Advertisement

Whole Blood Assay: Thromboelastometry

  • Klaus GörlingerEmail author
  • Jameel Iqbal
  • Daniel Dirkmann
  • Kenichi A. Tanaka
Chapter

Abstract

Thromboelastometry (ROTEM®) is an advancement of the classical thrombelastography (TEG), first described by Hellmut Hartert in 1948. Since then, several technical enhancements made the device more robust and user-friendly, reduced intra- and inter-operator variability, and improved the diagnostic performance. Since coagulation factor concentrates such as fibrinogen concentrate and prothrombin complex concentrates (PCCs) are licensed for bleeding management due to hereditary and acquired coagulation factor deficiencies in Germany for more than 20 years, the ROTEM® delta device and assays have been designed to identify specific coagulopathies in real time and to guide hemostatic therapy most specifically with coagulation factor concentrates (e.g., fibrinogen concentrate, PCCs, factor XIII concentrate, and recombinant activated factor VII) and other blood products (e.g., fresh frozen plasma, cryoprecipitate, and platelets). The combination of specific ROTEM® assays improves the diagnostic performance significantly. The “blind spot” of viscoelastic testing—platelet dysfunction due to antiplatelet drugs or other clinical conditions such as trauma, cardiopulmonary bypass, and sepsis—could be covered by the ROTEM® platelet module using the well-established whole blood impedance aggregometry technology. As an essential part of a “patient blood management” program, the concept of thromboelastometry-guided bleeding management aims to stop bleeding as soon as possible and to avoid any unnecessary or inappropriate blood transfusion, which is known to be associated with severe adverse events. Accordingly, the implementation of thromboelastometry-guided bleeding management algorithms (“theragnostic approach”) has been shown to reduce transfusion requirements, transfusion-associated adverse events, patient’s morbidity and mortality, as well as hospital costs in several clinical settings. This concept is also gaining acceptance and recommendation in the USA, e.g., in the recently published “practice guidelines for perioperative blood management” from the “ASA Task Force on Perioperative Blood Management.” The characteristics of thromboelastometry allows for using the device at the bedside in the emergency department, the operating room, and the intensive care unit in a mobile way and in a multiuser environment, even in military settings. This could be further optimized by developing a fully automated thromboelastometry device, the ROTEM® sigma, which is a cartridge-based system with lyophilized reagent beads not requiring pipetting but still using the proven pin-and-cup technology.

Keywords

Point-of-care testing Thromboelastometry Viscoelastic testing Impedance aggregometry Platelet function analysis Bleeding management Hemostasis Coagulopathy Blood transfusion Algorithms 

References

  1. 1.
    Hartert H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wschr. 1948;26(37/38):577–83.PubMedCrossRefGoogle Scholar
  2. 2.
    Calatzis A, Fritzsche P, Calatzis A, Kling M, Hipp R, Sternberger A. A comparison of the technical principle of the ROTEG coagulation analyser and conventional thrombelastographic systems. Ann Hematol. 1996;72(1 Suppl):90.Google Scholar
  3. 3.
    Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014;89(2):228–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Espinosa A, Seghatchian J. What is happening? The evolving role of the blood bank in the management of the bleeding patient: The impact of TEG as an early diagnostic predictor for bleeding. Transfus Apher Sci. 2014;51(3):105–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Doran CM, Woolley T, Midwinter MJ. Feasibility of using rotational thromboelastometry to assess coagulation status of combat casualties in a deployed setting. J Trauma. 2010;69 Suppl 1:S40–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Woolley T, Midwinter M, Spencer P, Watts S, Doran C, Kirkman E. Utility of interim ROTEM() values of clot strength, A5 and A10, in predicting final assessment of coagulation status in severely injured battle patients. Injury. 2013;44(5):593–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Anderson L, Quasim I, Steven M, Moise SF, Shelley B, Schraag S, Sinclair A. Interoperator and intraoperator variability of whole blood coagulation assays: A comparison of thromboelastography and rotational thromboelastometry. J Cardiothorac Vasc Anesth. 2014;28(6):1550–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Saner FH, Tanaka KA, Sakai T. Viscoelastic testing in liver transplantation: TEG versus ROTEM. ILTS Education Anesthesia/CCM. 2015. http://02cb04f.netsolhost.com/cgi-bin/index.cgi?table=57&rid=4228&submenu=main&mode=222&us=&pw.
  9. 9.
    Görlinger K, Dirkmann D, Hanke AA, Kamler M, Kottenberg E, Thielmann M, Jakob H, Peters J. First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. Anesthesiology. 2011;115(6):1179–91.PubMedGoogle Scholar
  10. 10.
    Tanaka KA, Bolliger D, Vadlamudi R, Nimmo A. Rotational thromboelastometry (ROTEM)-based coagulation management in cardiac surgery and major trauma. J Cardiothorac Vasc Anesth. 2012;26(6):1083–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Dirkmann D, Görlinger K, Dusse F, Kottenberg E, Peters J. Early thromboelastometric variables reliably predict maximum clot firmness in patients undergoing cardiac surgery: a step towards earlier decision making. Acta Anaesthesiol Scand. 2013;57(5):594–603.PubMedCrossRefGoogle Scholar
  12. 12.
    Gronchi F, Perret A, Ferrari E, Marcucci CM, Flèche J, Crosset M, Schoettker P, Marcucci C. Validation of rotational thromboelastometry during cardiopulmonary bypass: A prospective, observational in-vivo study. Eur J Anaesthesiol. 2014;31(2):68–75.PubMedCrossRefGoogle Scholar
  13. 13.
    Olde Engberink RH, Kuiper GJ, Wetzels RJ, Nelemans PJ, Lance MD, Beckers EA, Henskens YM. Rapid and correct prediction of thrombocytopenia and hypofibrinogenemia with rotational thromboelastometry in cardiac surgery. J Cardiothorac Vasc Anesth. 2014;28(2):210–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Ortmann E, Rubino A, Altemimi B, Collier T, Besser MW, Klein AA. Validation of viscoelastic coagulation tests during cardiopulmonary bypass. J Thromb Haemost. 2015;13(7):1207–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Mace H, Lightfoot N, McCluskey S, Selby R, Roy D, Timoumi T, Karkouti K. Validity of thromboelastometry for rapid assessment of fibrinogen levels in heparinized samples during cardiac surgery: A retrospective, single-center, observational study. J Cardiothorac Vasc Anesth. 2016;30(1):90–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Dunham CM, Rabel C, Hileman BM, Schiraldi J, Chance EA, Shima MT, Molinar AA, Hoffman DA. TEG and RapidTEG are unreliable for detecting warfarin-coagulopathy: a prospective cohort study. Thromb J. 2014;12(1):4.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Schmidt DE, Holmström M, Majeed A, Näslin D, Wallén H, Ågren A. Detection of elevated INR by thromboelastometry and thromboelastography in warfarin treated patients and healthy controls. Thromb Res. 2015;135(5):1007–11.PubMedCrossRefGoogle Scholar
  18. 18.
    Blasi A, Muñoz G, de Soto I, Mellado R, Taura P, Rios J, Balust J, Beltran J. Reliability of thromboelastometry for detecting the safe coagulation threshold in patients taking acenocoumarol after elective heart valve replacement. Thromb Res. 2015;136(3):669–72.PubMedCrossRefGoogle Scholar
  19. 19.
    Schöchl H, Maegele M, Solomon C, Görlinger K, Voelckel W. Early and individualized goal-directed therapy for trauma-induced coagulopathy. Scand J Trauma Resusc Emerg Med. 2012;20:15.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Görlinger K, Fries D, Dirkmann D, Weber CF, Hanke AA, Schöchl H. Reduction of fresh frozen plasma requirements by perioperative point-of-care coagulation management with early calculated goal-directed therapy. Transfus Med Hemother. 2012;39(2):104–13.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Tanaka KA, Bader SO, Görlinger K. Novel approaches in management of perioperative coagulopathy. Curr Opin Anaesthesiol. 2014;27(1):72–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Tanaka KA, Mazzeffi M, Durila M. Role of prothrombin complex concentrate in perioperative coagulation therapy. J Intensive Care. 2014;2(1):60.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Inaba K, Rizoli S, Veigas PV, Callum J, Davenport R, Hess J. Maegele M; Viscoelastic Testing in Trauma Consensus Panel. 2014 Consensus conference on viscoelastic test-based transfusion guidelines for early trauma resuscitation: Report of the panel. J Trauma Acute Care Surg. 2015;78(6):1220–9. doi: 10.1097/TA.00000000000657.PubMedCrossRefGoogle Scholar
  24. 24.
    Haas T, Spielmann N, Mauch J, Madjdpour C, Speer O, Schmugge M, Weiss M. Comparison of thromboelastometry (ROTEM) with standard plasmatic coagulation testing in paediatric surgery. Br J Anaesth. 2012;108(1):36–41.PubMedCrossRefGoogle Scholar
  25. 25.
    Tanaka KA, Bader SO, Sturgil EL. Diagnosis of perioperative coagulopathy - plasma versus whole blood testing. J Cardiothorac Vasc Anesth. 2013;27(4 Suppl):S9–15.PubMedCrossRefGoogle Scholar
  26. 26.
    Görlinger K, Dirkmann D, Solomon C, Hanke AA. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability. Br J Anaesth. 2013;110(2):222–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Song JG, Jeong SM, Jun IG, Lee HM, Hwang GS. Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation. Br J Anaesth. 2014;112(2):290–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Dirkmann D, Görlinger K, Peters J. Assessment of early thromboelastometric variables from extrinsically activated assays with and without aprotinin for rapid detection of fibrinolysis. Anesth Analg. 2014;119(3):533–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Larsen OH, Fenger-Eriksen C, Christiansen K, Ingerslev J, Sørensen B. Diagnostic performance and therapeutic consequence of thromboelastometry activated by kaolin versus a panel of specific reagents. Anesthesiology. 2011;115(2):294–302.PubMedCrossRefGoogle Scholar
  30. 30.
    Solomon C, Sørensen B, Hochleitner G, Kashuk J, Ranucci M, Schöchl H. Comparison of whole blood fibrin-based clot tests in thrombelastography and thromboelastometry. Anesth Analg. 2012;114(4):721–30.PubMedCrossRefGoogle Scholar
  31. 31.
    Solomon C, Schöchl H, Ranucci M, Schlimp CJ. Can the viscoelastic parameter α-angle distinguish fibrinogen from platelet deficiency and guide fibrinogen supplementation? Anesth Analg. 2015;121(2):289–301.PubMedCrossRefGoogle Scholar
  32. 32.
    Da Luz LT, Nascimento B, Shankarakutty AK, Rizoli S, Adhikari NK. Effect of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review. Crit Care. 2014;18(5):518.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Hagemo JS, Christiaans SC, Stanworth SJ, Brohi K, Johansson PI, Goslings JC, Naess PA, Gaarder C. Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. Crit Care. 2015;19:97.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Görlinger K, Dirkmann D, Hanke AA. Potential value of transfusion protocols in cardiac surgery. Curr Opin Anaesthesiol. 2013;26(2):230–43.PubMedCrossRefGoogle Scholar
  35. 35.
    Karon BS, Tolan NV, Koch CD, Wockenfus AM, Miller RS, Lingineni RK, Pruthi RK, Chen D, Jaffe AS. Precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet agent therapy. Clin Chem. 2014;60(12):1524–31.PubMedCrossRefGoogle Scholar
  36. 36.
    Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag. 2015;11:133–48.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Petricevic M, Biocina B, Milicic D, Rotim C, Boban M. Platelet function testing and prediction of bleeding in patients exposed to clopidogrel undergoing coronary artery surgery. Clin Cardiol. 2015;38(7):443–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Corredor C, Wasowicz M, Karkouti K, Sharma V. The role of point-of-care platelet function testing in predicting postoperative bleeding following cardiac surgery: a systematic review and meta-analysis. Anaesthesia. 2015;70(6):715–31.PubMedCrossRefGoogle Scholar
  39. 39.
    Chapman MP, Moore EE, Moore HB, Gonzalez E, Morton AP, Silliman CC, Saunaia A, Banerjee A. Early TRAP pathway platelet inhibition predicts coagulopathic hemorrhage in trauma. Shock. 2015;43(6 Suppl 1):33.Google Scholar
  40. 40.
    Rahe-Meyer N, Solomon C, Vorweg M, Becker S, Stenger K, Winterhalter M, Lang T. Multicentric comparison of single portion reagents and liquid reagents for thromboelastometry. Blood Coagul Fibrinolysis. 2009;20(3):218–22.PubMedCrossRefGoogle Scholar
  41. 41.
    Lang T, Toller W, Gütl M, Mahla E, Metzler H, Rehak P, März W, Halwachs-Baumann G. Different effects of abciximab and cytochalasin D on clot strength in thrombelastography. J Thromb Haemost. 2004;2(1):147–53.PubMedCrossRefGoogle Scholar
  42. 42.
    Katori N, Tanaka KA, Szlam F, Levy JH. The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography. Anesth Analg. 2005;100(6):1781–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Weber CF, Jambor C, Marquardt M, Görlinger K, Zwissler B. Thrombelastometric detection of factor XIII deficiency. Anaesthesist. 2008;57(5):487–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Görlinger K, Bergmann L, Dirkmann D. Coagulation management in patients undergoing mechanical circulatory support. Best Pract Res Clin Anaesthesiol. 2012;26(2):179–98.PubMedCrossRefGoogle Scholar
  45. 45.
    Dirkmann D, Görlinger K, Gisbertz C, Dusse F, Peters J. Factor XIII and tranexamic acid but not recombinant factor VIIa attenuate tissue plasminogen activator-induced hyperfibrinolysis in human whole blood. Anesth Analg. 2012;114(6):1182–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Harr JN, Moore EE, Chin TL, Chapman MP, Ghasabyan A, Stringham JR, Banerjee A, Silliman CC. Viscoelastic hemostatic fibrinogen assays detect fibrinolysis early. Eur J Trauma Emerg Surg. 2015;41(1):49–56.PubMedCrossRefGoogle Scholar
  47. 47.
    Abuelkasem E, Tanaka K, Lu SY, Planinsic R, Sakai T. FIBTEM is more sensitive than EXTEM and Kaolin-TEG in detecting fibrinolysis: Part II of a prospective comparative study between ROTEM vs. TEG in liver transplantation. ASA Abstract A1046, October 24, 2015. http://www.asaabstracts.com/strands/asaabstracts/printAbstract.htm;jsessionid=E33CA753FC7B6CD93B86D48A72B1AA3F?index=2&year=2015&absnum=2748&type=session
  48. 48.
    Koster A, Börgermann J, Gummert J, Rudloff M, Zittermann A, Schirmer U. 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. 2014;20(3):290–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Yamamoto T, Wolf HG, Sinzobahamvya N, Asfour B, Hraska V, Schindler E. Prolonged activated clotting time after protamine administration does not indicate residual heparinization after cardiopulmonary bypass in pediatric open heart surgery. Thorac Cardiovasc Surg. 2015;63(5):397–403.PubMedCrossRefGoogle Scholar
  50. 50.
    Sucker C, Zotz RB, Görlinger K, Hartmann M. Rotational thrombelastometry for the bedside monitoring of recombinant hirudin. Acta Anaesthesiol Scand. 2008;52(3):358–62.PubMedCrossRefGoogle Scholar
  51. 51.
    Schaden E, Schober A, Hacker S, Kozek-Langenecker S. Ecarin modified rotational thrombelastometry: a point-of-care applicable alternative to monitor the direct thrombin inhibitor argatroban. Wien Klin Wochenschr. 2013;125(5-6):156–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Adamzik M, Eggmann M, Frey UH, Görlinger K, Bröcker-Preuss M, Marggraf G, Saner F, Eggebrecht H, Peters J, Hartmann M. Comparison of thromboelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critically ill adults. Crit Care. 2010;14(5):R178.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Adamzik M, Schäfer S, Frey UH, Becker A, Kreuzer M, Winning S, Frede S, Steinmann J, Fandrey J, Zacharowski K, Siffert W, Peters J, Hartmann M. The NFKB1 promoter polymorphism (-94ins/delATTG) alters nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation and is associated with increased mortality in sepsis. Anesthesiology. 2013;118(1):123–33.PubMedCrossRefGoogle Scholar
  54. 54.
    Müller MC, Meijers JC, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014;18(1):R30.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    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):551–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Görlinger K, Jambor C, Hanke AA, Dirkmann D, Adamzik M, Hartmann M, Rahe-Meyer N. Perioperative coagulation management and control of platelet transfusion by point-of-care platelet function analysis. Transfus Med Hemother. 2007;34(6):396–411.CrossRefGoogle Scholar
  57. 57.
    Tem Innnovations GmbH. ROTEM delta Manual 2.2.0.01. EN 2012.Google Scholar
  58. 58.
    Lang T, Bauters A, Braun SL, Pötzsch B, von Pape KW, Kolde HJ, Lakner M. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis. 2005;16(4):301–10.PubMedCrossRefGoogle Scholar
  59. 59.
    Oswald E, Stalzer B, Heitz E, Weiss M, Schmugge M, Strasak A, Innerhofer P, Haas T. Thromboelastometry (ROTEM) in children: age-related reference ranges and correlations with standard coagulation tests. Br J Anaesth. 2010;105(6):827–35.PubMedCrossRefGoogle Scholar
  60. 60.
    Huissoud C, Carrabin N, Benchaib M, Fontaine O, Levrat A, Massignon D, Touzet S, Rudigoz RC, Berland M. Coagulation assessment by rotation thrombelastometry in normal pregnancy. Thromb Haemost. 2009;101(4):755–61.PubMedGoogle Scholar
  61. 61.
    Oudghiri M, Keita H, Kouamou E, Boutonnet M, Orsini M, Desconclois C, Mandelbrot L, Daures JP, Stépanian A, Peynaud-Debayle E, de Prost D. Reference values for rotation thromboelastometry (ROTEM) parameters following non-haemorrhagic deliveries. Correlations with standard haemostasis parameters. Thromb Haemost. 2011;106(1):176–8.PubMedCrossRefGoogle Scholar
  62. 62.
    de Lange NM, van Rheenen-Flach LE, Lancé MD, Mooyman L, Woiski M, van Pampus EC, Porath M, Bolte AC, Smits L, Henskens YM, Scheepers HC. Peri-partum reference ranges for ROTEM(R) thromboelastometry. Br J Anaesth. 2014;112(5):852–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Koami H, Sakamoto Y, Ohta M, Goto A, Narumi S, Imahase H, Yahata M, Miike T, Iwamura T, Yamada KC, Inoue S. Can the rotational thromboelastometry predict the septic disseminated intravascular coagulation? Blood Coagul Fibrinolysis. 2015;26(7):778–83.PubMedGoogle Scholar
  64. 64.
    Stanworth SJ, Grant-Casey J, Lowe D, Laffan M, New H, Murphy MF, Allard S. The use of fresh-frozen plasma in England: high levels of inappropriate use in adults and children. Transfusion. 2011;51(1):62–70.PubMedCrossRefGoogle Scholar
  65. 65.
    Tinmouth A, Thompson T, Arnold DM, Callum JL, Gagliardi K, Lauzon D, Owens W, Pinkerton P. Utilization of frozen plasma in Ontario: a provincewide audit reveals a high rate of inappropriate transfusions. Transfusion. 2013;53(10):2222–9.PubMedGoogle Scholar
  66. 66.
    Tripodi A, Primignani M, Chantarangkul V, Viscardi Y, Dell’Era A, Fabris FM, Mannucci PM. The coagulopathy of cirrhosis assessed by thromboelastometry and its correlation with conventional coagulation parameters. Thromb Res. 2009;124(1):132–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Bedreli S, Sowa JP, Gerken G, Saner FH, Canbay A. Management of acute-on-chronic liver failure: rotational thromboelastometry may reduce substitution of coagulation factors in liver cirrhosis. Gut. 2016;65(2):357–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Durila M, Lukáš P, Astraverkhava M, Beroušek J, Zábrodský M, Vymazal T. Tracheostomy in intensive care unit patients can be performed without bleeding complications in case of normal thromboelastometry results (EXTEM CT) despite increased PT-INR: a prospective pilot study. BMC Anesthesiol. 2015;15:89.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Görlinger K, Saner FH. Prophylactic plasma and platelet transfusion in the critically Ill patient: just useless and expensive or even harmful? BMC Anesthesiol. 2015;15(1):86.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Rourke C, Curry N, Khan S, Taylor R, Raza I, Davenport R, Stanworth S, Brohi K. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10(7):1342–51.PubMedCrossRefGoogle Scholar
  71. 71.
    Flisberg P, Rundgren M, Engström M. The effects of platelet transfusions evaluated using rotational thromboelastometry. Anesth Analg. 2009;108(5):1430–2.PubMedCrossRefGoogle Scholar
  72. 72.
    Greene LA, Chen S, Seery C, Imahiyerobo AM, Bussel JB. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol. 2014;166(4):592–600.PubMedCrossRefGoogle Scholar
  73. 73.
    Fayed NA, Abdallah AR, Khalil MK, Marwan IK. Therapeutic rather than prophylactic platelet transfusion policy for severe thrombocytopenia during liver transplantation. Platelets. 2014;25(8):576–86.PubMedCrossRefGoogle Scholar
  74. 74.
    Kander T, Tanaka KA, Norström E, Persson J, Schött U. The effect and duration of prophylactic platelet transfusions before insertion of a central venous catheter in patients with bone marrow failure evaluated with point-of-care methods and flow cytometry. Anesth Analg. 2014;119(4):882–90.PubMedCrossRefGoogle Scholar
  75. 75.
    Davenport R, Manson J, De’Ath H, Platton S, Coates A, Allard S, Hart D, Pearse R, Pasi KJ, MacCallum P, Stanworth S, Brohi K. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med. 2011;39(12):2652–8.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Dekker SE, Viersen VA, Duvekot A, de Jong M, van den Brom CE, van de Ven PM, Schober P, Boer C. Lysis onset time as diagnostic rotational thromboelastometry parameter for fast detection of hyperfibrinolysis. Anesthesiology. 2014;121(1):89–97.PubMedCrossRefGoogle Scholar
  77. 77.
    Chapman MP, Moore EE, Ramos CR, Ghasabyan A, Harr JN, Chin TL, Stringham JR, Sauaia A, Silliman CC, Banerjee A. Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy. J Trauma Acute Care Surg. 2013;75(6):961–7. discussion 967.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Moore HB, Moore EE, Gonzalez E, Chapman MP, Chin TL, Silliman CC, Banerjee A, Sauaia A. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy. J Trauma Acute Care Surg. 2014;77(6):811–7.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Meltzer ME, Lisman T, de Groot PG, Meijers JC, le Cessie S, Doggen CJ, Rosendaal FR. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood. 2010;116(1):113–21.PubMedCrossRefGoogle Scholar
  80. 80.
    Meltzer ME, Doggen CJ, de Groot PG, Rosendaal FR, Lisman T. Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men. Blood. 2010;116(4):529–36.PubMedCrossRefGoogle Scholar
  81. 81.
    Wada T, Gando S, Mizugaki A, Yanagida Y, Jesmin S, Yokota H, Ieko M. Coagulofibrinolytic changes in patients with disseminated intravascular coagulation associated with post-cardiac arrest syndrome - fibrinolytic shutdown and insufficient activation of fibrinolysis lead to organ dysfunction. Thromb Res. 2013;132(1):e64–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Kalb ML, Potura L, Scharbert G, Kozek-Langenecker SA. The effect of ex vivo anticoagulants on whole blood platelet aggregation. Platelets. 2009;20(1):7–11. doi: 10.1080/09537100802364076.PubMedCrossRefGoogle Scholar
  83. 83.
    Kaiser AF, Neubauer H, Franken CC, Krüger JC, Mügge A, Meves SH. Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions. Platelets. 2012;23(5):359–67.PubMedCrossRefGoogle Scholar
  84. 84.
    Johnston LR, Larsen PD, La Flamme AC, Harding SA. Methodological considerations for the assessment of ADP induced platelet aggregation using the Multiplate analyser. Platelets. 2013;24(4):303–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Glas M, Mauer D, Kassas H, Volk T, Kreuer S. Sample transport by pneumatic tube system alters results of multiple electrode aggregometry but not rotational thromboelastometry. Platelets. 2013;24(6):454–61.PubMedCrossRefGoogle Scholar
  86. 86.
    Lang T, Tollnick M, Rieke M. Evaluation of the new device ROTEM platelet. Abstract, GTH 2014, Vienna, Austria, Feb. 12-15, 2014.Google Scholar
  87. 87.
    Goerlinger K, Neble S, Lange-Clary G, Campbell K, Lakner M. Evaluation of the diagnostic performance of the ROTEM platelet assay ADPTEM to detect patients on clopidogrel. ASA Abstract A2174, October 25, 2015. http://www.asaabstracts.com/strands/asaabstracts/abstract.htm;jsessionid=4EB2D2DB42292072E0C0641867ADF65F?year=2015&index=8&absnum=3252
  88. 88.
    Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schömig A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009;53(10):849–56.PubMedCrossRefGoogle Scholar
  89. 89.
    Sibbing D, Schulz S, Braun S, Morath T, Stegherr J, Mehilli J, Schömig A, von Beckerath N, Kastrati A. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost. 2010;8(2):250–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Rahe-Meyer N, Winterhalter M, Boden A, Froemke C, Piepenbrock S, Calatzis A, Solomon C. Platelet concentrates transfusion in cardiac surgery and platelet function assessment by multiple electrode aggregometry. Acta Anaesthesiol Scand. 2009;53(2):168–75.PubMedCrossRefGoogle Scholar
  91. 91.
    Ranucci M, Baryshnikova E, Soro G, Ballotta A, De Benedetti D. Conti D; Surgical and Clinical Outcome Research (SCORE) Group. Multiple electrode whole-blood aggregometry and bleeding in cardiac surgery patients receiving thienopyridines. Ann Thorac Surg. 2011;91(1):123–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Ranucci M, Colella D, Baryshnikova E. Di Dedda U; Surgical and Clinical Outcome Research (SCORE) Group. Effect of preoperative P2Y12 and thrombin platelet receptor inhibition on bleeding after cardiac surgery. Br J Anaesth. 2014;113(6):970–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Solomon C, Traintinger S, Ziegler B, Hanke A, Rahe-Meyer N, Voelckel W, Schöchl H. Platelet function following trauma. A multiple electrode aggregometry study. Thromb Haemost. 2011;106(2):322–30.PubMedCrossRefGoogle Scholar
  94. 94.
    Kutcher ME, Redick BJ, McCreery RC, Crane IM, Greenberg MD, Cachola LM, Nelson MF, Cohen MJ. Characterization of platelet dysfunction after trauma. J Trauma Acute Care Surg. 2012;73(1):13–9.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Adamzik M, Görlinger K, Peters J, Hartmann M. Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis. Crit Care. 2012;16(5):R204.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Petricevic M, Biocina B, Milicic D, Konosic S, Svetina L, Lekić A, Zdilar B, Burcar I, Milosevic M, Brahimaj R, Samardzic J, Gasparovic H. Bleeding risk assessment using whole blood impedance aggregometry and rotational thromboelastometry in patients following cardiac surgery. J Thromb Thrombolysis. 2013;36(4):514–26.PubMedCrossRefGoogle Scholar
  97. 97.
    Romlin BS, Söderlund F, Wåhlander H, Nilsson B, Baghaei F, Jeppsson A. Platelet count and function in paediatric cardiac surgery: a prospective observational study. Br J Anaesth. 2014;113(5):847–54.PubMedCrossRefGoogle Scholar
  98. 98.
    Petricevic M, Milicic D, White A, Boban M, Mihaljevic MZ, Piljic D, Rotim A, Buca A, Mihalj M, Biocina B. Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery. J Thromb Thrombolysis. 2015;40(3):383–91.PubMedCrossRefGoogle Scholar
  99. 99.
    Weber CF, Dietrich W, Spannagl M, Hofstetter C, Jámbor C. A point-of-care assessment of the effects of desmopressin on impaired platelet function using multiple electrode whole-blood aggregometry in patients after cardiac surgery. Anesth Analg. 2010;110(3):702–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Weber CF, Görlinger K, Byhahn C, Moritz A, Hanke AA, Zacharowski K, Meininger D. Tranexamic acid partially improves platelet function in patients treated with dual antiplatelet therapy. Eur J Anaesthesiol. 2011;28(1):57–62. doi: 10.1097/EJA.0b013e32834050ab.PubMedCrossRefGoogle Scholar
  101. 101.
    Cammerer U, Dietrich W, Rampf T, Braun SL, Richter JA. The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg. 2003;96(1):51–7.PubMedGoogle Scholar
  102. 102.
    Davidson SJ, McGrowder D, Roughton M, Kelleher AA. Can ROTEM thromboelastometry predict postoperative bleeding after cardiac surgery? J Cardiothorac Vasc Anesth. 2008;22(5):655–61.PubMedCrossRefGoogle Scholar
  103. 103.
    Fayed N, Mourad W, Yassen K, Görlinger K. Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation. Transfus Med Hemother. 2015;42(2):99–108.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Schöchl H, Cotton B, Inaba K, Nienaber U, Fischer H, Voelckel W, Solomon C. FIBTEM provides early prediction of massive transfusion in trauma. Crit Care. 2011;15(6):R265.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Adamzik M, Langemeier T, Frey UH, Görlinger K, Saner F, Eggebrecht H, Peters J, Hartmann M. Comparison of thrombelastometry with simplified acute physiology score II and sequential organ failure assessment scores for the prediction of 30-day survival: a cohort study. Shock. 2011;35(4):339–42.PubMedCrossRefGoogle Scholar
  106. 106.
    Sarani B, Dunkman WJ, Dean L, Sonnad S, Rohrbach JI, Gracias VH. Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Crit Care Med. 2008;36(4):1114–8.PubMedCrossRefGoogle Scholar
  107. 107.
    Inaba K, Branco BC, Rhee P, Blackbourne LH, Holcomb JB, Teixeira PG, Shulman I, Nelson J, Demetriades D. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg. 2010;210(6):957–65.PubMedCrossRefGoogle Scholar
  108. 108.
    Theusinger OM, Stein P, Spahn DR. Transfusion strategy in multiple trauma patients. Curr Opin Crit Care. 2014;20(6):646–55.PubMedCrossRefGoogle Scholar
  109. 109.
    Maegele M, Brockamp T, Nienaber U, Probst C, Schoechl H, Görlinger K, Spinella P. Predictive models and algorithms for the need of transfusion including massive transfusion in severely injured patients. Transfus Med Hemother. 2012;39(2):85–97.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Tauber H, Innerhofer P, Breitkopf R, Westermann I, Beer R, El Attal R, Strasak A, Mittermayr M. Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma: results of the ‘Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study’. Br J Anaesth. 2011;107(3):378–87.PubMedCrossRefGoogle Scholar
  111. 111.
    Reinhöfer M, Brauer M, Franke U, Barz D, Marx G, Lösche W. The value of rotation thromboelastometry to monitor disturbed perioperative haemostasis and bleeding risk in patients with cardiopulmonary bypass. Blood Coagul Fibrinolysis. 2008;19(3):212–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Petricevic M, Konosic S, Biocina B, Dirkmann D, White A, Mihaljevic MZ, Ivancan V, Konosic L, Svetina L, Görlinger K. Bleeding risk assessment in patients undergoing elective cardiac surgery using ROTEM™ platelet and Multiplate™ impedance aggregometry. (NCT02277379). Anaesthesia. 2016. doi:  10.1111/anae.13303 Google Scholar
  113. 113.
    Blasi A, Beltran J, Pereira A, Martinez-Palli G, Torrents A, Balust J, Zavala E, Taura P, Garcia-Valdecasas JC. An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation. Transfusion. 2012;52(9):1989–98.PubMedCrossRefGoogle Scholar
  114. 114.
    Collins PW, Lilley G, Bruynseels D, Laurent DB, Cannings-John R, Precious E, Hamlyn V, Sanders J, Alikhan R, Rayment R, Rees A, Kaye A, Hall JE, Paranjothy S, Weeks A, Collis RE. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood. 2014;124(11):1727–36.PubMedCrossRefGoogle Scholar
  115. 115.
    Aawar N, Alikhan R, Bruynseels D, Cannings-John R, Collis R, Dick J, Elton C, Fernando R, Hall J, Hood K, Lack N, Mallaiah S, Maybury H, Nuttall J, Paranjothy S, Rayment R, Rees A, Sanders J, Townson J, Weeks A, Collins P. Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2015;16:169.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Brenner T, Schmidt K, Delang M, Mehrabi A, Bruckner T, Lichtenstern C, Martin E, Weigand MA, Hofer S. Viscoelastic and aggregometric point-of-care testing in patients with septic shock - cross-links between inflammation and haemostasis. Acta Anaesthesiol Scand. 2012;56(10):1277–90.PubMedCrossRefGoogle Scholar
  117. 117.
    CRASH-2 Collaborators, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. 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):1096–101, 1101.e1-2.CrossRefGoogle Scholar
  118. 118.
    Weber CF, Görlinger K, Meininger D, Herrmann E, Bingold T, Moritz A, Cohn LH, Zacharowski K. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology. 2012;117(3):531–47.PubMedCrossRefGoogle Scholar
  119. 119.
    Spahn DR, Goodnough LT. Alternatives to blood transfusion. Lancet. 2013;381(9880):1855–65.PubMedCrossRefGoogle Scholar
  120. 120.
    Saner FH. Rotational thrombelastometry: a step forward to safer patient care? Crit Care. 2014;18(6):706.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Dimitrova-Karamfilova A, Patokova Y, Solarova T, Petrova I, Natchev G. Rotational thromboelastography for assessment of hypercoagulation and thrombosis in patients with cardiovascular disease. J Life Sci. 2012;6:28–35.Google Scholar
  122. 122.
    Hincker A, Feit J, Sladen RN, Wagener G. Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery. Crit Care. 2014;18(5):549.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Rossetto V, Spiezia L, Senzolo M, Rodriguez-Castro KI, Maggiolo S, Simioni P. Whole blood rotation thromboelastometry (ROTEM) profiles in subjects with non-neoplastic portal vein thrombosis. Thromb Res. 2013;132(2):e131–4.PubMedCrossRefGoogle Scholar
  124. 124.
    Campello E, Spiezia L, Zabeo E, Maggiolo S, Vettor R, Simioni P. Hypercoagulability detected by whole blood thromboelastometry (ROTEM) and impedance aggregometry (MULTIPLATE) in obese patients. Thromb Res. 2015;135(3):548–53.PubMedCrossRefGoogle Scholar
  125. 125.
    Kolbenschlag J, Daigeler A, Lauer S, Wittenberg G, Fischer S, Kapalschinski N, Lehnhardt M, Goertz O. Can rotational thromboelastometry predict thrombotic complications in reconstructive microsurgery? Microsurgery. 2014;34(4):253–60.PubMedCrossRefGoogle Scholar
  126. 126.
    Thorson CM, Van Haren RM, Ryan ML, Curia E, Sleeman D, Levi JU, Livingstone AS, Proctor KG. Pre-existing hypercoagulability in patients undergoing potentially curative cancer resection. Surgery. 2014;155(1):134–44.PubMedCrossRefGoogle Scholar
  127. 127.
    Van Haren RM, Valle EJ, Thorson CM, Guarch GA, Jouria JM, Andrews DM, Sleeman D, Levi JU, Livingstone AS, Proctor KG. Long-term coagulation changes after resection of thoracoabdominal malignancies. J Am Coll Surg. 2014;218(4):846–54.PubMedCrossRefGoogle Scholar
  128. 128.
    Treliński J, Misiewicz M, Robak M, Smolewski P, Chojnowski K. Assessment of rotation thromboelastometry (ROTEM) parameters in patients with multiple myeloma at diagnosis. Thromb Res. 2014;133(4):667–70.PubMedCrossRefGoogle Scholar
  129. 129.
    Rossetto V, Spiezia L, Senzolo M, Rodriguez-Castro KI, Gavasso S, Woodhams B, Simioni P. Does decreased fibrinolysis have a role to play in the development of non-neoplastic portal vein thrombosis in patients with hepatic cirrhosis? Intern Emerg Med. 2014;9(4):397–403.PubMedCrossRefGoogle Scholar
  130. 130.
    Prakash S, Verghese S, Roxby D, Dixon D, Bihari S, Bersten A. Changes in fibrinolysis and severity of organ failure in sepsis: a prospective observational study using point-of-care test - ROTEM. J Crit Care. 2015;30(2):264–70.PubMedCrossRefGoogle Scholar
  131. 131.
    Mosnier LO. Platelet factor 4 inhibits thrombomodulin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) by thrombin. J Biol Chem. 2011;286(1):502–10.PubMedCrossRefGoogle Scholar
  132. 132.
    Ozolina A, Strike E, Jaunalksne I, Serova J, Romanova T, Zake LN, Sabelnikovs O, Vanags I. Influence of PAI-1 gene promoter-675 (4G/5G) polymorphism on fibrinolytic activity after cardiac surgery employing cardiopulmonary bypass. Medicina (Kaunas). 2012;48(10):515–20.Google Scholar
  133. 133.
    Levrat A, Gros A, Rugeri L, Inaba K, Floccard B, Negrier C, David JS. Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth. 2008;100(6):792–7. doi: 10.1093/bja/aen083.PubMedCrossRefGoogle Scholar
  134. 134.
    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):125–31.PubMedCrossRefGoogle Scholar
  135. 135.
    Theusinger OM, Wanner GA, Emmert MY, Billeter A, Eismon J, Seifert B, Simmen HP, Spahn DR, Baulig W. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma. Anesth Analg. 2011;113(5):1003–12.PubMedCrossRefGoogle Scholar
  136. 136.
    Nardi G, Agostini V, Rondinelli B, Russo E, Bastianini B, Bini G, Bulgarelli S, Cingolani E, Donato A, Gambale G, Ranaldi G. Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs. Crit Care. 2015;19:83.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011;365(2):147–56. doi: 10.1056/NEJMra1011170.PubMedCrossRefGoogle Scholar
  138. 138.
    Schaden E, Saner FH, Goerlinger K. Coagulation pattern in critical liver dysfunction. Curr Opin Crit Care. 2013;19(2):142–8.PubMedCrossRefGoogle Scholar
  139. 139.
    Ranucci M, Baryshnikova E, Castelvecchio S. Pelissero G; Surgical and Clinical Outcome Research (SCORE) Group. Major bleeding, transfusions, and anemia: the deadly triad of cardiac surgery. Ann Thorac Surg. 2013;96(2):478–85.PubMedCrossRefGoogle Scholar
  140. 140.
    Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17(2):R76.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Filipescu D, Hunt BJ, Komadina R, Maegele M, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Spahn DR. STOP Bleeding Campaign. The STOP the Bleeding Campaign. Crit Care. 2013;17(2):136.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Sibbing D, Steinhubl SR, Schulz S, Schömig A, Kastrati A. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol. 2010;56(4):317–8.PubMedCrossRefGoogle Scholar
  143. 143.
    Kozek-Langenecker SA. Coagulation and transfusion in the postoperative bleeding patient. Curr Opin Crit Care. 2014;20(4):460–6.PubMedCrossRefGoogle Scholar
  144. 144.
    Khan S, Brohi K, Chana M, Raza I, Stanworth S, Gaarder C. Davenport R; International Trauma Research Network (INTRN). Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage. J Trauma Acute Care Surg. 2014;76(3):561–8.PubMedCrossRefGoogle Scholar
  145. 145.
    Müller MC, Straat M, Meijers JC, Klinkspoor JH, de Jonge E, Arbous MS, Schultz MJ, Vroom MB, Juffermans NP. Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy. J Thromb Haemost. 2015;13(6):989–97.PubMedCrossRefGoogle Scholar
  146. 146.
    Görlinger K. Coagulation management during liver transplantation. Hamostaseologie. 2006;26(3 Suppl 1):S64–76.PubMedGoogle Scholar
  147. 147.
    Lier H, Vorweg M, Hanke A, Görlinger K. Thromboelastometry guided therapy of severe bleeding. Essener Runde algorithm. Hämostaseologie. 2013;33(1):51–61.PubMedCrossRefGoogle Scholar
  148. 148.
    Görlinger K, Dirkmann D, Weber CF, Rahe-Meyer N, Hanke AA. Algorithms for transfusion and coagulation management in massive haemorrhage. Anästh Intensivmed. 2011;52(2):145–59.Google Scholar
  149. 149.
    Schöchl H, Schlimp CJ, Voelckel W. Potential value of pharmacological protocols in trauma. Curr Opin Anaesthesiol. 2013;26(2):221–9.PubMedCrossRefGoogle Scholar
  150. 150.
    Rahe-Meyer N, Solomon C, Hanke A, Schmidt DS, Knoerzer D, Hochleitner G, Sørensen B, Hagl C, Pichlmaier M. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Anesthesiology. 2013;118(1):40–50.PubMedCrossRefGoogle Scholar
  151. 151.
    Nakayama Y, Nakajima Y, Tanaka KA, Sessler DI, Maeda S, Iida J, Ogawa S, Mizobe T. Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery. Br J Anaesth. 2015;114(1):91–102.PubMedCrossRefGoogle Scholar
  152. 152.
    Karkouti K, McCluskey SA, Callum J, Freedman J, Selby R, Timoumi T, Roy D, Rao V. Evaluation of a novel transfusion algorithm employing point-of-care coagulation assays in cardiac surgery: a retrospective cohort study with interrupted time-series analysis. Anesthesiology. 2015;122(3):560–70.PubMedCrossRefGoogle Scholar
  153. 153.
    Pearse BL, Smith I, Faulke D, Wall D, Fraser JF, Ryan EG, Drake L, Rapchuk IL, Tesar P, Ziegenfuss M, Fung YL. Protocol guided bleeding management improves cardiac surgery patient outcomes. Vox Sang. 2015;109(3):267–79.PubMedCrossRefGoogle Scholar
  154. 154.
    Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A, Surgical Clinical Outcome REsearch (SCORE) Group. Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc. 2015;4(6):e002066.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Haas T, Görlinger K, Grassetto A, Agostini V, Simioni P, Nardi G, Ranucci M. Thromboelastometry for guiding bleeding management of the critically ill patient: A systematic review of the literature. Minerva Anestesiol. 2014;80(12):1320–35.PubMedGoogle Scholar
  156. 156.
    Schöchl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, Kozek-Langenecker S, Solomon C. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care. 2010;14(2):R55.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Schöchl H, Nienaber U, Maegele M, Hochleitner G, Primavesi F, Steitz B, Arndt C, Hanke A, Voelckel W, Solomon C. Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Crit Care. 2011;15(2):R83.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Schaden E, Kimberger O, Kraincuk P, Baron DM, Metnitz PG, Kozek-Langenecker S. Perioperative treatment algorithm for bleeding burn patients reduces allogeneic blood product requirements. Br J Anaesth. 2012;109(3):376–81.PubMedCrossRefGoogle Scholar
  159. 159.
    Lendemans S, Düsing H, Assmuth S, Hußmann B, Wafaisade A, Lefering R, Görlinger K, Marzi I. Die Einführung eines spezifischen Gerinnungsprotokolls (Point of Care) verbessert das Outcome beim blutenden Schwerverletzten: eine Subgruppenanalyse von 172 Patienten unter Beteiligung des Traumaregisters DGU (gefördert durch die DIVI). Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013). Berlin, 22.-25.10.2013. Düsseldorf: German Medical Science GMS Publishing House; published Oct 23, 2013. DocWI50-561.Google Scholar
  160. 160.
    Kirchner C, Dirkmann D, Treckmann JW, Paul A, Hartmann M, Saner FH, Görlinger K. Coagulation management with factor concentrates in liver transplantation: a single-center experience. Transfusion. 2014;54(10 Pt 2):2760–8.PubMedCrossRefGoogle Scholar
  161. 161.
    Mallaiah S, Barclay P, Harrod I, Chevannes C, Bhalla A. Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage. Anaesthesia. 2015;70(2):166–75.PubMedCrossRefGoogle Scholar
  162. 162.
    Mallaiah S, Chevannes C, McNamara H, Barclay P. A reply. Anaesthesia. 2015;70(6):760–1.PubMedCrossRefGoogle Scholar
  163. 163.
    Naik BI, Pajewski TN, Bogdonoff DI, Zuo Z, Clark P, Terkawi AS, Durieux ME, Shaffrey CI, Nemergut EC. Rotational thromboelastometry-guided blood product management in major spine surgery. J Neurosurg Spine. 2015;23(2):239–49.PubMedCrossRefGoogle Scholar
  164. 164.
    Curry N, Rourke C, Davenport R, Beer S, Pankhurst L, Deary A, Thomas H, Llewelyn C, Green L, Doughty H, Nordmann G, Brohi K, Stanworth S. Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth. 2015;115(1):76–83.PubMedCrossRefGoogle Scholar
  165. 165.
    Haas T, Spielmann N, Restin T, Seifert B, Henze G, Obwegeser J, Min K, Jeszenszky D, Weiss M, Schmugge M. Higher fibrinogen concentrations for reduction of transfusion requirements during major paediatric surgery: A prospective randomised controlled trial. Br J Anaesth. 2015;115(2):234–43.PubMedCrossRefGoogle Scholar
  166. 166.
    Mittermayr M, Streif W, Haas T, Fries D, Velik-Salchner C, Klingler A, Innerhofer P. Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo. Br J Anaesth. 2008;100(3):307–14.PubMedCrossRefGoogle Scholar
  167. 167.
    Velik-Salchner C, Haas T, Innerhofer P, Streif W, Nussbaumer W, Klingler A, Klima G, Martinowitz U, Fries D. The effect of fibrinogen concentrate on thrombocytopenia. J Thromb Haemost. 2007;5(5):1019–25.PubMedCrossRefGoogle Scholar
  168. 168.
    Görlinger K, Shore-Lesserson L, Dirkmann D, Hanke AA, Rahe-Meyer N, Tanaka KA. Management of hemorrhage in cardiothoracic surgery. J Cardiothorac Vasc Anesth. 2013;27(4 Suppl):S20–34.PubMedCrossRefGoogle Scholar
  169. 169.
    Tripodi A, Primignani M, Chantarangkul V, Lemma L, Jovani M, Rebulla P, Mannucci PM. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int. 2013;33(3):362–7.PubMedCrossRefGoogle Scholar
  170. 170.
    Konkle BA. Acquired disorders of platelet function. Hematology Am Soc Hematol Educ Program. 2011;2011:391–6.PubMedGoogle Scholar
  171. 171.
    Scharf RE. Drugs that affect platelet function. Semin Thromb Hemost. 2012;38(8):865–83.PubMedCrossRefGoogle Scholar
  172. 172.
    Pereboom IT, de Boer MT, Haagsma EB, Hendriks HG, Lisman T, Porte RJ. Platelet transfusion during liver transplantation is associated with increased postoperative mortality due to acute lung injury. Anesth Analg. 2009;108(4):1083–91.PubMedCrossRefGoogle Scholar
  173. 173.
    Spiess BD. Platelet transfusions: the science behind safety, risks and appropriate applications. Best Pract Res Clin Anaesthesiol. 2010;24(1):65–83.PubMedCrossRefGoogle Scholar
  174. 174.
    Göringer K, Oprea G, Peters J, Hartmann M. Fibrinogen reverses the eptifibatide-induced decrease of maximum clot firmness but not impaired platelet aggregation. J Cardiothorac Vasc Anesth. 2010;24(Suppl3):S35.Google Scholar
  175. 175.
    Cartwright BL, Kam P, Yang K. Efficacy of fibrinogen concentrate compared with cryoprecipitate for reversal of the antiplatelet effect of clopidogrel in an in vitro model, as assessed by multiple electrode platelet aggregometry, thromboelastometry, and modified thromboelastography. J Cardiothorac Vasc Anesth. 2015;29(3):694–702.PubMedCrossRefGoogle Scholar
  176. 176.
    Vigué B, Ract C, Tremey B, Engrand N, Leblanc PE, Decaux A, Martin L, Benhamou D. Ultra-rapid management of oral anticoagulant therapy-related surgical intracranial hemorrhage. Intensive Care Med. 2007;33(4):721–5.PubMedCrossRefGoogle Scholar
  177. 177.
    Riess HB, Meier-Hellmann A, Motsch J, Elias M, Kursten FW, Dempfle CE. Prothrombin complex concentrate (Octaplex) in patients requiring immediate reversal of oral anticoagulation. Thromb Res. 2007;121(1):9–16.PubMedCrossRefGoogle Scholar
  178. 178.
    Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A. Ostermann H; Beriplex P/N Anticoagulation Reversal Study Group. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost. 2008;6(4):622–31.PubMedCrossRefGoogle Scholar
  179. 179.
    Innerhofer P, Westermann I, Tauber H, Breitkopf R, Fries D, Kastenberger T, El Attal R, Strasak A, Mittermayr M. The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma. Injury. 2013;44(2):209–16.PubMedCrossRefGoogle Scholar
  180. 180.
    American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management. Anesthesiology. 2015;122(2):241–75.CrossRefGoogle Scholar
  181. 181.
    Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation. 2013;128(4):360–4.PubMedCrossRefGoogle Scholar
  182. 182.
    Sarode R, Milling Jr TJ, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234–43.PubMedGoogle Scholar
  183. 183.
    Goldstein JN, Refaai MA, Milling Jr TJ, Lewis B, Goldberg-Alberts R, Hug BA, Sarode R. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385(9982):2077–87.PubMedCrossRefGoogle Scholar
  184. 184.
    Tazarourte K, Riou B, Tremey B, Samama CM, Vicaut E, Vigué B, EPAHK Study Group. Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study). Crit Care. 2014;18(2):R81.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Bolton-Maggs PH. Bullet points from SHOT: key messages and recommendations from the Annual SHOT Report 2013. Transfus Med. 2014;24(4):197–203.PubMedCrossRefGoogle Scholar
  186. 186.
    Refaai MA, Goldstein JN, Lee ML, Durn BL, Milling Jr TJ, Sarode R. Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. Transfusion. 2015;55(11):2722–9.PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Carvalho MC, Rodrigues AG, Conceição LM, Galvão ML, Ribeiro LC. Prothrombin complex concentrate (Octaplex): a Portuguese experience in 1152 patients. Blood Coagul Fibrinolysis. 2012;23(3):222–8.PubMedCrossRefGoogle Scholar
  188. 188.
    Hanke AA, Joch C, Görlinger K. Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study. Br J Anaesth. 2013;110(5):764–72.PubMedCrossRefGoogle Scholar
  189. 189.
    Milling TJ, Refaai MA, Goldstein JN, Schneider A, Omert L, Harman A, Lee ML, Sarode R. Thromboembolic events after vitamin K antagonist reversal with 4-factor prothrombin complex concentrate: Exploratory analyses of two randomized, plasma-controlled studies. Ann Emerg Med. 2016;67(1):96–105.e5.PubMedCrossRefGoogle Scholar
  190. 190.
    Eller T, Busse J, Dittrich M, Flieder T, Alban S, Knabbe C, Birschmann I. Dabigatran, rivaroxaban, apixaban, argatroban and fondaparinux and their effects on coagulation POC and platelet function tests. Clin Chem Lab Med. 2014;52(6):835–44.PubMedCrossRefGoogle Scholar
  191. 191.
    Grottke O, van Ryn J, Spronk HM, Rossaint R. 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. 2014;18(1):R27.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Honickel M, Treutler S, van Ryn J, Tillmann S, Rossaint R, Grottke O. Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab. Thromb Haemost. 2015;113(4):728–40.PubMedCrossRefGoogle Scholar
  193. 193.
    Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Görlinger K, Haas T, Imberger G, Jacob M, Lancé M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelsø AJ, Wouters P, Wyffels P. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol. 2013;30(6):270–382.PubMedCrossRefGoogle Scholar
  194. 194.
    Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363(19):1791–800.PubMedCrossRefGoogle Scholar
  195. 195.
    Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C. Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database Syst Rev. 2012;3, CD005011.PubMedGoogle Scholar
  196. 196.
    Haas T, Goobie S, Spielmann N, et al. Improvements in patient blood management for pediatric craniosynostosis surgery using a ROTEM() -assisted strategy - feasibility and costs. Paediatr Anaesth. 2014;24:774–80.PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Nienaber U, Innerhofer P, Westermann I, Schöchl H, Attal R, Breitkopf R, Maegele M. The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. Injury. 2011;42(7):697–701.PubMedCrossRefGoogle Scholar
  198. 198.
    Spalding GJ, Hartrumpf M, Sierig T, Oesberg N, Kirschke CG, Albes JM. Cost reduction of perioperative coagulation management in cardiac surgery: value of “bedside” thrombelastography (ROTEM). Eur J Cardiothorac Surg. 2007;31(6):1052–7.PubMedCrossRefGoogle Scholar
  199. 199.
    Görlinger K, Kozek-Langenecker SA. Economic aspects and organization. In: Marcucci CE, Schoettker P, editors. Perioperative hemostasis: coagulation for anesthesiologists. Berlin: Springer; 2015. p. 412–45.Google Scholar
  200. 200.
    Stokes ME, Ye X, Shah M, Mercaldi K, Reynolds MW, Rupnow MF, Hammond J. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Serv Res. 2011;11:135.PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Campbell HE, Stokes EA, Bargo DN, Curry N, Lecky FE, Edwards A, Woodford M, Seeney F, Eaglestone S, Brohi K, Gray AM, Stanworth SJ. Quantifying the healthcare costs of treating severely bleeding major trauma patients: a national study for England. Crit Care. 2015;19(1):276.PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Zbrozek A, Magee G. Cost of bleeding in trauma and complex cardiac surgery. Clin Ther. 2015;37(9):1966–74.PubMedCrossRefGoogle Scholar
  203. 203.
    Whiting P, Al M, Westwood M, Ramos IC, Ryder S, Armstrong N, Misso K, Ross J, Severens J, Kleijnen J. 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.CrossRefGoogle Scholar
  204. 204.
    Corral M, Ferko N, Hollmann S, Broder MS, Chang E. Health and economic outcomes associated with uncontrolled surgical bleeding: a retrospective analysis of the Premier Perspectives Database. Clinicoecon Outcomes Res. 2015;7:409–21.PubMedPubMedCentralGoogle Scholar
  205. 205.
    Craig J, Aguiar-Ibanez R, Bhattacharya S, Downie S, Duffy S, Kohli H, Nimmo A, Trueman P, Wilson S, Yunni Y. HTA Programme: Health Technology Assessment Report 11: The clinical and cost effectiveness of thromboelastography/thromboelastometry. Glasgow: NHS Quality Improvement Scotland; 2008. http://www.healthcareimprovementscotland.org/previous_resources/hta_report/hta/hta_11.aspx. ISBN 1-84404-995-0.
  206. 206.
    HealthPACT Seretariat. Health Policy Advisory Committee on Technology. Technology Brief: Rotational thromboelastometry (ROTEM)—targeted therapy for coagulation management in patients with massive bleeding. State of Queensland (Queensland Health), Australia, November 2012; http://www.health.qld.gov.au/healthpact/docs/briefs/WP024.pdf
  207. 207.
    NICE diagnostics guidance 13: Detecting, managing and monitoring haemostasis: viscoelastometric point-of-care testing (ROTEM, TEG and Sonoclot systems). National Institute for Health and Care Excellence (NICE); August 2014; ISBN: 978-1-4731-0688-8; www.nice.org.uk/dg13; http://www.nice.org.uk/guidance/dg13/resources/guidance-detecting-managing-and-monitoring-haemostasis-viscoelastometric-pointofcare-testing-rotem-teg-and-sonoclot-systems-pdf
  208. 208.
    Görlinger K, Schlenke P. Patient blood management: clinical hemotherapy and hemostasis management in perioperative settings. Transfus Med Hemother. 2012;39(2):57–8.PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Bolliger D, Tanaka KA. Roles of thrombelastography and thromboelastometry for patient blood management in cardiac surgery. Transfus Med Rev. 2013;27(4):213–20.PubMedCrossRefGoogle Scholar
  210. 210.
    Theusinger OM, Stein P, Spahn DR. Applying ‘Patient Blood Management’ in the trauma center. Curr Opin Anaesthesiol. 2014;27(2):225–32.PubMedCrossRefGoogle Scholar
  211. 211.
    Leahy MF, Roberts H, Mukhtar SA, Farmer S, Tovey J, Jewlachow V, Dixon T, Lau P, Ward M, Vodanovich M, Trentino K, Kruger PC, Gallagher T, Koay A, Hofmann A, Semmens JB. Towler S; Western Australian Patient Blood Management Program. A pragmatic approach to embedding patient blood management in a tertiary hospital. Transfusion. 2014;54(4):1133–45.PubMedCrossRefGoogle Scholar
  212. 212.
    Meybohm P, Fischer DP, Geisen C, Müller MM, Weber CF, Herrmann E, Steffen B, Seifried E, Zacharowski K, German PBM Study Core Group. Safety and effectiveness of a Patient Blood Management (PBM) program in surgical patients - the study design for a multi-centre prospective epidemiologic non-inferiority trial. BMC Health Serv Res. 2014;14:576.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Klaus Görlinger
    • 1
    • 2
    Email author
  • Jameel Iqbal
    • 3
  • Daniel Dirkmann
    • 1
  • Kenichi A. Tanaka
    • 4
  1. 1.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital EssenEssenGermany
  2. 2.Tem International GmbHMunichGermany
  3. 3.Department of Clinical PathologyWest Los Angeles Veterans Administration HospitalLos AngelesUSA
  4. 4.Department of Anesthesiology, Division of Cardiothoracic AnesthesiologyUniversity of Maryland Medical CenterBaltimoreUSA

Personalised recommendations