Advertisement

The use of recombinant activated coagulation factor VII for spine surgery

  • Richard B. Weiskopf
Conference paper

Abstract

This article focuses on our current understanding of the role of activated coagulation factor VII (FVIIa) in coagulation, the current evidence regarding the efficacy and safety of recombinant FVIIa (rFVIIa), and thoughts regarding the use of rFVIIa in spine surgery. rFVIIa is approved in many countries (including the European Union and the USA) for patients with hemophilia and inhibitors (antibodies) to coagulation factors VIII or IX. High circulating concentrations of FVIIa, achieved by exogenous administration, initiate hemostasis by combining with tissue factor at the site of injury, producing thrombin, activating platelets and coagulation factors II, IX and X, thus providing for the full thrombin burst that is essential for hemostasis. This “bypass” therapy has led some clinicians to use rFVIIa “off-label” for disorders of hemostasis other than hemophilia. Based on clinical experience, case reports and limited information from clinical trials, rFVIIa may be efficacious in states of decreased concentration of coagulation factors, thrombocytopenia, and at least some states of altered platelet function. The former two can occur intra-operatively during spinal surgery as a consequence of substantial blood loss and normal consumption. Preliminary reports have indicated that rFVIIa does not increase the perioperative incidence of thromboembolic events. However, full reports from large clinical trials regarding the efficacy and safety of rFVIIa in settings other than hemophilia have yet to appear in peer-reviewed publications. Until adequate data demonstrating safety and efficacy are fully reported, it would seem appropriate to reserve the use of rFVIIa in spinal surgery to those instances where conventional therapy cannot provide adequate hemostasis, and “rescue” therapy is required.

Keywords

Blood loss Coagulation Coagulopathy Hemostasis Recombinant coagulation factor VIIa 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Béguin S, Keularts I (1999) On the coagulation of platelet-rich plasma. Haemostasis 29:50–57CrossRefPubMedGoogle Scholar
  2. 2.
    Bernstein DE, Jeffers L, Erhardtsen E et al (1997) Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study. Gastroenterology 113:1930–1937CrossRefPubMedGoogle Scholar
  3. 3.
    Berntorp E, Stigendal L, Lethagen S, Olofsson L, Hedner U (2000) NovoSeven in warfarin-treated patients. Blood Coagul Fibrinolysis [Suppl 1] S113–S115Google Scholar
  4. 4.
    Billon S, Le Niger C, Escoffre-Barbe M, Vicariot M, Abgrall JF (2001) The use of recombinant factor VIIa (NovoSeven) in a patient with a factor XI deficiency and a circulating anticoagulant. Blood Coagul Fibrinolysis 12: 551–553CrossRefPubMedGoogle Scholar
  5. 5.
    Blomback B, Carlsson K, Fatah K, Hessel B, Procyk R (1994) Fibrin in human plasma: gel architectures governed by rate and nature of fibrinogen activation. Thromb Res 75:521–538CrossRefPubMedGoogle Scholar
  6. 6.
    Bouwmeester FW, Jonkhoff AR, Verheijen RH, van Geijn HP (2003) Successful treatment of life-threatening postpartum hemorrhage with recombinant activated factor VII. Obstet Gynecol 101:1174–1176PubMedGoogle Scholar
  7. 7.
    Ciavarella N, Schiavoni M, Valenzano E, Mangini F, Inchingolo F (1996) Use of recombinant factor VIIa (NovoSeven) in the treatment of two patients with type III von Willebrand’s disease and an inhibitor against von Willebrand factor. Haemostasis 26[Suppl 1]:150–154Google Scholar
  8. 8.
    Collet J, Park D, Lesty C, Soria J, Montalescot G, Weisel J (2000) Influence of fibrin network conformation and fibrin diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy. Arterioscler Thromb Vasc Biol 20: 1354–1361PubMedGoogle Scholar
  9. 9.
    Collet J, Lesty C, Montalescot G, Weisel J (2003) Dynamic changes of fibrin architecture during fibrin formation and intrinsic fibrinolysis of fibrinrich clots. J Biol Chem 278:21331–21335CrossRefPubMedGoogle Scholar
  10. 10.
    Deveras R, Kessler C (2002) Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa. Ann Intern Med 137:884–888PubMedGoogle Scholar
  11. 11.
    Erhardtsen E (2000) Pharmacokinetics of recombinant activated factor VII (rFVIIa). Semin Thromb Hemost 26: 385–391CrossRefPubMedGoogle Scholar
  12. 12.
    Erhardtsen E, Nony P, Dechavanne M, Ffrench P, Boissel J, Hedner U (1998) The effect of recombinant factor VIIa (NovoSeven) in healthy volunteers receiving acenocoumarol to an international normalized ratio above 2.0. Blood Coagul Fibrinolysis 9:741–748PubMedGoogle Scholar
  13. 13.
    Friederich P, Henny C, Messelink E, Geerdink M, Keller T, Kurth KH, Büller H, Levi M (2003) Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet 361:201–205CrossRefPubMedGoogle Scholar
  14. 14.
    He S, Blomback M, Jacobsson Ekman G, Hedner U (2003) The role of recombinant factor VIIa (FVIIa) in fibrin structure in the absence of FVIII/FIX. J Thromb Haemost 1:1215–1219CrossRefPubMedGoogle Scholar
  15. 15.
    Hedner U (2000) Recombinant coagulation factor VIIa: from the concept to clinical application in hemophilia treatment in 2000. Semin Thromb Hemost 26:363–366CrossRefPubMedGoogle Scholar
  16. 16.
    Hedner U, Kisiel W (1983) Use of human factor VIIa in the treatment of two hemophilia A patients with high-titer inhibitors. J Clin Invest 71:1836–1841PubMedGoogle Scholar
  17. 17.
    Hedner U, Glazer S, Pingel K, Alberts K, Blomback M, Schulman S, Johnson H (1988) Successful use of recombinant factor VIIa in a patient with severe hemophilia A during synovectomy. Lancet 2:1193CrossRefPubMedGoogle Scholar
  18. 18.
    Hedner U, Bjorn S, Bernvil S, Tengborn L, Stigendal L (1989) Clinical experience with human plasma-derived factor VIIa in patients with hemophilia A and high titer inhibitors. Haemostasis 19: 335–343PubMedGoogle Scholar
  19. 19.
    Hendriks H, Meijer K, De Wolf J, Klompmaker I, Porte R, De Kam P, Hagenaars A, Melsen T, Slooff M, van der Meer J (2001) Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation. Transplantation 71:402–405CrossRefPubMedGoogle Scholar
  20. 20.
    Hoffman R, Eliakim R, Zuckerman T, Rowe JM, Brenner B (2003) Successful use of recombinant activated factor VII in controlling upper gastrointestinal bleeding in a patient with relapsed acute myeloid leukemia. J Thromb Haemost 1:606–608CrossRefPubMedGoogle Scholar
  21. 21.
    Jeffers L, Chalasani N, Balart L, Pyrsopoulos N, Erhardtsen E (2002) Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy. Gastroenterology 123:118–126CrossRefPubMedGoogle Scholar
  22. 22.
    Kenet G, Walden R, Eldad A, Martinowitz U (1999) Treatment of traumatic bleeding with recombinant factor VIIa [letter]. Lancet 354:1879PubMedGoogle Scholar
  23. 23.
    Kjalke M, Ezban M, Monroe DM, Hoffman M, Roberts HR, Hedner U (2001) High-dose factor VIIa increases initial thrombin generation and mediates faster platelet activation in the thrombocytopenia-like conditions in a cell-based model system. Br J Haematol 114:114–120CrossRefPubMedGoogle Scholar
  24. 24.
    Kristensen J, Killander A, Hippe E, Hellegerg C, Ellegard J, Holm M, Kutt, J, Mellqvist U, Johansson J, Glazer S, Hedner U (1996) Clinical experience with recombinant factor VIIa in patients with thrombocytopenia. Haemostasis 26[Suppl 1]:159–164PubMedGoogle Scholar
  25. 25.
    Leibovitch L, Kenet G, Mazor K, Matok I, Vardi A, Barzilay Z, Paret G (2003) Recombinant activated factor VII for life-threatening pulmonary hemorrhage after pediatric cardiac surgery. Pediatr Crit Care Med 4:444–446CrossRefPubMedGoogle Scholar
  26. 26.
    Martinowitz U, Kenet G, Segal E, Luboshitz J, Lubetsky A, Ingerslev J, Lynn M (2001) Recombinant activated factor VII for adjunctive hemorrhage control in trauma. J Trauma 51(3):431–438PubMedGoogle Scholar
  27. 27.
    McDonagh J, Fukue H (1996) Determinants of substrate specificity for factor XIII. Semin Thromb Hemost 22:369–376PubMedGoogle Scholar
  28. 28.
    Monroe DM, Hoffman M, Oliver JA, Roberts HR (1997) Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol 99(3):542–547CrossRefPubMedGoogle Scholar
  29. 29.
    Morenski JD, Tobias JD, Jimenez DF (2003) Recombinant activated factor VII for cerebral injury-induced coagulopathy in pediatric patients. Report of three cases and review of the literature. J Neurosurg 98: 611–666PubMedGoogle Scholar
  30. 30.
    Nesheim M, Wang W, Boffa M, Nagashima M, Morser J, Bajzar L (1997) Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost 78:386–391PubMedGoogle Scholar
  31. 31.
    O’Connell NM (2004) Factor XI deficiency. Semin Hematol 41:76–81CrossRefPubMedGoogle Scholar
  32. 32.
    Pastores SM, Papadopoulos E, Voigt L, Halpern NA (2003) Diffuse alveolar hemorrhage after allogeneic hematopoietic stem-cell transplantation: treatment with recombinant factor VIIa. Chest 124:2400–2403CrossRefPubMedGoogle Scholar
  33. 33.
    Peters M, Heijboer H (1998) Treatment of a patient with Bernard-Soulier syndrome and recurrent nosebleeds with recombinant factor VIIa. Thromb Haemost 80:352PubMedGoogle Scholar
  34. 34.
    Roberts HR, Monroe DM, Escobar M (2004) Current concepts of hemostasis: implications for therapy. Anesthesiology 100:722–730CrossRefPubMedGoogle Scholar
  35. 35.
    Stratmann G, Russell IA, Merrick SH (2003) Use of recombinant factor VIIa as a rescue treatment for intractable bleeding following repeat aortic arch repair. Ann Thorac Surg 76:2094–2097CrossRefPubMedGoogle Scholar
  36. 36.
    Svartholm E, Ammerhagen V, Länne T (2002) Treatment of bleeding in severe necrotizing pancreatitis with recombinant factor VIIa (letter). Anesthesiology 96:1528CrossRefGoogle Scholar
  37. 37.
    Tengborn L, Petruson B (1996) A patient with Glanzmann thrombasthenia and epistaxis successfully treated with recombinant factor VIIa. Thromb Haemost 75:981–982Google Scholar
  38. 38.
    Tobias JD (2002) Synthetic factor VIIa to treat dilutional coagulopathy during posterior spinal fusion in two children. Anesthesiology 96:1522–1555CrossRefPubMedGoogle Scholar
  39. 39.
    Vidarsson B, Onundarson PT (2000) Recombinant factor VIIa for bleeding in refractory thrombocytopenia (letter). Thromb Haemost 83:634–635PubMedGoogle Scholar
  40. 40.
    Weisel J, Veklich Y, Collet J, Francis C (1999) Structural studies of fibrinolysis by electron and light microscopy. Thromb Haemost. 82:277–282PubMedGoogle Scholar
  41. 41.
    Wildgoose P, Nemerson Y, Hansen LL, Nielsen FE, Glazer S, Hedner U (1992) Measurement of basal levels of factor VIIa in hemophilia A and B patients. Blood 80:25–28PubMedGoogle Scholar
  42. 42.
    Zaaroor M, Bar-Lavie M (2004) The use of recombinant factor VIIa in head injury: a report of five cases. Semin Hematol 41[Suppl 1]:175–176CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Richard B. Weiskopf
    • 1
  1. 1.Department of Anesthesia and Cardiovascular Research InstituteUniversity of California, San FranciscoSan FranciscoUSA

Personalised recommendations