Goal-directed Coagulation Management in Major Trauma

  • H. Schoechl
  • W. Voelckel
  • C. Solomon
Part of the Annual Update in Intensive Care and Emergency Medicine 2011 book series (AUICEM, volume 1)


Severe tissue trauma is frequently associated with hemorrhagic shock and subsequent pronounced coagulopathy [1]. Uncontrolled bleeding is the second most common cause of death, and hemorrhage is directly responsible for 40 % of all trauma-related deaths [2]. Coagulopathy can be detected with standard coagulation tests immediately after arrival in the emergency room (ER) in approximately 25–35 % of all trauma patients [1], [2]. Moreover, early trauma-induced coagulopathy is associated with a 4-fold increase in mortality [1]. Blood coagulation monitoring is essential in order to assess the underlying coagulation disorder and to tailor hemostatic treatment. Thromboelastometry (TEM) and thrombelastography (TEG) are promising point-of-care technologies providing rapid information on the initiation process of clot formation, clot quality, and stability of the clot [3].


Trauma Patient Fresh Freeze Plasma Thrombin Generation Major Trauma Massive Transfusion 
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.


  1. 1.
    Brohi K, Cohen MJ, Davenport RA (2007) Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care 13: 680–685PubMedCrossRefGoogle Scholar
  2. 2.
    Sauaia A, Moore FA, Moore EE, et al (1995) Epidemiology of trauma deaths: a reassessment. J Trauma 38: 185–193PubMedCrossRefGoogle Scholar
  3. 3.
    Kashuk JL, Moore EE, Le T, et al (2009) Noncitrated whole blood is optimal for evaluation of postinjury coagulopathy with point-of-care rapid thrombelastography. J Surg Res 156: 133–138PubMedCrossRefGoogle Scholar
  4. 4.
    Schochl H, Nienaber U, Hofer G, et al (2010) Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM(R))-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 14: R55PubMedCrossRefGoogle Scholar
  5. 5.
    Brohi K, Cohen MJ, Ganter MT, et al (2007) Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg 245: 812–818PubMedCrossRefGoogle Scholar
  6. 6.
    Carroll RC, Craft RM, Langdon RJ, et al (2009) Early evaluation of acute traumatic coagulopathy by thrombelastography. Transl Res 154: 34–39PubMedCrossRefGoogle Scholar
  7. 7.
    Levrat A, Gros A, Rugeri L, et al (2008) Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth 100: 792–797PubMedCrossRefGoogle Scholar
  8. 8.
    Schochl H, Frietsch T, Pavelka M, Jambor C (2009) Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma 67: 125–131PubMedCrossRefGoogle Scholar
  9. 9.
    Maegele M, Lefering R, Yucel N, et al (2007) Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury 38: 298–304PubMedCrossRefGoogle Scholar
  10. 10.
    Fries D, Innerhofer P, Reif C, et al (2006) The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in vitro model. Anesth Analg 102: 347–351PubMedCrossRefGoogle Scholar
  11. 11.
    Fenger-Eriksen C, Tonnesen E, Ingerslev J, Sorensen B (2009) Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy. J Thromb Haemost 7: 1099–1105PubMedCrossRefGoogle Scholar
  12. 12.
    Lowe GD, Rumley A, Mackie IJ (2004) Plasma fibrinogen. Ann Clin Biochem 41: 430–440PubMedCrossRefGoogle Scholar
  13. 13.
    Hiippala ST, Myllyla GJ, Vahtera EM (1995) Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 81: 360–365PubMedCrossRefGoogle Scholar
  14. 14.
    Lampl L, Seifried E, Tisch M, et al (1992) [Hemostatic disorders following polytrauma—the role of physiologic coagulation inhibitors during the preclinical phase]. Anasthesiol Intensivmed Notfallmed Schmerzther 27: 31–36PubMedCrossRefGoogle Scholar
  15. 15.
    Fries D, Martini WZ (2010) Role of fibrinogen in trauma-induced coagulopathy. Br J Anaesth 105: 116–121PubMedCrossRefGoogle Scholar
  16. 16.
    Wang HE, Callaway CW, Peitzman AB, Tisherman SA (2005) Admission hypothermia and outcome after major trauma. Crit Care Med 33: 1296–1301PubMedCrossRefGoogle Scholar
  17. 17.
    Jurkovich GJ, Greiser WB, Luterman A, Curreri PW (1987) Hypothermia in trauma victims: an ominous predictor of survival. J Trauma 27: 1019–1024PubMedCrossRefGoogle Scholar
  18. 18.
    Wolberg AS, Meng ZH, Monroe DM, 3rd, Hoffman M (2004) A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma 56: 1221–1228PubMedCrossRefGoogle Scholar
  19. 19.
    Cosgriff N, Moore EE, Sauaia A, et al (1997) Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma 42: 857–861PubMedCrossRefGoogle Scholar
  20. 20.
    Meng ZH, Wolberg AS, Monroe DM, 3rd, Hoffman M (2003) The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients. J Trauma 55: 886–891PubMedCrossRefGoogle Scholar
  21. 21.
    Martini WZ (2009) Coagulopathy by hypothermia and acidosis: mechanisms of thrombin generation and fibrinogen availability. J Trauma 67: 202–208PubMedCrossRefGoogle Scholar
  22. 22.
    Kashuk JL, Moore EE, Sawyer M, et al (2010) Postinjury coagulopathy management: goal directed resuscitation via POC thrombelastography. Ann Surg 251: 604–614PubMedCrossRefGoogle Scholar
  23. 23.
    Toulon P, Ozier Y, Ankri A, et al (2009) Point-of-care versus central laboratory coagulation testing during haemorrhagic surgery. A multicenter study. Thromb Haemost 101: 394–401PubMedGoogle Scholar
  24. 24.
    Dzik WH (2004) Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rep 3: 324–330PubMedGoogle Scholar
  25. 25.
    Dempfle CE, Borggrefe M (2008) Point of care coagulation tests in critically ill patients. Semin Thromb Hemost 34: 445–450PubMedCrossRefGoogle Scholar
  26. 26.
    Christensen TD, Larsen TB, Jensen C, Maegaard M, Sorensen B (2009) International normalised ratio (INR) measured on the CoaguChek S and XS compared with the laboratory for determination of precision and accuracy. Thromb Haemost 101: 563–569PubMedGoogle Scholar
  27. 27.
    Hoffman M, Monroe DM, 3rd (2001) A cell-based model of hemostasis. Thromb Haemost 85: 958–965PubMedGoogle Scholar
  28. 28.
    Lang T, Johanning K, Metzler H, et al (2009) The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. Anesth Analg 108: 751–758PubMedCrossRefGoogle Scholar
  29. 29.
    Mann KG, Brummel K, Butenas S (2003) What is all that thrombin for? J Thromb Haemost 1: 1504–1514PubMedCrossRefGoogle Scholar
  30. 30.
    Luddington RJ (2005) Thrombelastography/thromboelastometry. Clin Lab Haematol 27: 81–90PubMedCrossRefGoogle Scholar
  31. 31.
    Fenger-Eriksen C, Moore GW, Rangarajan S, Ingerslev J, Sorensen B (2010) Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders. Transfusion 50: 2571–2576PubMedCrossRefGoogle Scholar
  32. 32.
    Adam S, Karger R, Kretschmer V (2010) Photo-optical methods can lead to clinically relevant overestimation of fibrinogen concentration in plasma diluted with hydroxyethyl starch. Clin Appl Thromb Hemost 16: 461–471PubMedCrossRefGoogle Scholar
  33. 33.
    Schochl H, Forster L, Woidke R, Solomon C, Voelckel W (2010) Use of rotation thromboelastometry (ROTEM) to achieve successful treatment of polytrauma with fibrinogen concentrate and prothrombin complex concentrate. Anaesthesia 65: 199–203PubMedCrossRefGoogle Scholar
  34. 34.
    Kaufmann CR, Dwyer KM, Crews JD, Dols SJ, Trask AL (1997) Usefulness of thrombelastography in assessment of trauma patient coagulation. J Trauma 42: 716–720PubMedCrossRefGoogle Scholar
  35. 35.
    Plotkin AJ, Wade CE, Jenkins DH, et al (2008) A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma 64: S64–S68PubMedCrossRefGoogle Scholar
  36. 36.
    Rossaint R, Bouillon B, Cerny V, et al (2010) Management of bleeding following major trauma: an updated European guideline. Crit Care 14: R52PubMedCrossRefGoogle Scholar
  37. 37.
    Higa G, Friese R, O’Keeffe T, et al (2010) Damage control laparotomy: a vital tool once overused. J Trauma 69: 53–59PubMedCrossRefGoogle Scholar
  38. 38.
    Kowalenko T, Stern S, Dronen S, Wang X (1992) Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model. J Trauma 33: 349–353PubMedCrossRefGoogle Scholar
  39. 39.
    Sondeen JL, Coppes VG, Holcomb JB (2003) Blood pressure at which rebleeding occurs after resuscitation in swine with aortic injury. J Trauma 54: S110–S117PubMedCrossRefGoogle Scholar
  40. 40.
    Bickell WH, Wall MJ, Jr., Pepe PE, et al (1994) Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 331: 1105–1109PubMedCrossRefGoogle Scholar
  41. 41.
    Dutton RP, Mackenzie CF, Scalea TM (2002) Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma 52: 1141–1146PubMedCrossRefGoogle Scholar
  42. 42.
    Nascimento B, Callum J, Rubenfeld G, et al (2010) Clinical review: Fresh frozen plasma in massive bleedings — more questions than answers. Crit Care 14: 202PubMedCrossRefGoogle Scholar
  43. 43.
    Holcomb JB (2007) Damage control resuscitation. J Trauma 62: S36–S37PubMedCrossRefGoogle Scholar
  44. 44.
    Murad MH, Stubbs JR, Gandhi MJ, et al (2010) The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 50: 1370–1383PubMedCrossRefGoogle Scholar
  45. 45.
    Chowdhury P, Saayman AG, Paulus U, Findlay GP, Collins PW (2004) Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 125: 69–73PubMedCrossRefGoogle Scholar
  46. 46.
    Shander A, Hofmann A, Ozawa S, et al (2010) Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion 50: 753–765PubMedCrossRefGoogle Scholar
  47. 47.
    Shuja F, Shults C, Duggan M, et al (2008) Development and testing of freeze-dried plasma for the treatment of trauma-associated coagulopathy. J Trauma 65: 975–985PubMedCrossRefGoogle Scholar
  48. 48.
    Scalea TM, Bochicchio KM, Lumpkins K, et al (2008) Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients. Ann Surg 248: 578–584PubMedGoogle Scholar
  49. 49.
    Snyder CW, Weinberg JA, McGwin G Jr, et al (2009) The relationship of blood product ratio to mortality: survival benefit or survival bias? J Trauma 66: 358–362PubMedCrossRefGoogle Scholar
  50. 50.
    Chaiwat O, Lang JD, Vavilala MS, et al (2009) Early packed red blood cell transfusion and acute respiratory distress syndrome after trauma. Anesthesiology 110: 351–360PubMedCrossRefGoogle Scholar
  51. 51.
    Watson GA, Sperry JL, Rosengart MR, et al (2009) Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome. J Trauma 67: 221–227PubMedCrossRefGoogle Scholar
  52. 52.
    Sarani B, Dunkman WJ, Dean L, et al (2008) Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Crit Care Med 36: 1114–1118PubMedCrossRefGoogle Scholar
  53. 53.
    Riskin DJ, Tsai TC, Riskin L, et al (2009) Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg 209: 198–205PubMedCrossRefGoogle Scholar
  54. 54.
    Solomon C, Pichlmaier U, Schoechl H, et al (2010) Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth 104: 555–562PubMedCrossRefGoogle Scholar
  55. 55.
    Brenni M, Worn M, Bruesch M, Spahn DR, Ganter MT (2010) Successful rotational thromboelastometry-guided treatment of traumatic haemorrhage, hyperfibrinolysis and coagulopathy. Acta Anaesthesiol Scand 54: 111–117PubMedCrossRefGoogle Scholar
  56. 56.
    Fenger-Eriksen C, Ingerslev J, Sorensen B (2009) Fibrinogen concentrate—a potential universal hemostatic agent. Expert Opin Biol Ther 9: 1325–1333PubMedCrossRefGoogle Scholar
  57. 57.
    Sorensen B, Bevan D (2010) A critical evaluation of cryoprecipitate for replacement of fibrinogen. Br J Haematol 149: 834–843PubMedCrossRefGoogle Scholar
  58. 58.
    Stinger HK, Spinella PC, Perkins JG, et al (2008) The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital. J Trauma 64: S79–S85PubMedCrossRefGoogle Scholar
  59. 59.
    Dickneite G, Pragst I, Joch C, Bergman GE (2009) Animal model and clinical evidence indicating low thrombogenic potential of fibrinogen concentrate (Haemocomplettan P). Blood Coagul Fibrinolysis 20: 535–540PubMedCrossRefGoogle Scholar
  60. 60.
    Fenger-Eriksen C, Jensen TM, Kristensen BS, et al (2009) Fibrinogen substitution improves whole blood clot firmness after dilution with hydroxyethyl starch in bleeding patients undergoing radical cystectomy: a randomized, placebo-controlled clinical trial. J Thromb Haemost 7: 795–802PubMedCrossRefGoogle Scholar
  61. 61.
    Karlsson M, Ternstrom L, Hyllner M, et al (2009) Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study. Thromb Haemost 102: 137–144PubMedGoogle Scholar
  62. 62.
    Schochl H, Posch A, Hanke A, Voelckel W, Solomon C (2010) High-dose fibrinogen concentrate for haemostatic therapy of a major trauma patient with recent clopidogrel and aspirin intake. Scand J Clin Lab Invest 70: 453–457PubMedCrossRefGoogle Scholar
  63. 63.
    Velik-Salchner C, Haas T, Innerhofer P, et al (2007) The effect of fibrinogen concentrate on thrombocytopenia. J Thromb Haemost 5: 1019–1025PubMedCrossRefGoogle Scholar
  64. 64.
    Dunbar NM, Chandler WL (2009) Thrombin generation in trauma patients. Transfusion 49: 2652–2660PubMedCrossRefGoogle Scholar
  65. 65.
    Schreiber MA, Differding J, Thorborg P, Mayberry JC, Mullins RJ (2005) Hypercoagulability is most prevalent early after injury and in female patients. J Trauma 58: 475–480PubMedCrossRefGoogle Scholar
  66. 66.
    Baglin TP, Keeling DM, Watson HG (2006) Guidelines on oral anticoagulation (warfarin): third edition — 2005 update. Br J Haematol 132: 277–285PubMedCrossRefGoogle Scholar
  67. 67.
    Hirsh J, Guyatt G, Albers G, Harrington R, Schunemann H (2008) Antithrombotic and Thrombolytic Therapy. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 110S–112SPubMedCrossRefGoogle Scholar
  68. 68.
    Bruce D, Nokes TJ (2008) Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital. Crit Care 12: R105PubMedCrossRefGoogle Scholar
  69. 69.
    Schick KS, Fertmann JM, Jauch KW, Hoffmann JN (2009) Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care 13: R191PubMedCrossRefGoogle Scholar
  70. 70.
    Boffard KD, Riou B, Warren B, et al (2005) Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma 59: 8–15PubMedCrossRefGoogle Scholar
  71. 71.
    Hauser CJ, Boffard K, Dutton R, et al (2010) Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage. J Trauma 69: 489–500PubMedCrossRefGoogle Scholar
  72. 72.
    Shakur H, Roberts I, Bautista R, et al (2010) 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 376: 23–32PubMedCrossRefGoogle Scholar
  73. 73.
    Borgman MA, Spinella PC, Perkins JG, et al (2007) The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 63: 805–813PubMedCrossRefGoogle Scholar
  74. 74.
    Gunter OL, Jr., Au BK, Isbell JM, et al (2008) Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival. J Trauma 65: 527–534PubMedCrossRefGoogle Scholar
  75. 75.
    Maegele M, Lefering R, Paffrath T, et al (2008) Red-blood-cell to plasma ratios transfused during massive transfusion are associated with mortality in severe multiple injury: a retrospective analysis from the Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie. Vox Sang 95: 112–119PubMedCrossRefGoogle Scholar
  76. 76.
    Spinella PC, Perkins JG, Grathwohl KW, et al (2008) Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries. J Trauma 64: S69–S77PubMedCrossRefGoogle Scholar
  77. 77.
    Teixeira PG, Inaba K, Shulman I, et al (2009) Impact of plasma transfusion in massively transfused trauma patients. J Trauma 66: 693–697PubMedCrossRefGoogle Scholar
  78. 78.
    Zink KA, Sambasivan CN, Holcomb JB, Chisholm G, Schreiber MA (2009) A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study. Am J Surg 197: 565–570PubMedCrossRefGoogle Scholar
  79. 79.
    Kashuk JL, Moore EE, Johnson JL, et al (2008) Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? J Trauma 65: 261–270PubMedCrossRefGoogle Scholar
  80. 80.
    Sperry JL, Ochoa JB, Gunn SR, et al (2008) An FFP:PRBC transfusion ratio >/=1:1.5 is associated with a lower risk of mortality after massive transfusion. J Trauma 65: 986–993PubMedCrossRefGoogle Scholar
  81. 81.
    Cotton BA, Au BK, Nunez TC, et al (2009) Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications. J Trauma 66: 41–48PubMedCrossRefGoogle Scholar
  82. 82.
    Holcomb JB, Wade CE, Michalek JE, et al (2008) Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg 248: 447–458PubMedGoogle Scholar
  83. 83.
    Duchesne JC, Hunt JP, Wahl G, et al (2008) Review of current blood transfusions strategies in a mature level I trauma center: were we wrong for the last 60 years? J Trauma 65: 272–276PubMedCrossRefGoogle Scholar
  84. 84.
    Dente CJ, Shaz BH, Nicholas JM, et al (2009) Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center. J Trauma 66: 1616–1624PubMedCrossRefGoogle Scholar
  85. 85.
    Leese T, Holliday M, Heath D, Hall AW, Bell PR (1987) Multicentre clinical trial of low volume fresh frozen plasma therapy in acute pancreatitis. Br J Surg 74: 907–911PubMedCrossRefGoogle Scholar
  86. 86.
    Leese T, Holliday M, Watkins M, et al (1991) A multicentre controlled clinical trial of high-volume fresh frozen plasma therapy in prognostically severe acute pancreatitis. Ann R Coll Surg Engl 73: 207–214PubMedGoogle Scholar
  87. 87.
    van der Werff YD, van der Houwen HK, Heijmans PJ, et al (1997) Postpneumonectomy pulmonary edema. A retrospective analysis of incidence and possible risk factors. Chest 111: 1278–1284PubMedCrossRefGoogle Scholar
  88. 88.
    Martin RC, 2nd, Jarnagin WR, Fong Y, et al (2003) The use of fresh frozen plasma after major hepatic resection for colorectal metastasis: is there a standard for transfusion? J Am Coll Surg 196: 402–409PubMedCrossRefGoogle Scholar
  89. 89.
    Gajic O, Rana R, Mendez JL, et al (2004) Acute lung injury after blood transfusion in mechanically ventilated patients. Transfusion 44: 1468–1474PubMedCrossRefGoogle Scholar
  90. 90.
    Dara SI, Rana R, Afessa B, Moore SB, Gajic O (2005) Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit Care Med 33: 2667–2671PubMedCrossRefGoogle Scholar
  91. 91.
    Khan H, Belsher J, Yilmaz M, et al (2007) Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients. Chest 131: 1308–1314PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2011

Authors and Affiliations

  • H. Schoechl
    • 1
  • W. Voelckel
    • 2
  • C. Solomon
    • 3
  1. 1.Ludwig Boltzmann Institute of Experimental and Clinical TraumatologyAUVA Trauma Research CenterViennaAustria
  2. 2.Department of Anesthesiology and Intensive Care MedicineAUVA Trauma CenterSalzburgAustria
  3. 3.Department of Anesthesiology, Intensive Care and Perioperative MedicineUniversity HospitalSalzburgAustria

Personalised recommendations