Coagulation Abnormalities in the Trauma Patient: The Role of Point-of-Care Thromboelastography

ABSTRACT

Current recommendations for resuscitation of the critically injured patient are limited by a lack of point-of-care (POC) assessment of coagulation status. Accordingly, the potential exists for indiscriminant blood component administration. Furthermore, although thromboembolic events have been described shortly after injury, the time sequence of post-injury coagulation changes is unknown. Our current understanding of hemostasis has shifted from a classic view, in which coagulation was considered a chain of catalytic enzyme reactions, to the cell-based model (CBM), representing the interplay between the cellular and plasma components of clot formation. Thromboelastography (TEG), a time-sensitive dynamic assay of the viscoelastic properties of blood, closely parallels the CBM, permitting timely, goal-directed restoration of hemostasis via POC monitoring of coagulation status. TEG-based therapy allows for goal-directed blood product administration in trauma, with potential avoidance of the complications resulting from overzealous component administration, as well as the ability to monitor post-injury coagulation status and thromboprophylaxis. This overview addresses coagulation status and thromboprophylaxis management in the trauma patient and the emerging role of POC TEG.

KEYWORDS

Coagulopathy - hypercoagulability - trauma - cell-based model - thromboelastography - massive transfusion - transfusion ratio

REFERENCES

• 1 Sauaia A, Moore F A, Moore E E et al.. Epidemiology of trauma deaths: a reassessment.  J Trauma. 1995;  38 185-193
• 2 Kauvar D S, Lefering R, Wade C E. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations.  J Trauma. 2006;  60(6, Suppl) S3-S11
• 3 Cosgriff N, Moore E E, Sauaia A, Kenny-Moynihan M, Burch J M, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited.  J Trauma. 1997;  42(5) 857-861 discussion 861-862
• 4 MacLeod J B, Lynn M, McKenney M G, Cohn S M, Murtha M. Early coagulopathy predicts mortality in trauma.  J Trauma. 2003;  55(1) 39-44
• 5 Kashuk J L, Moore E E, Millikan J S, Moore J B. Major abdominal vascular trauma—a unified approach.  J Trauma. 1982;  22(8) 672-679
• 6 Tieu B H, Holcomb J B, Schreiber M A. Coagulopathy: its pathophysiology and treatment in the injured patient.  World J Surg. 2007;  31(5) 1055-1064
• 7 Kashuk J L, Moore E E, Sawyer M et al. Primary fibrinolysis is integral in the pathogenesis of acute coagulopathy of trauma. Paper presented at: American Surgical Association 130th Annual Meeting, 2010 Chicago, IL;
• 8 Brohi K, Cohen M J, Ganter M T, Matthay M A, Mackersie R C, Pittet J F. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?.  Ann Surg. 2007;  245(5) 812-818
• 9 Rossaint R, Cerny V, Coats T J et al.. Key issues in advanced bleeding care in trauma.  Shock. 2006;  26(4) 322-331
• 10 Spivey M, Parr M J. Therapeutic approaches in trauma-induced coagulopathy.  Minerva Anestesiol. 2005;  71(6) 281-289
• 11 MacLeod J B. Trauma and coagulopathy: a new paradigm to consider.  Arch Surg. 2008;  143(8) 797-801
• 12 Kashuk J L, Moore E E, Johnson J L et al.. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer?.  J Trauma. 2008;  65(2) 261-270, discussion 270–271
• 13 Amara U, Rittirsch D, Flierl M et al.. Interaction between the coagulation and complement system.  Adv Exp Med Biol. 2008;  632 71-79
• 14 Kapsch D N, Metzler M, Harrington M, Mitchell F L, Silver D. Fibrinolytic response to trauma.  Surgery. 1984;  95(4) 473-478
• 15 Gando S, Tedo I, Kubota M. Posttrauma coagulation and fibrinolysis.  Crit Care Med. 1992;  20(5) 594-600
• 16 Moore E E, Moore F A, Fabian T C PolyHeme Study Group et al. Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial.  J Am Coll Surg. 2009;  208(1) 1-13
• 17 Maegele M, Lefering R, Yucel N AG Polytrauma of the German Trauma Society (DGU) et al. Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients.  Injury. 2007;  38(3) 298-304
• 18 Furie B, Furie B C. Mechanisms of thrombus formation.  N Engl J Med. 2008;  359(9) 938-949
• 19 Cannon W B, Fraser J, Cowell E. The preventive treatment of wound shock.  JAMA. 1918;  70 618-621
• 20 Schreiber M A, Differding J S, Thorborg P, Mayberry J C, Mullins R J. Hypercoagulability is most prevalent early after injury and in female patients.  J Trauma. 2005;  58(3) 475-480 discussion 480-481
• 21 Kashuk J L, Moore E E, Sabel A et al.. Rapid thrombelastography (r-TEG) identifies hypercoagulability and predicts thromboembolic events in surgical patients.  Surgery. 2009;  146(4) 764-772 discussion 772-774
• 22 Attia J, Ray J G, Cook D J, Douketis J, Ginsberg J S, Geerts W H. Deep vein thrombosis and its prevention in critically ill adults.  Arch Intern Med. 2001;  161(10) 1268-1279
• 23 O'Malley K F, Ross S E. Pulmonary embolism in major trauma patients.  J Trauma. 1990;  30(6) 748-750
• 24 Ramacciotti E, Myers Jr D D, Wrobleski S K et al.. P-selectin/ PSGL-1 inhibitors versus enoxaparin in the resolution of venous thrombosis: a meta-analysis.  Thromb Res. 2010;  125(4) e138-e142
• 25 López J A, Kearon C, Lee A Y. Deep venous thrombosis.  Hematology Am Soc Hematol Educ Program. 2004;  439-456
• 26 Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins.  J Clin Pathol. 1974;  27(7) 517-528
• 27 Kim Y, Nakase H, Nagata K, Sakaki T, Maeda M, Yamamoto K. Observation of arterial and venous thrombus formation by scanning and transmission electron microscopy.  Acta Neurochir (Wien). 2004;  146(1) 45-51 discussion 51
• 28 Myers Jr D D, Rectenwald J E, Bedard P W et al.. Decreased venous thrombosis with an oral inhibitor of P selectin.  J Vasc Surg. 2005;  42(2) 329-336
• 29 Hoffman M, Monroe III D M. A cell-based model of hemostasis.  Thromb Haemost. 2001;  85(6) 958-965
• 30 McPherson M A, Pincus M R. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, PA; W.B. Saunders 2006
• 31 Lucas C E, Ledgerwood A M. Clinical significance of altered coagulation tests after massive transfusion for trauma.  Am Surg. 1981;  47(3) 125-130
• 32 Brummel K E, Paradis S G, Butenas S, Mann K G. Thrombin functions during tissue factor-induced blood coagulation.  Blood. 2002;  100(1) 148-152
• 33 Martini W Z. Coagulopathy by hypothermia and acidosis: mechanisms of thrombin generation and fibrinogen availability.  J Trauma. 2009;  67(1) 202-208 discussion 208-209
• 34 Ferrara A, MacArthur J D, Wright H K, Modlin I M, McMillen M A. Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion.  Am J Surg. 1990;  160(5) 515-518
• 35 Counts R B, Haisch C, Simon T L, Maxwell N G, Heimbach D M, Carrico C J. Hemostasis in massively transfused trauma patients.  Ann Surg. 1979;  190(1) 91-99
• 36 Lucas C E, Ledgerwood A M. Clinical significance of altered coagulation tests after massive transfusion for trauma.  Am Surg. 1981;  47(3) 125-130
• 37 Opal S M, Esmon C T. Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis.  Crit Care. 2003;  7(1) 23-38
• 38 Lier H, Krep H, Schroeder S, Stuber F. Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma.  J Trauma. 2008;  65(4) 951-960
• 39 Quaknine-Orlando B, Samama C M, Riou B et al.. Role of the hematocrit in a rabbit model of arterial thrombosis and bleeding.  Anesthesiology. 1999;  90(5) 1454-1461
• 40 Turitto V T, Weiss H J. Red blood cells: their dual role in thrombus formation.  Science. 1980;  207(4430) 541-543
• 41 Aucar J A, Isaak E, Anthony D. The effect of red blood cell age on coagulation.  Am J Surg. 2009;  198(6) 900-904
• 42 Kashuk J L, Moore E E, Johnson J L et al.. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer?.  J Trauma. 2008;  65(2) 261-270 discussion 270-271
• 43 Holcomb J B, Wade C E, Michalek J E et al.. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.  Ann Surg. 2008;  248(3) 447-458
• 44 Borgman M A, Spinella P C, Perkins J G et al.. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital.  J Trauma. 2007;  63(4) 805-813
• 45 Gonzalez E A, Moore F A, Holcomb J B et al.. Fresh frozen plasma should be given earlier to patients requiring massive transfusion.  J Trauma. 2007;  62(1) 112-119
• 46 Gunter Jr O L, Au B K, Isbell J M, Mowery N T, Young P P, Cotton B A. Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival.  J Trauma. 2008;  65(3) 527-534
• 47 Davenport R, De'Ath H, Manson J et al. Coagulation response to different plasma:red cell ratios in trauma transfusion. Paper presented at: Annual Meeting of the Eastern Association for the Surgery of Trauma 2010 Naples, FL;
• 48 Scalea T M, Bochicchio K M, Lumpkins K et al.. Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients.  Ann Surg. 2008;  248(4) 578-584
• 49 Snyder C W, Weinberg J A, McGwin Jr G et al.. The relationship of blood product ratio to mortality: survival benefit or survival bias?.  J Trauma. 2009;  66(2) 358-362 discussion 362-364
• 50 Magnotti L J, Zarzaur B L, Croce M A et al.. Improved survival after hemostatic resuscitation: does the emperor have no clothes?.  J Trauma. 2010;  , In press
• 51 Perkins J G, Cap A P, Andrew C P 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
• 52 Ciavarella D, Reed R L, Counts R B et al.. Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient.  Br J Haematol. 1987;  67 365-368
• 53 Hiippala S T, Myllylä G J, Vahtera E M. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates.  Anesth Analg. 1995;  81(2) 360-365
• 54 Zuckerman L, Cohen E, Vagher J P, Woodward E, Caprini J A. Comparison of thrombelastography with common coagulation tests.  Thromb Haemost. 1981;  46(4) 752-756
• 55 Ellis T C, Nielsen V G, Marques M B et al.. Thrombelastographic measures of clot propagation: a comparison of alpha with the maximum rate of thrombus generation.  Blood Coagul Fibrinolysis. 2007;  18 45-48
• 56 Marik P E, Corwin H L. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature.  Crit Care Med. 2008;  36(9) 2667-2674
• 57 Moore F A, Moore E E, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure.  Arch Surg. 1997;  132(6) 620-624 discussion 624-625
• 58 Watson G A, Sperry J L, Rosengart M R Inflammation and Host Response to Injury Investigators et al. Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome.  J Trauma. 2009;  67(2) 221-227 discussion 228-230
• 59 Johnson J L, Moore E E, Kashuk J L. Early transfusion of FFP is independently associated with postinjury multiple organ failure.  Arch Surg. 2010;  , In press
• 60 Khan H, Belsher J, Yilmaz M et al.. Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients.  Chest. 2007;  131(5) 1308-1314
• 61 Flesland O. A comparison of complication rates based on published haemovigilance data.  Intensive Care Med. 2007;  33(Suppl 1) S17-S21
• 62 Artang R, Frandsen N J, Nielsen J D. Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study.  Thromb J. 2009;  10(7) 14
• 63 Van P Y, Cho S D, Underwood S J, Morris M S, Watters J M, Schreiber M A. Thrombelastography versus AntiFactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients.  J Trauma. 2009;  66(6) 1509-1515 discussion 1515-1517
• 64 Geerts W H, Bergqvist D, Pineo G F et al.. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.  Chest. 2008;  133(6 Suppl) 381S-453S
• 65 Weitz J I. Low-molecular-weight heparins.  N Engl J Med. 1997;  337(10) 688-698
• 66 Patel R, Cook D J, Meade M O Burden of Illness in venous ThromboEmbolism in Critical care (BITEC) Study Investigators et al. Burden of illness in venous thromboembolism in critical care: a multicenter observational study.  J Crit Care. 2005;  20(4) 341-347
• 67 Ibrahim E H, Iregui M, Prentice D, Sherman G, Kollef M H, Shannon W. Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis.  Crit Care Med. 2002;  30(4) 771-774
• 68 Geerts W H, Jay R M, Code K I et al.. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma.  N Engl J Med. 1996;  335(10) 701-707
• 69 Hartert H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren.  Klin Wochenschr. 1948;  16(37–38) 577-583
• 70 De Nicola P. Thromboelastography. Oxford, United Kingdom; Blackwell Scientific 1957
• 71 Kang Y G, Martin D J, Marquez J et al.. Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation.  Anesth Analg. 1985;  64(9) 888-896
• 72 Tuman K J, Spiess B D, McCarthy R J, Ivankovich A D. Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass.  Anesth Analg. 1989;  69(1) 69-75
• 73 Gibbs N M, Crawford G P, Michalopoulos N. Thrombelastographic patterns following abdominal aortic surgery.  Anaesth Intensive Care. 1994;  22(5) 534-538
• 74 Chen A, Teruya J. Global hemostasis testing thromboelastography: old technology, new applications.  Clin Lab Med. 2009;  29(2) 391-407
• 75 Khurana S, Mattson J C, Westley S, O'Neill W W, Timmis G C, Safian R D. Monitoring platelet glycoprotein IIb/IIIa-fibrin interaction with tissue factor-activated thromboelastography.  J Lab Clin Med. 1997;  130(4) 401-411
• 76 Nielsen V G, Geary B T, Baird M S. Evaluation of the contribution of platelets to clot strength by thromboelastography in rabbits: the role of tissue factor and cytochalasin D.  Anesth Analg. 2000;  91(1) 35-39
• 77 Michelson A D. Methods for the measurement of platelet function.  Am J Cardiol. 2009;  103(3, Suppl) 20A-26A
• 78 Nielsen V G. Beyond cell based models of coagulation: analyses of coagulation with clot “lifespan” resistance-time relationships.  Thromb Res. 2008;  122(2) 145-152
• 79 Sørensen B, Johansen P, Christiansen K, Woelke M, Ingerslev J. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation.  J Thromb Haemost. 2003;  1(3) 551-558
• 80 Rivard G E, Brummel-Ziedins K E, Mann K G, Fan L, Hofer A, Cohen E. Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography.  J Thromb Haemost. 2005;  3(9) 2039-2043
• 81 Gonzalez E, Kahuk J L, Moore E E, Silliman C. Differentiation of enzymatic from platelet hypercoagulability using the novel thrombelastography parameter delta.  J Surg Res. 2010;  , April 21 (Epub ahead of print)
• 82 Kheirabadi B S, Crissey J M, Deguzman R, Holcomb J B. In vivo bleeding time and in vitro thrombelastography measurements are better indicators of dilutional hypothermic coagulopathy than prothrombin time.  J Trauma. 2007;  62(6) 1352-1359 discussion 1359-1361
• 83 Park M S, Martini W Z, Dubick M A et al.. Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time.  J Trauma. 2009;  67(2) 266-275 discussion 275-276
• 84 Plotkin A J, Wade C E, Jenkins D H et al.. A reduction in clot formation rate and strength assessed by thromboelastography is indicative of transfusion requirements in patients with penetrating injuries.  J Trauma. 2008;  64(2 Suppl) S64-S68
• 85 Schöchl H, Frietsch T, Pavelka M, Jámbor C. Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry.  J Trauma. 2009;  67(1) 125-131
• 86 Nielsen V G. A comparison of the Thrombelastograph and the ROTEM.  Blood Coagul Fibrinolysis. 2007;  18(3) 247-252
• 87 Stahel P F, Moore E E, Schreier S L, Flierl M A, Kashuk J L. Transfusion strategies in postinjury coagulopathy.  Curr Opin Anaesthesiol. 2009;  22(2) 289-298
• 88 Bolliger D, Szlam F, Molinaro R J, Rahe-Meyer N, Levy J H, Tanaka K A. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model.  Br J Anaesth. 2009;  102(6) 793-799
• 89 Vorweg M, Hartmann B, Knüttgen D, Jahn M C, Doehn M. Management of fulminant fibrinolysis during abdominal aortic surgery.  J Cardiothorac Vasc Anesth. 2001;  15(6) 764-767
• 90 Kang Y. Thromboelastography in liver transplantation.  Semin Thromb Hemost. 1995;  21(Suppl 4) 34-44
• 91 Ray W A, Stein C M. The aprotinin story—is BART the final chapter?.  N Engl J Med. 2008;  358(22) 2398-2400
• 92 Ide M, Bolliger D, Taketomi T, Tanaka K A. Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy in cardiac surgery.  J Anesth. 2010;  24(1) 96-106
• 93 Stamou S C, Reames M K, Skipper E et al.. Aprotinin in cardiac surgery patients: is the risk worth the benefit?. Presented at: The Society of Critical Care Medicine January 2008 Nashville, TN;
• 94 Zumwinkle L, Kashuk J, Moore E E. Rapid thrombelastography differentiates primary from secondary fibrinolysis.  Crit Care Med. 2008;  36 187-190
• 95 Kashuk J L, Moore E E, Wohlauer M et al.. Point of care rapid thrombelastography improves management of life threatening post-injury coagulopathy. Paper presented at: American Association for the Surgery of Trauma 68th Annual Meeting October 2009 Pittsburgh, PA;
• 96 Kaur J, Jones N, Mallett S. Thrombelastography Platelet Mapping is a useful preoperative tool in surgical patients taking antiplatelet medication.  Br J Anaesth. 2009;  103(2) 304 author reply 304-305
• 97 Agarwal S, Coakley M, Coakely M, Reddy K, Riddell A, Mallett S. Quantifying the effect of antiplatelet therapy: a comparison of the platelet function analyzer (PFA-100) and modified thromboelastography (mTEG) with light transmission platelet aggregometry.  Anesthesiology. 2006;  105(4) 676-683
• 98 Tantry U S, Bliden K P, Gurbel P A. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation.  J Am Coll Cardiol. 2005;  46(9) 1705-1709
• 99 Spalding G J, Hartrumpf M, Sierig T, Oesberg N, Kirschke C G, Albes J M. Bedside thrombelastography. Cost reduction in cardiac surgery [in German].  Anaesthesist. 2007;  56(8) 765-771
• 100 Spiess B D, Gillies B S, Chandler W, Verrier E. Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients.  J Cardiothorac Vasc Anesth. 1995;  9(2) 168-173
• 101 Knudson M M, Ikossi D G, Khaw L, Morabito D, Speetzen L S. Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank.  Ann Surg. 2004;  240(3) 490-496 discussion 496-498