Journal of Cardiothoracic and Vascular Anesthesia
Volume 22, Issue 5 , Pages 675-680 , October 2008

Monitoring Recombinant Factor VIIa Treatment: Efficacy Depends on High Levels of Fibrinogen in a Model of Severe Dilutional Coagulopathy

Presented in part at the annual meeting of the American Society of Anesthesiologists, Chicago, IL, October 15-17, 2006.

  • Michael T. Ganter, MD

      Affiliations

    • Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland
    • ,
  • Saskia Schmuck, MD

      Affiliations

    • Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital, Zurich, Switzerland
    • ,
  • Christine R. Hamiel, BS

      Affiliations

    • Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, CO
    • ,
  • Paul E. Wischmeyer, MD

      Affiliations

    • Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, CO
    • ,
  • Daniela Heule, MD

      Affiliations

    • Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital, Zurich, Switzerland
    • ,
  • Andreas Zollinger, MD

      Affiliations

    • Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital, Zurich, Switzerland
    • ,
  • Christoph K. Hofer, MD

      Affiliations

    • Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital, Zurich, Switzerland
    • Corresponding Author InformationAddress reprint requests to Christoph K. Hofer, MD, Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital Zurich, Birmensdorferstr 497, 8063 Zurich, Switzerland

References 

  1. Levi M, Peters M, Buller HR. Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: A systematic review. Crit Care Med. 2005;33:883–890
  2. Boffard KD, Riou B, Warren B, et al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: Two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma. 2005;59:8–15
  3. Shander A, Goodnough LT, Ratko T, et al. Consensus recommendations for the off-label use of recombinant human factor VIIa (NovoSeven) therapy. Pharm Ther. 2005;30:644–658
  4. Vincent JL, Rossaint R, Riou B, et al. Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding—A European perspective. Crit Care. 2006;10:R120
  5. Ganguly S, Spengel K, Tilzer LL, et al. Recombinant factor VIIa: Unregulated continuous use in patients with bleeding and coagulopathy does not alter mortality and outcome. Clin Lab Haematol. 2006;28:309–312
  6. Sorensen B, Ingerslev J. Thromboelastography and recombinant factor VIIa-hemophilia and beyond. Semin Hematol. 2004;41:140–144
  7. Sorensen B, Ingerslev J. Whole blood clot formation phenotypes in hemophilia A and rare coagulation disorders (Patterns of response to recombinant factor VIIa). J Thromb Haemost. 2004;2:102–110
  8. Kawaguchi C, Takahashi Y, Hanesaka Y, et al. The in vitro analysis of the coagulation mechanism of activated factor VII using thromboelastogram. Thromb Haemost. 2002;88:768–772
  9. Pusateri AE, Park MS. Mechanistic implications for the use and monitoring of recombinant activated factor VII in trauma. Crit Care. 2005;9(suppl):S15–S24
  10. Engstrom M, Reinstrup P, Schott U. An in vitro evaluation of standard rotational thromboelastography in monitoring of effects of recombinant factor VIIa on coagulopathy induced by hydroxyethyl starch. BMC Blood Disord. 2005;5:3
  11. Sorensen B, Johansen P, Christiansen K, et al. Whole blood coagulation thromboelastographic profiles employing minimal tissue factor activation. J Thromb Haemost. 2003;1:551–558
  12. Rossaint R, Cerny V, Coats TJ, et al. Key issues in advanced bleeding care in trauma. Shock. 2006;26:322–331
  13. 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
  14. Singbartl K, Innerhofer P, Radvan J, et al. Hemostasis and hemodilution: A quantitative mathematical guide for clinical practice. Anesth Analg. 2003;96:929–935
  15. Fenger-Eriksen C, Anker-Moller E, Heslop J, et al. Thromboelastographic whole blood clot formation after ex vivo addition of plasma substitutes: Improvements of the induced coagulopathy with fibrinogen concentrate. Br J Anaesth. 2005;94:324–329
  16. Fries D, Innerhofer P, Reif C, et al. The effect of fibrinogen substitution on reversal of dilutional coagulopathy: An in vitro model. Anesth Analg. 2006;102:347–351
  17. De LC, Calatzis A, Welsch U, et al. Fibrinogen concentrate reverses dilutional coagulopathy induced in vitro by saline but not by hydroxyethyl starch 6%. Anesth Analg. 2006;102:1194–1200
  18. Fries D, Krismer A, Klingler A, et al. Effect of fibrinogen on reversal of dilutional coagulopathy: A porcine model. Br J Anaesth. 2005;95:172–177
  19. Egli GA, Zollinger A, Seifert B, et al. Effect of progressive haemodilution with hydroxyethyl starch, gelatin and albumin on blood coagulation. Br J Anaesth. 1997;78:684–689
  20. Niemi TT, Suojaranta-Ylinen RT, Kukkonen SI, et al. Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery. Anesth Analg. 2006;102:998–1006
  21. Luddington RJ. Thromboelastography/thromboelastometry. Clin Lab Haematol. 2005;27:81–90
  22. Hett DA, Walker D, Pilkington SN, et al. Sonoclot analysis. Br J Anaesth. 1995;75:771–776
  23. 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 thromboelastography. J Thromb Haemost. 2005;3:2039–2043
  24. Nielsen VG. A comparison of the thromboelastograph and the ROTEM. Blood Coagul Fibrinolysis. 2007;18:247–252
  25. Ganter MT, Hofer CK: Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg (in press)
  26. Sorensen B, Ingerslev J. Tailoring haemostatic treatment to patient requirements—An update on monitoring haemostatic response using thromboelastography. Haemophilia. 2005;11(suppl):1–6
  27. Fries D, Haas T, Klingler A, et al. Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy—A porcine model. Br J Anaesth. 2006;97:460–467
  28. O'Connell KA, Wood JJ, Wise RP, et al. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA. 2006;295:293–298
  29. Lichtman AD, Carullo V, Minhaj M, et al. Case 6—2007: Massive intraoperative thrombosis and death after recombinant activated factor VII administration. J Cardiothorac Vasc Anesth. 2007;21:897–902
  30. Warren O, Mandal K, Hadjianastassiou V, et al. Recombinant activated factor VII in cardiac surgery: A systematic review. Ann Thorac Surg. 2007;83:707–714
  31. Karkouti K, Beattie WS, Crowther MA, et al. The role of recombinant factor VIIa in on-pump cardiac surgery: Proceedings of the Canadian Consensus Conference. Can J Anaesth. 2007;54:573–582
  32. Martinowitz U, Michaelson M. Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: A report by the Israeli Multidisciplinary rFVIIa Task Force. J Thromb Haemost. 2005;3:640–648
  33. Sorensen B, Fenger-Eriksen C, Ingerslev J. Recombinant factor VIIa fails to correct coagulopathy induced by haemodilution with colloid. Br J Anaesth. 2005;94:862–863
  34. Schreiber MA, Holcomb JB, Hedner U, et al. The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries. J Trauma. 2002;53:252–257
  35. Sondeen JL, Pusateri AE, Hedner U, et al. Recombinant factor VIIa increases the pressure at which rebleeding occurs in porcine uncontrolled aortic hemorrhage model. Shock. 2004;22:163–168

 M.T. Ganter and S. Schmuck contributed equally to this work.

 Supported by Pentapharm GmbH (Munich, Germany), Sienco Inc (Arvada, CO), and Novo Nordisk (Cophenhagen, Denmark). An educational grant for this study was provided by ZLB Behring (Berne, Switzerland). None of the authors is related to or has financial interests in the manufacturers of products studied.

PII: S1053-0770(08)00023-2

doi: 10.1053/j.jvca.2008.01.017

Journal of Cardiothoracic and Vascular Anesthesia
Volume 22, Issue 5 , Pages 675-680 , October 2008

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