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Recombinant Activated Factor VII: The Delicate Balance between Efficacy and Safety

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Intensive Care Medicine

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Abstract

Endogenous activated factor VII (FVIIa) plays a crucial role in the effective coagulation process. The clotting drug NovoSeven® (Novo Nordisk A/S, Bagsvaerd, Denmark) is structurally nearly identical to endogenous FVIIa and is produced by recombination from a baby hamster kidney cell line. Supra-physiologic concentrations of FVIIa are achieved by the administration of pharmacological doses of recombinant FVIIa (rFVIIa). To generate thrombin, rFVIIa needs either tissue factor or activated platelets (tissue factor-independent generation). Consequently, rFVIIa is approved for the prevention and the treatment of bleeding in patients with a range of congenital hemostatic disorders, mainly hemophilia. Its high efficacy in various hemostatic defects has oriented its application to the perioperative setting, trauma, and ICU patients. Over the last five years, the estimated number of patients treated with rVIIa has grown rapidly, mainly for off-license indications.

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References

  1. Diprose P, Herbertson MJ, O’Shaughnessy D, Gill RS (2005) Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study. Br J Anaesth 95: 596–602

    Article  PubMed  CAS  Google Scholar 

  2. Friederich PW, Henny CP, Messelink EJ, et al (2003) Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a doubleblind placebo-controlled randomised trial. Lancet 361: 201–205

    Article  PubMed  CAS  Google Scholar 

  3. Ekert H, Brizard C, Eyers R, Cochrane A, Henning R (2006) Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy. Blood Coagul Fibrinolysis 17: 389–395

    Article  PubMed  CAS  Google Scholar 

  4. Lodge JP, Jonas S, Oussoultzoglou E, et al (2005) Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial. Anesthesiology 102: 269–275

    Article  PubMed  CAS  Google Scholar 

  5. Lodge JP, Jonas S, Jones RM, et al (2005) Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl 11: 973–979

    Article  PubMed  Google Scholar 

  6. Planinsic RM, van der Meer J, Testa G, et al (2005) Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transpl 11: 895–900

    Article  PubMed  Google Scholar 

  7. Raobaikady R, Redman J, Ball JA, Maloney G, Grounds RM (2005) Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial. Br J Anaesth 94: 586–591

    Article  PubMed  CAS  Google Scholar 

  8. Shao YF, Yang JM, Chau GY, et al (2006) Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Am J Surg 191: 245–249

    Article  PubMed  CAS  Google Scholar 

  9. Boffard KD, Riou B, Warren B, et al (2005) 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 59: 8–15

    Article  PubMed  CAS  Google Scholar 

  10. Bosch J, Thabut D, Bendtsen F, et al (2004) Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 127: 1123–1130

    Article  PubMed  CAS  Google Scholar 

  11. Chuansumrit A, Wangruangsatid S, Lektrakul Y, et al (2005) Control of bleeding in children with Dengue hemorrhagic fever using recombinant activated factor VII: a randomized, double-blind, placebo-controlled study. Blood Coagul Fibrinolysis 16: 549–555

    Article  PubMed  CAS  Google Scholar 

  12. Mayer SA, Brun NC, Begtrup K, et al (2005) Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 352: 777–785

    Article  PubMed  CAS  Google Scholar 

  13. Mayer SA, Brun NC, Broderick J, et al (2005) Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Stroke 36: 74–79

    Article  PubMed  CAS  Google Scholar 

  14. Pihusch M, Bacigalupo A, Szer J, et al (2005) Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation. J Thromb Haemost 3: 1935–1944

    Article  PubMed  CAS  Google Scholar 

  15. Stanworth SJ, Birchall J, Doree CJ, Hyde C (2007) Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database Syst Rev: CD005011

    Google Scholar 

  16. Conen A, Weisser M, Tsakiris DA, Siegemund M (2007) Failure of recombinant factor VIIa in a patient with severe polymicrobial sepsis and postoperative uncontrolled intraabdominal bleeding. BMC Infect Dis 7: 34

    Article  PubMed  CAS  Google Scholar 

  17. Thomas GO, Dutton RP, Hemlock B, et al (2007) Thromboembolic complications associated with factor VIIa administration. J Trauma 62: 564–569

    Article  PubMed  Google Scholar 

  18. Sugg RM, Gonzales NR, Matherne DE, et al (2006) Myocardial injury in patients with intracerebral hemorrhage treated with recombinant factor VIIa. Neurology 67: 1053–1055

    Article  PubMed  CAS  Google Scholar 

  19. Broderick J, Connolly S, Feldmann E, et al (2007) Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 38: 2001–2023

    Article  PubMed  Google Scholar 

  20. Mayer SA, (2007) Complications in patients with intracerebral hemorrhage treated with recombinant factor VIIa. Neurology 69: 319–320

    Article  PubMed  Google Scholar 

  21. Karkouti K, Beattie WS, Wijeysundera DN, et al (2005) Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity score-matched case-control analysis. Transfusion 45: 26–34

    Article  PubMed  CAS  Google Scholar 

  22. Huber-Wagner S, Qvick M, Mussack T, et al (2007) Massive blood transfusion and outcome in 1062 polytrauma patients: a prospective study based on the Trauma Registry of the German Trauma Society. Vox Sang 92: 69–78

    Article  PubMed  CAS  Google Scholar 

  23. Perkins JG, Schreiber MA, Wade CE, Holcomb JB (2007) Early versus late recombinant factor VIIa in combat trauma patients requiring massive transfusion. J Trauma 62: 1095–1099

    Article  PubMed  CAS  Google Scholar 

  24. Hedner U, Ezban M (2007) Tissue Factor and Factor VIIa as Therapeutic Targets in Disorders of Hemostasis. Annu Rev Med [Epub ahead of print]

    Google Scholar 

  25. Gerotziafas GT, Chakroun T, Depasse F, Arzoglou P, Samama MM, Elalamy I (2004) The role of platelets and recombinant factor VIIa on thrombin generation, platelet activation and clot formation. Thromb Haemost 91: 977–985

    PubMed  CAS  Google Scholar 

  26. Lisman T, Adelmeijer J, Cauwenberghs S, Van Pampus EC, Heemskerk JW, De Groot PG (2005) Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count. J Thromb Haemost 3: 742–751

    Article  PubMed  CAS  Google Scholar 

  27. Bijsterveld NR, Moons AH, Boekholdt SM, et al (2002) Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation 106: 2550–2554

    Article  PubMed  CAS  Google Scholar 

  28. Fridberg MJ, Hedner U, Roberts HR, Erhardtsen E (2005) A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects. Blood Coagul Fibrinolysis 16: 259–266

    Article  PubMed  CAS  Google Scholar 

  29. Wegert W, Harder S, Bassus S, Kirchmaier CM (2005) Platelet-dependent thrombin generation assay for monitoring the efficacy of recombinant Factor VIIa. Platelets 16: 45–50

    Article  PubMed  CAS  Google Scholar 

  30. Arkin S, Blei F, Fetten J, et al (2000) Human coagulation factor FVIIa (recombinant) in the management of limb-threatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use programme in patients with severe haemophilia or with acquired inhibitors. Blood Coagul Fibrinolysis 11: 255–259

    PubMed  CAS  Google Scholar 

  31. Negrier C, Hay CR (2000) The treatment of bleeding in hemophilic patients with inhibitors with recombinant factor VIIa. Semin Thromb Hemost 26: 407–412

    Article  PubMed  CAS  Google Scholar 

  32. Roberts HR, Monroe DM, 3rd, Hoffman M (2004) Safety profile of recombinant factor VIIa. Semin Hematol 41: 101–108

    Article  PubMed  CAS  Google Scholar 

  33. Aledort LM (2004) Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost 2: 1700–1708

    Article  PubMed  CAS  Google Scholar 

  34. Levy JH, Fingerhut A, Brott T, Langbakke IH, Erhardtsen E, Porte RJ (2006) Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile. Transfusion 46: 919–933

    Article  PubMed  CAS  Google Scholar 

  35. O’Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM (2006) Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA 295: 293–298

    Article  CAS  Google Scholar 

  36. Karkouti K, Yau TM, Riazi S, et al (2006) Determinants of complications with recombinant factor VIIa for refractory blood loss in cardiac surgery. Can J Anaesth 53: 802–809

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Anesthesiology, Institut de Cardiologie, 5000 Rue Belanger Est, Montreal, QB HIT 1C8, Canada

    S. Bélisle & J. -F. Hardy

  2. Department of Anesthesiology, CHU Brugmann, 4 Place Arthur Van Gehuchten, 1020, Brussels, Belgium

    P. Van der Linden

Authors
  1. S. Bélisle
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  2. J. -F. Hardy
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  3. P. Van der Linden
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Editor information

Editors and Affiliations

  1. Department of Intensive Care Erasme Hospital, Université libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium

    Jean-Louis Vincent MD, PhD, FCCM, FCCP (Head) (Head)

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Bélisle, S., Hardy, J.F., Van der Linden, P. (2008). Recombinant Activated Factor VII: The Delicate Balance between Efficacy and Safety. In: Vincent, JL. (eds) Intensive Care Medicine. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77383-4_70

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  • DOI: https://doi.org/10.1007/978-0-387-77383-4_70

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-77382-7

  • Online ISBN: 978-0-387-77383-4

  • eBook Packages: MedicineMedicine (R0)

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