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Diagnose von Gerinnungsstörungen mit Rotationsthromboelastometrie

  • M. Honickel
  • O. Grottke
Übersichten

Zusammenfassung

Hintergrund

Die Anwendung viskoelastischer Methoden der Gerinnungsdiagnostik, wie der Rotationsthromboelastometrie (ROTEM®, Tem International GmbH, München, Deutschland), bietet im Vergleich zu konventionellen Gerinnungstests, wie der Prothrombinzeit (PT) und der aktivierten partiellen Thromboplastinzeit (aPTT), perioperativ und für blutende Patienten prognoserelevante Vorteile. Durch die Verwendung von Vollblut liegen erste Ergebnisse innerhalb von 10–12 min vor, die eine qualitative und semiquantitative Aussage über die Kinetik des entstehenden Gerinnsels ermöglichen. Anhand dieser Informationen kann eine Koagulopathie, anstelle rein empirischer Ansätze, deutlich schneller zielgerichtet und individualisiert therapiert werden. Der Einsatz der ROTEM®-Diagnostik kann auch zu einem ressourcenschonenden Einsatz von allogenen Blutprodukten und Faktorenkonzentraten beitragen. Dadurch können das Auftreten transfusionsassoziierter Komplikationen vermieden und zudem die Kosten der Therapie gesenkt werden.

Ziel der Arbeit

Diese Arbeit dient als Einführung in die Methode der ROTEM®-Diagnostik und zeigt, wie mittels Kombination der verfügbaren Reagenzien eine schnelle Differenzialdiagnose häufiger Koagulopathien in der Praxis gelingen kann. Zudem sollen prognostischer Nutzen und methodische Grenzen der ROTEM®-Diagnostik dargestellt werden. Schließlich wird die Anwendung der ROTEM®-Diagnostik in ausgewählten operativen Fächern dargestellt und kritisch diskutiert.

Zusammenfassung

Die Rotationsthromboelastometrie ist eine geeignete Methode zur frühzeitigen Diagnostik präoperativer Blutungsrisiken sowie peri-/postoperativer und traumaassoziierter Hämorrhagien und kann algorithmenbasiert zu einer zielgerichteten Therapiesteuerung beitragen.

Schlüsselwörter

ROTEM Hyperfibrinolyse Traumatologie Koagulopathie Gerinnungsfaktorenkonzentrate 

Rotational thromboelastometry for the diagnosis of coagulation disorders

Abstract

Background

Compared to conventional coagulation assays, as prothrombin time (PT) or activated partial thromboplastin time (aPTT), viscoelastic methods of coagulation analysis, including rotational thromboelastometry (ROTEM®, Tem International GmbH, Munich, Germany), yield prognostic benefits. Results of ROTEM® in citrated whole blood could be generated within 10–12 min and allow for a qualitative and semiquantitative characterisation of clot kinetics. Based on ROTEM® results, the switch between empiric approaches of treating coagulopathy to a goal-directed approach could be accelerated. Introduction of ROTEM® reduces transfusion requirements and the need for single factor concentrates. Thus, ROTEM® reduces transfusion-related adverse events, and additionally implement therapeutic cost effectiveness.

Objectives

This review provides a short introduction in the methodology of ROTEM®, showing how the combination of assays with different commercially available ROTEM® reagents allows for rapid differential diagnosis of common coagulopathies in clinical practice. Furthermore, prognostic benefits and limitations of ROTEM® diagnostics are described. Finally, we discuss the potential fields of ROTEM® application in different surgical settings.

Conclusion

ROTEM® appears to be a contemporary, applicable and effective method in diagnosing coagulopathy and for subsequent algorithm-based goal-directed therapy.

Keywords

ROTEM Hyperfibrinolysis Traumatology Coagulopathy Coagulation factor concentrates 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

M. Honickel erhielt Reisekostenunterstützung von Böhringer Ingelheim. O. Grottke erhielt Studienförderung von Böhringer Ingelheim, Novo Nordisk, Biotest, CSL Behring und Nycomed sowie Honorare für Referate und Reisekostenunterstützung von CSL Behring, Böhringer Ingelheim, Bayer, Portola, Octapharma, Sanofi und Pfizer.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Adamzik M, Görlinger K, Peters J et al (2012) Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis. Crit Care 16:R204CrossRefGoogle Scholar
  2. 2.
    Afshari A, Wikkelsø A, Brok J et al (2011) Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion. Cochrane Database Syst Rev 3:CD007871Google Scholar
  3. 3.
    Alamo JM, León A, Mellado P et al (2013) Is “intra-operating room” thromboelastometry useful in liver transplantation? A case-control study in 303 patients. Transplant Proc 45:3637–3639CrossRefGoogle Scholar
  4. 4.
    Bienholz A, Canbay A, Saner FH (2016) Gerinnungsdiagnostik und -therapie bei Leberinsuffizienz. Med Klin Intensivmed Notfmed 111:224–234CrossRefGoogle Scholar
  5. 5.
    Chapman MP, Moore EE, Ramos CR et al (2013) Fibrinolysis greater than 3 % is the critical value for initiation of antifibrinolytic therapy. J Trauma Acute Care Surg 75:961–967CrossRefGoogle Scholar
  6. 6.
    Chapman MP, Moore EE, Moore HP et al (2015) Early TRAP pathway platelet inhibition predicts coagulopathic hemorrhage in trauma. Shock 43:S33Google Scholar
  7. 7.
    Collins PW, Lilley G, Bruynseels D et al (2014) Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood 124:1727–1736CrossRefGoogle Scholar
  8. 8.
    Davenport R, Manson J, De’Ath H et al (2011) Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med 39:2652–2658CrossRefGoogle Scholar
  9. 9.
    Dick A, Schwaiger M, Jámbor C (2010) Thromboelastography/-metry and external quality control – results of a pilot study. Hamostaseologie 30:91–95CrossRefGoogle Scholar
  10. 10.
    Dirkmann D, Görlinger K, Peters J (2014) Assessment of early thromboelastometric variables from extrinsically activated assays with and without aprotinin for rapid detection of fibrinolysis. Anesth Analg 119:533–542CrossRefGoogle Scholar
  11. 11.
    Dobson GP, Letson HL, Sharma R et al (2015) Mechanisms of early trauma-induced coagulopathy: The clot thickens or not? J Trauma Acute Care Surg 79:301–309CrossRefGoogle Scholar
  12. 12.
    Eller T, Busse J, Dittrich M et al (2014) Dabigatran, rivaroxaban, apixaban, argatroban and fondaparinux and their effects on coagulation POC and platelet function tests. Clin Chem Lab Med 52:835–844CrossRefGoogle Scholar
  13. 13.
    Fayed N, Mourad W, Yassen et al (2015) Preoperative thromboelastometry as a predictor of transfusion requirements during adult living donor liver transplantation. Transfus Med Hemother 42:99–108CrossRefGoogle Scholar
  14. 14.
    Frith D, Davenport R, Brohi K (2012) Acute traumatic coagulopathy. Curr Opin Anaesthesiol 25:229–234CrossRefGoogle Scholar
  15. 15.
    Görlinger K, Fries D, Dirkmann D et al (2012) Reduction of fresh frozen plasma requirements by perioperative point-of-care coagulation management with early calculated goal-directed therapy. Transfus Med Hemother 39:104–113CrossRefGoogle Scholar
  16. 16.
    Görlinger K, Dirkmann D, Solomon C et al (2013) Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability. Br J Anaesth 110:222–230CrossRefGoogle Scholar
  17. 17.
    Gonzalez E, Moore EE, Moore HB et al (2015) Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg 263(6):1051–1059. doi:10.1097/SLA.0000000000001608CrossRefGoogle Scholar
  18. 18.
    Grottke O, Braunschweig T, Spronk HM et al (2011) Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury. Blood 118:1943–1951CrossRefGoogle Scholar
  19. 19.
    Grottke O, van Ryn J, Spronk HM et al (2014) Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care 18:R27CrossRefGoogle Scholar
  20. 20.
    Haas T, Fries D, Tanaka KA et al (2015) Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence? Br J Anaesth 114:217–224CrossRefGoogle Scholar
  21. 21.
    Haas T, Görlinger K, Grassetto A et al (2014) Thromboelastometry for guiding bleeding management of the critical ill patient: a systematic review of the literature. Minerva Anestesiol 80:1320–1335PubMedGoogle Scholar
  22. 22.
    Haas T, Spielmann N, Restin T et al (2015) Higher fibrinogen concentrations for reduction of transfusion requirements during major paediatric surgery: a prospective randomised controlled trial. Br J Anaesth 115:234–243CrossRefGoogle Scholar
  23. 23.
    Hagemo JS, Christiaans SC, Stanworth SJ et al (2015) Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. Crit Care 19:97CrossRefGoogle Scholar
  24. 24.
    Hardy JF, De Moerloose P, Samama CM (2006) Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anaesth 53:S40–S58CrossRefGoogle Scholar
  25. 25.
    Harr JN, Moore EE, Chin TL et al (2015) Viscoelastic hemostatic fibrinogen assays detect fibrinolysis early. Eur J Trauma Emerg Surg 41:49–56CrossRefGoogle Scholar
  26. 26.
    Hartert H (1948) Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wochenschr 26:577–583CrossRefGoogle Scholar
  27. 27.
    Hochleitner G, Sutor K, Levett C et al (2015) Revisiting Hartert’s 1962 calculation of the physical constants of thrombelastography. Clin Appl Thromb Hemost. doi:10.1177/1076029615606531CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Honickel M, Maron B, van Ryn J et al (2015) Therapy with activated prothrombin complex concentrate is effective in reducing dabigatran-associated blood loss in a porcine polytrauma model. Thromb Haemost 115:271–284CrossRefGoogle Scholar
  29. 29.
    Hunt H, Stanworth S, Curry N et al (2015) Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding. Cochrane Database Syst Rev 2:CD010438. doi:10.1002/14651858.cd010438CrossRefGoogle Scholar
  30. 30.
    Katori N, Tanaka KA, Szlam F et al (2005) The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thromboelastography. Anesth Analg 100:1781–1785CrossRefGoogle Scholar
  31. 31.
    Koster A, Börgermann J, Gummert J et al (2014) Protamine overdose and its impact on coagulation, bleeding, and transfusions after cardiopulmonary bypass: results of a randomized double-blind controlled pilot study. Clin Appl Thromb Hemost 20:290–295CrossRefGoogle Scholar
  32. 32.
    Kozek-Langenecker SA, Afshari A, Albaladejo P et al (2013) Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 30:270–382CrossRefGoogle Scholar
  33. 33.
    Lancé MD (2015) A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis. Thromb J 13:1CrossRefGoogle Scholar
  34. 34.
    Larsen OH, Fenger-Eriksen C, Christiansen K et al (2011) Diagnostic performance and therapeutic consequence of thromboelastometry activated by kaolin versus a panel of specific reagents. Anesthesiology 115:294–302Google Scholar
  35. 35.
    Leon-Justel A, Noval-Padillo JA, Alvarez-Rios AI et al (2015) Point-of-care haemostasis monitoring during liver transplantation reduces transfusion requirements and improves patient outcome. Clin Chim Acta 446:277–283CrossRefGoogle Scholar
  36. 36.
    Levrat A, Gros A, Rugeri L et al (2008) Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth 100:792–797CrossRefGoogle Scholar
  37. 37.
    Lier H, Vorweg M, Hanke A, Görlinger K (2013) Thromboelastometry guided therapy of severe bleeding. Essener Runde algorithm. Hamostaseologie 33:51–61CrossRefGoogle Scholar
  38. 38.
    Maegele M, Inaba K, Rizoli S et al (2015) Frühe viskoelastizitätsbasierte Gerinnungstherapie bei blutenden Schwerverletzten. Bericht der Konsensusgruppe über die Konsensuskonferenz 2014 zur Erarbeitung einer S2k-Leitlinie. Anaesthesist 64:778–794CrossRefGoogle Scholar
  39. 39.
    Mallaiah S, Barclay P, Harrod I et al (2015) Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage. Anaesthesia 70:166–175CrossRefGoogle Scholar
  40. 40.
    Meyer ASP, Meyer MAS, Sørensen AM et al (2014) Thromboelastography and rotational thromboelastometry early amplitudes in 182 trauma patients with clinical suspicion of severe injury. J Trauma Acute Care Surg 76:682–690CrossRefGoogle Scholar
  41. 41.
    Mittermayr M, Velik-Salchner C, Stalzer B et al (2009) Detection of protamine and heparin after termination of cardiopulmonary bypass by thromboelastometry (ROTEM): results of a pilot study. Anesth Analg 108:743–750CrossRefGoogle Scholar
  42. 42.
    Nakayama Y, Nakajima Y, Tanaka KA et al (2015) Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery. Br J Anaesth 114:91–102CrossRefGoogle Scholar
  43. 43.
    Olde Engberink RH, Kuiper GJ, Wetzels RJ et al (2014) Rapid and correct prediction of thrombocytopenia and hypofibrinogenemia with rotational thromboelastometry in cardiac surgery. J Cardiothorac Vasc Anesth 28:210–216CrossRefGoogle Scholar
  44. 44.
    Oswald E, Velik-Salchner C, Innerhofer P et al (2015) Results of rotational thromboelastometry, coagulation activation markers and thrombin generation assays in orthopedic patients during thromboprophylaxis with rivaroxaban and enoxaparin: a prospective cohort study. Blood Coagul Fibrinolysis 26:136–144CrossRefGoogle Scholar
  45. 45.
    Paniccia R, Priora R, Liotta AA et al (2015) Platelet function tests: a comparative review. Vasc Health Risk Manag 11:133–148CrossRefGoogle Scholar
  46. 46.
    Park MS (2009) Thromboelastography as a better indicator of postinjury hypercoagulable state than prothrombin time or activated partial thromboplastin time. J Trauma 67:266–276CrossRefGoogle Scholar
  47. 47.
    Raza I, Davenport R, Rourke C et al (2013) The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost 11:307–314CrossRefGoogle Scholar
  48. 48.
    Roullet S, Freyburger G, Cruc M et al (2015) Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry-based algorithm. Liver Transpl 21:169–179CrossRefGoogle Scholar
  49. 49.
    Sangkhathat S, Suwannarat D, Boonpipattanapong T et al (2015) Rotational thromboelastometry in the diagnosis of coagulopathy in major pediatric surgical operations. J Pediatr Surg 50:2001–2004CrossRefGoogle Scholar
  50. 50.
    Schaden E, Schober A, Hacker S et al (2013) Ecarin modified rotational thrombelastometry: a point-of-care applicable alternative to monitor the direct thrombin inhibitor argatroban. Wien Klin Wochenschr 125:156–159CrossRefGoogle Scholar
  51. 51.
    Schneider T, Siegemund T, Siegemund R et al (2015) Thrombin generation and rotational thromboelastometry in the healthy adult population. Hamostaseologie 35:181–186CrossRefGoogle Scholar
  52. 52.
    Schöchl H, Fritsch T, Pavelka M et al (2009) Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thromboelastometry. J Trauma 67:125–131CrossRefGoogle Scholar
  53. 53.
    Schöchl H, Nienaber U, Hofer G et al (2010) Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM®)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 14:R55CrossRefGoogle Scholar
  54. 54.
    Schöchl H, Maegele M, Solomon C et al (2012) Early and individualized goal-directed therapy for trauma-induced coagulopathy. Scand J Trauma Resusc Emerg Med 20:15CrossRefGoogle Scholar
  55. 55.
    Schöchl H, Schlimp CJ, Voelckel W (2014) Gerinnungsmanagement bei Polytrauma mit Hilfe viskoelastischer Tests. Unfallchirurg 117:111–117CrossRefGoogle Scholar
  56. 56.
    Schöchl H, Voelckel W, Grassetto A et al (2013) Practical application of point-of-care coagulation testing to guide treatment decisions in trauma. J Trauma Acute Care Surg 74:1587–1598CrossRefGoogle Scholar
  57. 57.
    Schöchl H, Voelckel W, Maegele M et al (2014) Endogenous thrombin potential following hemostatic therapy with 4‑factor prothrombin complex concentrate: a 7‑day observational study of trauma patients. Crit Care 18:R147CrossRefGoogle Scholar
  58. 58.
    Sniecinski RM, Levy JH (2011) Bleeding and management of coagulopathy. J Thorac Cardiovasc Surg 142:662–667CrossRefGoogle Scholar
  59. 59.
    Solomon C, Ranucci M, Hochleitner G et al (2015) Assessing the methodology for calculating platelet contribution to clot strength (platelet component) in thromboelastometry and thrombelastography. Anesth Analg 121:868–878CrossRefGoogle Scholar
  60. 60.
    Solomon C, Schöchl H, Ranucci M et al (2015) Can the viscoelastic parameter α‑angle distinguish fibrinogen from platelet deficiency and guide fibrinogen supplementation? Anesth Analg 121:289–301CrossRefGoogle Scholar
  61. 61.
    Song JG, Jeong SM, Jun IG et al (2014) Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation. Br J Anaesth 112:290–297CrossRefGoogle Scholar
  62. 62.
    Spahn DR, Bouillon B, Cerny V et al (2013) Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care 17:R76CrossRefGoogle Scholar
  63. 63.
    Sucker C, Zotz RB, Görlinger K et al (2008) Rotational thrombelastometry for the bedside monitoring of recombinant hirudin. Acta Anaesthesiol Scand 52:358–362CrossRefGoogle Scholar
  64. 64.
    Tanaka KA, Bader SO, Görlinger K (2014) Novel approaches in management of perioperative coagulopathy. Curr Opin Anaesthesiol 27:72–80CrossRefGoogle Scholar
  65. 65.
    Tarzia V, Bortolussi G, Buratto E et al (2015) Single vs double antiplatelet therapy in acute coronary syndrome: predictors of bleeding after coronary artery bypass grafting. World J Cardiol 7:571–578CrossRefGoogle Scholar
  66. 66.
    Wang SC, Shieh JF, Chang KY et al (2010) Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc 42:2590–2593CrossRefGoogle Scholar
  67. 67.
    Weber CF, Görlinger K, Meininger D et al (2012) A prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology 117:531–547CrossRefGoogle Scholar
  68. 68.
    Weber CF, Sanders JO, Friedrich K et al (2011) Role of thromboelastometry for the monitoring of factor XIII. A prospective observational study in neurosurgical patients. Hamostaseologie 31:111–117CrossRefGoogle Scholar
  69. 69.
    Whiting D, DiNardo JA (2014) TEG and ROTEM: technology and clinical applications. Am J Hematol 89:228–232CrossRefGoogle Scholar
  70. 70.
    Whiting P, Al M, Westwood M et al (2015) 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 19:1–228CrossRefGoogle Scholar
  71. 71.
    Zipperle J, Schlimp CJ, Holnthoner W et al (2013) A novel coagulation assay incorporating adherent endothelial cells in thromboelastometry. Thromb Haemost 109:869–877CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Klinik für AnästhesiologieUniversitätsklinikum RWTH AachenAachenDeutschland

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