Thromboelastometry guided therapy of severe bleeding

Summary

Both, severe haemorrhage and blood transfusion are associated with increased morbidity and mortality. Therefore, it is of particular importance to stop perioperative bleeding as fast and as possible to avoid unnecessary transfusion. Viscoelastic test (ROTEM® or TEG®) allow for early prediction of massive transfusion and goal-directed therapy with specific haemostatic drugs, coagulation factor concentrates, and blood products. Growing consensus points out, that plasma-based coagulation screening tests like aPTT and PT are inappropriate for monitoring coagulo pathy or guide transfusion therapy. Increasing evidence of more than 5000 surgical or trauma patients points towards the beneficial effects of a thrombelastography or –metry based approach in diagnosis and goal-directed therapy of perioperative massive haemorrhage. The Essener Runde task force is a group of clinicians of various specialties (anaesthesiology, intensive care, haemostaseology, haematology, internal medicine, transfusion medicine, surgery) interested in perioperative coagulation management. The ROTEM diagnostic algorithm of the Essener Runde task force was created to standardise and simplify the interpretation of ROTEM® results in perioperative settings and to present their possible implications for therapeutic interventions in severe bleeding. To exemplify, this text mainly focuses on coagulation management in trauma.

Zusammenfassung

Sowohl massive Blutungen wie auch Blut -(produkt)transfusionen sind mit einer Zunahme der Morbidität und Mortalität verbunden. Es ist daher von entscheidender Bedeutung, perioperative Blutungen schnellstmöglich zu stoppen und somit unnötige Transfusionen zu vermeiden. Viskoelastische Tests (ROTEM® oder TEG®) ermöglichen eine frühzeitige Er-kennung einer drohenden Massivtransfusion sowie die zielgerichtete Therapie mit spezifischen, die Hämostase fördernden Medika-menten, Gerinnungsfaktorkonzentraten und Blutprodukten. In zunehmender Einigkeit werden plasma-basierte Gerinnungstest wie aPTT und PT als ungeeignet zur Diagnostik einer Koagulopathie oder Steuerung der Transfusionstherapie angesehen. An mittler-weile über 5000 operativen und traumatischen Patienten konnte der sinnvolle Einsatz thrombelastometrischer und -grafischer Ver-fahren zur Diagnose und zielgerichteten Therapie massiver Blutungen gezeigt wer-den. Die “Essener Runde” ist eine Gruppe aus klinisch tätigen Medizinern verschiede-ner Disziplinen, die sich mit perioperativer Gerinnung beschäftigt. Der diagnostische ROTEM-Algorithmus der Essener Runde wurde entwickelt um eine Standardisierung und Vereinfachung der Interpretation von ROTEM® Ergebnissen im perioperativen Umfeld zu ermöglichen und die sich daraus erg-ebenen therapeutischen Optionen zubeschreiben. Der Text zeigt dies am Beispiel des Gerinnungsmanagements bei Poly traumata.

Keywords

Coagulopathy - haemorrhage - thromboelastometry - ROTEM

Schlüsselwörter

Koagulopathie - Massivblutung - Thromboelastometrie - ROTEM

• References

• 1 American Society of Anesthesiologists. Practice guidelines for perioperative blood transfusion and adjuvant therapies. Anesthesiology 2006; 105: 198-208.
• 2 AWMF. S3-Guideline on treatment of patients with severe and multiple injuries. www.awmf.org (accessed: Nov 1012)
• 3 Beekley AC. Damage control resuscitation. Crit Care Med 2008; 36: S267-S274.
• 4 Board of the German Medical Association on the Recommendation of the Scientific Advisory Board. Cross-sectional guidelines for therapy with blood components and plasma derivatives. Transfus Med Hemother 2009; 36: 351-492.
• 5 Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev 2011; 26: 1-13.
• 6 Bolliger D, Szlam F, Levy JH. et al. Haemodilutioninduced profibrinolytic state is mitigated by freshfrozen plasma. Br J Anaesth 2010; 104: 318-325.
• 7 Borgman MA, Spinella PC, Holcomb JB. et al. The effect of FFP:RBC ratio on morbidity and mortality in trauma patients based on transfusion prediction score. Vox Sang 2011; 101: 44-54.
• 8 Brohi K, Cohen MJ, Davenport RA. Acute coagulopathy of trauma. Curr Opin Crit Care 2007; 13: 680-685.
• 9 Brohi K, Cohen MJ, Ganter MT. et al. Acute coagulopathy of trauma. J Trauma 2008; 64: 1211-1217.
• 10 Bundesärztekammer BÄK. Cross-sectional Guidelines for Therapy with Blood Components and Plasma Derivatives. 4th ed.. (accessed: 2009)
• 11 Bunn F, Trivedi D, Ashraf S. Colloid solutions for fluid resuscitation. Cochrane Database Syst Rev. 2008CD001319.
• 12 Carling MS, Jeppsson A, Wessberg P. et al. Preoperative fibrinogen plasma concentration is associated with perioperative bleeding and transfusion requirements in scoliosis surgery. Spine 2011; 36: 549-555.
• 13 Chapman CE, Stainsby D, Jones H. et al. Ten years of hemovigilance reports of transfusion-related acute lung injury in the United Kingdom and the impact of preferential use of male donor plasma. Transfusion 2009; 49: 440-452.
• 14 Charbit B, Mandelbrot L, Samain E. et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost 2007; 05: 266-273.
• 15 Chowdhury P, Saayman AG, Paulus U. et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 2004; 125: 69-73.
• 16 Cotton BA, Au BK, Nunez TC. et al. Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications. J Trauma 2009; 66: 41-48.
• 17 Cotton BA, Faz G, Hatch QM. et al. Rapid thrombelastography delivers real-time results that predict transfusion within 1 hour of admission. J Trauma 2011; 71: 407-414.
• 18 Cotton BA, Gunter OL, Isbell J. et al. Damage control hematology. J Trauma 2008; 64: 1177-1182.
• 19 Davenport R, Manson J, De’ath H. et al. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med 2011; 39: 2652-2658.
• 20 Dente CJ, Shaz BH, Nicholas JM. et al. 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 2009; 66: 1616-1624.
• 21 Dirkmann D, Görlinger K, Dusse F. et al. Early thromboelastometric variables reliably predict maximum clot firmness in patients undergoing cardiac surgery. Br J Anaesth. 2012 DOI: 10.1093/bja/aes374.
• 22 Dirkmann D, Görlinger K, Gisbertz C. Factor XIII and tranexamic acid but not recombinant Factor VIIa attenuate tissue plasminogen activator–induced hyperfibrinolysis in human whole blood. Anesth Analg 2011; 114: 1182-1188.
• 23 Dirkmann D, Hanke AA, Gorlinger K. et al. Perioperative use of modified thrombelastography in factor XI deficiency. Acta Anaesthesiol Scand 2007; 51: 640-643.
• 24 Duchesne JC, Barbeau JM, Islam TM. et al. Damage control resuscitation. Am Surg 2011; 77: 201-206.
• 25 Ebinger T, Ruland A, Lakner M. et al. Validity, regulatory registration and approval of ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2010; 21: 106-107.
• 26 Fries D, Innerhofer P, Perger P. et al. Coagulation management in trauma-related massive bleeding. Anästhesiol Intensivmed Notfallmed Schmerzther 2010; 45: 552-561.
• 27 Fries D, Innerhofer P, Reif C. et al. The effect of fibrinogen substitution on reversal of dilutional coagulopathy. Anesth Analg 2006; 102: 347-351.
• 28 Frith D, Brohi K. The acute coagulopathy of trauma shock. Surgeon 2010; 08: 159-163.
• 29 Gilliss BM, Looney MR, Gropper MA. Reducing noninfectious risks of blood transfusion. Anesthesiology 2011; 115: 635-649.
• 30 Glance LG, Dick AW, Mukamel DB. et al. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. Anesthesiology 2011; 114: 283-292.
• 31 Gonzalez EA, Moore FA, Holcomb JB. et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J Trauma 2007; 62: 112-119.
• 32 Görlinger K. Differenzierte Therapie komplexer Gerinnungsstörungen. J Anästh Intensivmed 2005; 01: 120-124.
• 33 Görlinger K. Coagulation management during liver transplantation. Hämostaseologie 2006; 26: S64-S75.
• 34 Görlinger K. TED survey at the annual congress of the German Society of Anaesthesiology in Hamburg, May 5th, 2007. Mangement of trauma-induced coagulopathy. 2007
• 35 Görlinger K, Dirkmann D, Hanke A. ROTEMbased algorithm for point-of-care coagulation management in visceral surgery and liver transplantation. Liver Transplantation 2008; 14: S203-S204.
• 36 Görlinger K, Dirkmann D, Hanke A. et al. Firstline therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery. Anesthesiology 2011; 115: 1179-1191.
• 37 Görlinger K, Dirkmann D, Müller-Beißenhirtz H. et al. Thromboelastometry-based perioperative coagulation management in visceral surgery and liver transplantation. Liver Transplantation 2010; 16: S86.
• 38 Görlinger K, Dirkmann D, Solomon C. et al. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability. Br J Anaesth. 2012 DOI:10.1093/bja/aes374..
• 39 Görlinger K, Dirkmann D, Weber CF. et al. Algorithms for transfusion and coagulation management in massive haemorrhage. Anästh Intensivmed 2011; 52: 145-159.
• 40 Görlinger K, Fries D, Dirkmann D. et al. Reduction of fresh frozen plasma requirements by perioperative point-of-care coagulation management with early calculated goal-directed therapy. Transfus Med Hemother 2012; 39: 104-113.
• 41 Haas T, Spielmann N, Mauch J. et al. Comparison of thromboelastometry with standard plasmatic coagulation testing in paediatric surgery. Br J Anaesth 2012; 108: 36-41.
• 42 Hardy JF, De MP, Samama M. et al. Massive transfusion and coagulopathy. Can J Anaesth 2004; 51: 293-310.
• 43 Hartert H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wochenschr 1948; 16: 257-260.
• 44 Hartog CS, Reuter D, Loesche W. et al. Influence of hydroxyethyl starch 130/0.4 on hemostasis as measured by viscoelastic device analysis. Intensive Care Med 2011; 37: 1725-1737.
• 45 Hiippala ST, Myllyla GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 1995; 81: 360-365.
• 46 Ho AM, Dion PW, Yeung JH. et al. Prevalence of survivor bias in observational studies on fresh frozen plasma:erythrocyte ratios in trauma requiring massive transfusion. Anesthesiology 2012; 116: 716-728.
• 47 Hoffman M, Monroe D. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-965.
• 48 Innerhofer P. Fibrinogen and prothrombin complex concentrate for the management of massive bleeding. Wien Klin Wochenschr 2010; 122: S16-S17.
• 49 Jeger V, Zimmermann H, Exadaktylos AK. Can RapidTEG accelerate the search for coagulo-pathies in the patient with multiple injuries?. J Trauma 2009; 66: 1253-1257.
• 50 Johansson PI, Stensballe J. Effect of haemostatic control resuscitation on mortality in massively bleeding patients. Vox Sang 2009; 96: 111-118.
• 51 Johansson PI, Stissing T, Bochsen L. et al. Thrombelastography and tromboelastometry in assessing coagulopathy in trauma. Scand J Trauma Resusc Emerg Med 2009; 17: 45-53.
• 52 Karlsson M, Ternstrom L, Hyllner M. et al. Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery. Transfusion 2008; 48: 2152-2158.
• 53 Kashuk JL, Moore EE, Johnson JL. et al. Postinjury life threatening coagulopathy. J Trauma 2008; 65: 261-270.
• 54 Kashuk JL, Moore EE, Sawyer M. et al. Postinjury coagulopathy management: goal directed resuscitation via POC thrombelastography. Ann Surg 2010; 251: 604-614.
• 55 Kashuk JL, Moore EE, Sawyer M. et al. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg 2010; 252: 434-442.
• 56 Kawasaki J, Katori N, Kodaka M. et al. Electron microscopic evaluations of clot morphology during thrombelastography. Anesth Analg 2004; 99: 1440-1444.
• 57 Kirchner C, Görlinger K, Dirkmann D. et al. Safety and efficacy of prothrombin complex and fibrinogen concentrates in liver transplantation. Liver Transpl 2012; 18 (Suppl. 01) S189.
• 58 Knowles S, Cohen H. on behalf of the Serious Hazards of Transfusion Steering Group. The 2010 Annual SHOT Report. www.shotuk.org/wp-con tent/uploads/2011/10/SHOT-2010-Report1.pdf (accessed: 2011)
• 59 Kozek-Langenecker SA. Perioperative coagulation monitoring. Best Pract Res Clin Anaesthesiol 2010; 24: 27-40.
• 60 Lang T, Bauters A, Braun SL. et al. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2005; 16: 301-310.
• 61 Leemann H, Lustenberger T, Talving P. et al. The role of rotation thromboelastometry in early prediction of massive transfusion. J Trauma 2010; 69: 1403-1408.
• 62 Levrat A, Gros A, Rugeri L. et al. Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth 2008; 100: 792-797.
• 63 Levy JH. Antifibrinolytic therapy: new data and new concepts. Lancet 2010; 376: 3-4.
• 64 Lier H, Bottiger BW, Hinkelbein J. et al. Coagulation management in multiple trauma. Intensive Care Med 2011; 37: 572-582.
• 65 Lier H, Krep H, Schroeder S. et al. Preconditions of hemostasis in trauma. J Trauma 2008; 65: 951-960.
• 66 McDonald V, Ryland K. Coagulopathy in trauma: optimising haematological status. Trauma 2008; 10: 109-123.
• 67 McSwain NE, Champion HR, Fabian TC. et al. State of the art of fluid resuscitation 2010. J Trauma 2011; 70: S2-10.
• 68 Murthi SB, Stansbury LG, Dutton RP. et al. Transfusion medicine in trauma patients. Expert Rev Hematol 2011; 04: 527-537.
• 69 Nienaber U, Innerhofer P, Westermann I. et al. The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. Injury 2011; 42: 697-701.
• 70 Pezold M, Moore EE, Wohlauer M. et al. Viscoelastic clot strength predicts coagulation-related mortality within 15 minutes. Surgery 2012; 151: 48-54.
• 71 Rahe-Meyer N, Pichlmaier M, Haverich A. et al. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. Br J Anaesth 2009; 102: 785-792.
• 72 Rivard GE, Brummel-Ziedins KE, Mann KG. et al. Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography. J Thromb Haemost 2005; 03: 2039-2043.
• 73 Roback JD, Caldwell S, Carson J. et al. Evidencebased practice guidelines for plasma transfusion. Transfusion 2010; 50: 1227-1239.
• 74 Rossaint R, Bouillon B, Cerny V. et al. Management of bleeding following major trauma. Crit Care 2010; 14: R52.
• 75 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: 1342-1351.
• 76 Sakai T, Matsusaki T, Dai F. et al. Pulmonary thromboembolism during adult liver transplantation. Br J Anaesth 2012; 108: 469-477.
• 77 Sambasivan CN, Kunio NR, Nair PV. et al. High ratios of plasma and platelets to packed red blood cells do not affect mortality in nonmassively transfused patients. J Trauma 2011; 71: S329-S336.
• 78 Sarani B, Dunkman WJ, Dean L. et al. Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Crit Care Med 2008; 36: 1114-1118.
• 79 Schochl H, Frietsch T, Pavelka M. et al. Hyperfibrinolysis after major trauma. J Trauma 2009; 67: 125-131.
• 80 Schöchl H, Forster L, Woidke R. et al. Use of rotation thromboelastometry to achieve successful treatment of polytrauma with fibrinogen concentrate and prothrombin complex concentrate. Anaesthesia 2010; 65: 199-203.
• 81 Schöchl H, Maegele M, Solomon C. et al. Early and individualized goal-directed therapy for traumainduced coagulopathy. Scand J Trauma Resusc Emerg Med 2012; 20: 15.
• 82 Schöchl H, Nienaber U, Hofer G. et al. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 2010; 14: R55.
• 83 Schöchl H, Nienaber U, Maegele M. et al. Transfusion in trauma. Crit Care 2011; 15: R83.
• 84 Shakur H, Roberts I, Bautista R. et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2). Lancet 2010; 376: 23-32.
• 85 Spinella PC, Holcomb JB. Resuscitation and transfusion principles for traumatic hemorrhagic shock. Blood Rev 2009; 23: 231-240.
• 86 Stainsby D, Jones H, Asher D. et al. Serious hazards of transfusion. Transfus Med Rev 2006; 20: 273-282.
• 87 Stanworth SJ, Grant-Casey J, Lowe D. et al. The use of fresh-frozen plasma in England. Transfusion 2011; 51: 62-70.
• 88 Tauber H, Innerhofer P, Breitkopf R. et al. Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma. Br J Anaesth 2011; 107: 378-387.
• 89 Ternström L, Radulovic V, Karlsson M. et al. Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery. Thromb Res 2010; 126: e128-e133.
• 90 Theusinger OM, Baulig W, Asmis LM. et al. In vitro factor XIII supplementation increases clot firmness in rotation thromboelastometry. Thromb Haemost 2010; 104: 385-391.
• 91 Theusinger OM, Nurnberg J, Asmis LM. et al. Rotation thromboelastometry stability and reproducibility over time. Eur J Cardiothorac Surg 2010; 37: 677-683.
• 92 Tieu BH, Holcomb JB, Schreiber MA. Coagulopathy. World J Surg 2007; 31: 1055-1064.
• 93 Tripodi A, Anstee QM, Sogaard KK. et al. Hyper - coagulability in cirrhosis: causes and consequences. J Thromb Haemost 2011; 09: 1713-1723.
• 94 Van den Elsen MJ, Leenen LP, Kesecioglu J. Hemodynamic support of the trauma patient. Curr Opin Anaesthesiol 2010; 23: 269-275.
• 95 Watson GA, Sperry JL, Rosengart MR. 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: 221-227.
• 96 Waydhas C, Gorlinger K. Coagulation management in multiple trauma. Unfallchirurg 2009; 112: 942-950.
• 97 Weber CF, Görlinger K, Meininger D. et al. Pointof-care testing. Anesthesiology 2012; 117: 531-547.
• 98 Weber CF, Jambor C, Marquardt M. et al. Thrombelastometric detection of factor XIII deficiency. Anaesthesist 2008; 57: 487-490.
• 99 Wettstein P, Haeberli A, Stutz M. et al. Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding. Anesth Analg 2004; 99: 1564-1569.