 40 (03) 19-30
    CrossrefPubMedGoogle Scholar
  • 23 Cap AP, Pidcoke HF, Spinella P. , et al. Damage control resuscitation. Mil Med 2018; 183 (Suppl. 02) 36-43
    CrossrefPubMedGoogle Scholar
  • 24 Rotondo MF, Schwab CW, McGonigal MD. , et al. ‘Damage control’: an approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma 1993; 35 (03) 375-382 , discussion 382–383
    CrossrefPubMedGoogle Scholar
  • 25 Wang CH, Hsieh WH, Chou HC. , et al. Liberal versus restricted fluid resuscitation strategies in trauma patients: a systematic review and meta-analysis of randomized controlled trials and observational studies. Crit Care Med 2014; 42 (04) 954-961
    CrossrefPubMedGoogle Scholar
  • 26 Holcomb JB, Jenkins D, Rhee P. , et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma 2007; 62 (02) 307-310
    CrossrefPubMedGoogle Scholar
  • 27 Davenport RA, Guerreiro M, Frith D. , et al. Activated protein C drives the hyperfibrinolysis of acute traumatic coagulopathy. Anesthesiology 2017; 126 (01) 115-127
    CrossrefPubMedGoogle Scholar
  • 28 Cohen MJ, Kutcher M, Redick B. , et al; PROMMTT Study Group. Clinical and mechanistic drivers of acute traumatic coagulopathy. J Trauma Acute Care Surg 2013; 75 (01) (Suppl. 01) S40-S47
    CrossrefPubMedGoogle Scholar
  • 29 Frith D, Goslings JC, Gaarder C. , et al. Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations. J Thromb Haemost 2010; 8 (09) 1919-1925
    CrossrefPubMedGoogle Scholar
  • 30 Dunbar NM, Chandler WL. Thrombin generation in trauma patients. Transfusion 2009; 49 (12) 2652-2660
    CrossrefPubMedGoogle Scholar
  • 31 Cardenas JC, Rahbar E, Pommerening MJ. , et al. Measuring thrombin generation as a tool for predicting hemostatic potential and transfusion requirements following trauma. J Trauma Acute Care Surg 2014; 77 (06) 839-845
    CrossrefPubMedGoogle Scholar
  • 32 Chapman MP, Moore EE, Moore HB. , et al. Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients. J Trauma Acute Care Surg 2016; 80 (01) 16-23 , discussion 23–25
    CrossrefPubMedGoogle Scholar
  • 33 Esmon CT. The protein C pathway. Chest 2003; 124 (3, Suppl): 26S-32S
    CrossrefPubMedGoogle Scholar
  • 34 Brohi K, Cohen MJ, Ganter MT. , et al. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma 2008; 64 (05) 1211-1217 , discussion 1217
    CrossrefPubMedGoogle Scholar
  • 35 Raza I, Davenport R, Rourke C. , et al. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost 2013; 11 (02) 307-314
    CrossrefPubMedGoogle Scholar
  • 36 Simmons JW, Powell MF. Acute traumatic coagulopathy: pathophysiology and resuscitation. Br J Anaesth 2016; 117 (Suppl. 03) iii31-iii43
    CrossrefPubMedGoogle Scholar
  • 37 Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg 2011; 254 (02) 194-200
    CrossrefPubMedGoogle Scholar
  • 38 Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg 2012; 73 (01) 60-66
    CrossrefPubMedGoogle Scholar
  • 39 Solomon C, Traintinger S, Ziegler B. , et al. Platelet function following trauma. A multiple electrode aggregometry study. Thromb Haemost 2011; 106 (02) 322-330
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Kutcher ME, Redick BJ, McCreery RC. , et al. Characterization of platelet dysfunction after trauma. J Trauma Acute Care Surg 2012; 73 (01) 13-19
    CrossrefPubMedGoogle Scholar
  • 41 Vulliamy P, Gillespie S, Gall LS, Green L, Brohi K, Davenport RA. Platelet transfusions reduce fibrinolysis but do not restore platelet function during trauma hemorrhage. J Trauma Acute Care Surg 2017; 83 (03) 388-397
    CrossrefPubMedGoogle Scholar
  • 42 Martini WZ, Chinkes DL, Pusateri AE. , et al. Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs. Am J Physiol Endocrinol Metab 2005; 289 (05) E930-E934
    CrossrefPubMedGoogle Scholar
  • 43 Wolberg AS, Campbell RA. Thrombin generation, fibrin clot formation and hemostasis. Transfus Apheresis Sci 2008; 38 (01) 15-23
    CrossrefPubMedGoogle Scholar
  • 44 Booth C, Allard S. Major haemorrhage protocols. ISBT Sci Ser 2018; 13: 219-228
    CrossrefPubMedGoogle Scholar
  • 45 Dzik WH. Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rep 2004; 3 (05) 324-330
    PubMedGoogle Scholar
  • 46 Young PP, Cotton BA, Goodnough LT. Massive transfusion protocols for patients with substantial hemorrhage. Transfus Med Rev 2011; 25 (04) 293-303
    CrossrefPubMedGoogle Scholar
  • 47 Shakur H, Roberts I, Bautista R. , et al; CRASH-2 trial collaborators. 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 (9734): 23-32
    CrossrefPubMedGoogle Scholar
  • 48 Holcomb JB, Tilley BC, Baraniuk S. , et al; PROPPR Study Group. 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 (05) 471-482
    CrossrefPubMedGoogle Scholar
  • 49 Moore HB, Moore EE, Chapman MP. , et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet 2018; 392 (10144): 283-291
    CrossrefPubMedGoogle Scholar
  • 50 Sperry JL, Guyette FX, Brown JB. , et al; PAMPer Study Group. Prehospital plasma during air medical transport in trauma patients at risk for haemorrhagic shock. N Engl J Med 2018; 379 (04) 315-326
    CrossrefPubMedGoogle Scholar
  • 51 Schafer N, Driessen A, Frohlich M. , et al. ; TACTIC partners. Diversity in clinical management and protocols for the management of major bleeding of trauma patients across European level 1 Trauma Centres. Scand J Trauma Resusc Emerg Med 2015; 23: 74
    CrossrefPubMedGoogle Scholar
  • 52 Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron FX, Roberts I. ; Antifibrinolytic Trials Collaboration. 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 (10116): 125-132
    CrossrefPubMedGoogle Scholar
  • 53 Roberts I, Shakur H, Afolabi A. , et al; CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011; 377 (9771): 1096-1101 , 1101.e1–1101.e2
    CrossrefPubMedGoogle Scholar
  • 54 Lord JM, Midwinter MJ, Chen YF. , et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet 2014; 384 (9952): 1455-1465
    CrossrefPubMedGoogle Scholar
  • 55 Zehtabchi S, Nishijima DK. Impact of transfusion of fresh-frozen plasma and packed red blood cells in a 1:1 ratio on survival of emergency department patients with severe trauma. Acad Emerg Med 2009; 16 (05) 371-378
    CrossrefPubMedGoogle Scholar
  • 56 Murad MH, Stubbs JR, Gandhi MJ. , et al. The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 2010; 50 (06) 1370-1383
    CrossrefPubMedGoogle Scholar
  • 57 Kozar RA, Peng Z, Zhang R. , et al. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg 2011; 112 (06) 1289-1295
    CrossrefPubMedGoogle Scholar
  • 58 Watson JJ, Pati S, Schreiber MA. Plasma transfusion: history, current realities, and novel improvements. Shock 2016; 46 (05) 468-479
    CrossrefPubMedGoogle Scholar
  • 59 Khan S, Davenport R, Raza I. , et al. Damage control resuscitation using blood component therapy in standard doses has a limited effect on coagulopathy during trauma hemorrhage. Intensive Care Med 2015; 41 (02) 239-247
    CrossrefPubMedGoogle Scholar
  • 60 Perkins JG, Cap AP, Spinella PC. , et al. An evaluation of the impact of apheresis platelets used in the setting of massively transfused trauma patients. J Trauma 2009; 66 (4, Suppl): S77-S84 , discussion S84–S85
    CrossrefPubMedGoogle Scholar
  • 61 Inaba K, Lustenberger T, Rhee P. , et al. The impact of platelet transfusion in massively transfused trauma patients. J Am Coll Surg 2010; 211 (05) 573-579
    CrossrefPubMedGoogle Scholar
  • 62 Shaz BH, Dente CJ, Nicholas J. , et al. Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients. Transfusion 2010; 50 (02) 493-500
    CrossrefPubMedGoogle Scholar
  • 63 Hallet J, Lauzier F, Mailloux O. , et al. The use of higher platelet: RBC transfusion ratio in the acute phase of trauma resuscitation: a systematic review. Crit Care Med 2013; 41 (12) 2800-2811
    CrossrefPubMedGoogle Scholar
  • 64 Cotton BA, Gunter OL, Isbell J. , et al. Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma 2008; 64 (05) 1177-1182 , discussion 1182–1183
    CrossrefPubMedGoogle Scholar
  • 65 del Junco DJ, Holcomb JB, Fox EE. , et al; PROMMTT Study Group. Resuscitate early with plasma and platelets or balance blood products gradually: findings from the PROMMTT study. J Trauma Acute Care Surg 2013; 75 (01) (Suppl. 01) S24-S30
    CrossrefPubMedGoogle Scholar
  • 66 Davenport RA, Brohi K. Cause of trauma-induced coagulopathy. Curr Opin Anaesthesiol 2016; 29 (02) 212-219
    CrossrefPubMedGoogle Scholar
  • 67 Curry NS, Davenport R, Pavord S. , et al. The use of viscoelastic haemostatic assays in the management of major bleeding: a British Society for Haematology Guideline. Br J Haematol 2018; 182 (06) 789-806
    CrossrefPubMedGoogle Scholar
  • 68 Whiting P, Al M, Westwood M. , et al. Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: a systematic review and cost-effectiveness analysis. Health Technol Assess 2015; 19 (58) 1-228
    PubMedGoogle Scholar
  • 69 Gonzalez E, Moore EE, Moore HB. , et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg 2016; 263 (06) 1051-1059
    CrossrefPubMedGoogle Scholar
  • 70 Innerhofer P, Fries D, Mittermayr M. , et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol 2017; 4 (06) e258-e271
    CrossrefPubMedGoogle Scholar
  • 71 Bakaas-Aasen K, Van Dieren S, Balvers K. , et al , the TACTIC/INTRN collaborators. Data-driven development of ROTEM and TEG algorithms for the management of trauma hemorrhage. A prospective observational multicenter study. Annals of Surg 2018; (e-pub ahead of print) DOI: 10.1097/sla.0000000000002825.
    CrossrefPubMedGoogle Scholar
  • 72 Wong H, Curry N. Do we need cryoprecipitate in the era of fibrinogen concentrate and other specific factor replacement options?. ISBT Sci Ser 2018; 13: 23-28
    CrossrefPubMedGoogle Scholar
  • 73 Rourke C, Curry N, Khan S. , et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost 2012; 10 (07) 1342-1351
    CrossrefPubMedGoogle Scholar
  • 74 Schöchl H, Cotton B, Inaba K. , et al. FIBTEM provides early prediction of massive transfusion in trauma. Crit Care 2011; 15 (06) R265
    CrossrefPubMedGoogle Scholar
  • 75 Curry N, Rourke C, Davenport R. , et al. Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth 2015; 115 (01) 76-83
    CrossrefPubMedGoogle Scholar
  • 76 Curry N, Foley C, Wong H. , et al. Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial. Crit Care 2018; b 22 (01) 164
    CrossrefPubMedGoogle Scholar
  • 77 Nascimento B, Callum J, Tien H. , et al. Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial. Br J Anaesth 2016; 117 (06) 775-782
    CrossrefPubMedGoogle Scholar
  • 78 Marsden M, Benger J, Brohi K. , et al on behalf of the CRYOSTAT-2 investigators. Coagulopathy, cryoprecipitate and CRYOSTAT-2 realising the potential of a nationwide trauma system for a national clinical trial. Br J Anaesth 2019; 122 (02) 164-169
    CrossrefPubMedGoogle Scholar
  • 79 Adams SD, Holcomb JB. Geriatric trauma. Curr Opin Crit Care 2015; 21 (06) 520-526
    PubMedGoogle Scholar
  • 80 Ruff CT, Giugliano RP, Braunwald E. , et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962
    CrossrefPubMedGoogle Scholar
  • 81 Gómez-Outes A, Terleira-Fernández A-I, Calvo-Rojas G, Suárez-Gea ML, Vargas-Castrillón E. Direct oral anticoagulants for stroke prevention in patients with atrial fibrillation: meta-analysis by geographic region with a focus on European patients. Br J Clin Pharmacol 2016; 82 (03) 633-644
    CrossrefPubMedGoogle Scholar
  • 82 Lecky FE, Omar M, Bouamra O. , et al. The effect of preinjury warfarin use on mortality rates in trauma patients: a European multicentre study. Emerg Med J 2015; 32 (12) 916-920
    CrossrefPubMedGoogle Scholar
  • 83 Oake N, Fergusson DA, Forster AJ, van Walraven C. Frequency of adverse events in patients with poor anticoagulation: a meta-analysis. CMAJ 2007; 176 (11) 1589-1594
    CrossrefPubMedGoogle Scholar
  • 84 Keeling D, Baglin T, Tait C. , et al. British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin – fourth edition. Br J Haematol 2011; 154: 311-324
    CrossrefPubMedGoogle Scholar
  • 85 Hunt BJ, Allard S, Keeling D, Norfolk D, Stanworth SJ, Pendry K. ; British Committee for Standards in Haematology. A practical guideline for the haematological management of major haemorrhage. Br J Haematol 2015; 170 (06) 788-803
    CrossrefPubMedGoogle Scholar
  • 86 Hunt BJ, Neal MD, Stensballe J. Reversing anti-factor Xa agents and the unmet needs in trauma patients. Blood 2018; 132 (23) 2441-2445
    PubMedGoogle Scholar
  • 87 Bliden KP, Chaudhary R, Mohammed N. , et al. Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system. J Thromb Thrombolysis 2017; 43 (04) 437-445
    CrossrefPubMedGoogle Scholar
  • 88 Connolly SJ, Crowther M, Eikelboom JW. , et al; ANNEXA-4 Investigators. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med 2019; 380 (14) 1326-1335
    CrossrefPubMedGoogle Scholar
  • 89 Gilstad C, Roschewski M, Wells J. , et al. Fatal transfusion-associated graft-versus-host disease with concomitant immune hemolysis in a group A combat trauma patient resuscitated with group O fresh whole blood. Transfusion 2012; 52 (05) 930-935
    CrossrefPubMedGoogle Scholar
  • 90 Seheult JN, Bahr M, Anto V. , et al. Safety profile of uncrossmatched, cold-stored, low-titer, group O+ whole blood in civilian trauma patients. Transfusion 2018; 58 (10) 2280-2288
    CrossrefPubMedGoogle Scholar
  • 91 Brohi K, Gruen RL, Holcomb JB. Why are bleeding trauma patients still dying?. Intensive Care Med 2019; 45 (05) 709-711
    CrossrefPubMedGoogle Scholar
  • 92 Mira JC, Brakenridge SC, Moldawer LL, Moore FA. Persistent inflammation, immunosuppression and catabolism syndrome. Crit Care Clin 2017; 33 (02) 245-258
    CrossrefPubMedGoogle Scholar