Neurocritical Care

, Volume 10, Issue 1, pp 55–60 | Cite as

Perioperative Use of Recombinant Factor VII to Prevent Intraoperative Aneurysm Rupture in High Risk Patients: A Preliminary Safety Evaluation

  • Eric S. Nussbaum
  • Tariq M. Janjua
  • Archie Defillo
  • Penny Sinner
  • Andrea Zelensky



The authors present a safety evaluation of the perioperative use of recombinant activated factor VII (rFVIIa) in a series of subarachnoid hemorrhage patients undergoing microsurgical aneurysm clipping.


We performed a retrospective chart review of the records of 18 consecutive subarachnoid hemorrhage patients who underwent craniotomy for aneurysm clipping and received an intraoperative dose of rFVIIa. In each case, the aneurysm was felt to be a “high risk” lesion for intraoperative rupture either because it had bled multiple times prior to surgery or based on anatomical considerations. All complications were recorded whether or not they were attributed to the use of rFVIIa.


Eighteen patients, 7 men and 11 women, ranging in age from 42 to 85 years were included in this review. Nine patients (50%) were either Hunt/Hess Grades IV or V. Six patients developed clinically significant cerebral vasospasm. Fifteen patients required ventricular drainage on admission, and seven patients ultimately required a ventriculoperitoneal shunt. One lower extremity deep venous thrombosis and seven upper extremity venous thromboses in association with peripherally inserted central catheter (PICC) lines were identified on screening Doppler evaluations. There were no associated pulmonary emboli. No aneurysm ruptured intraoperatively.


We describe our experience with the use of a single dose of rFVIIa administered perioperatively in an attempt to decrease the rate of intraoperative aneurysm rupture in patients undergoing microsurgical aneurysm clipping. There were no significant immediate or long-term adverse effects attributable to the use of rFVIIa in this group, and we encountered no intraoperative ruptures in this relatively small series.


Aneurysm Brain Factor VII Rupture Subarachnoid hemorrhage 


  1. 1.
    Adams HP Jr, Kassell NF, Torner JC, Nibbelink DW, Sahs AL. Early management of aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg. 1981;54:141–5.PubMedGoogle Scholar
  2. 2.
    Arkin S, Cooper HA, Hutter JJ, Miller S, Schmidt ML, Seibel NL, et al. Activated recombinant human coagulation factorVII therapy for intracranial hemorrhage in patients with hemophilia A or B with inhibitors. Results of the NovoSeven emergency-use program. Haemostasis. 1998;28:93–8. doi: 10.1159/000022418.PubMedCrossRefGoogle Scholar
  3. 3.
    Batjer HH, Samson DS. Intraoperative aneurysmal rupture: incidence, outcome, and suggestions for surgical management. Neurosurgery. 1986;18:701–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 1997;28:1–5.PubMedGoogle Scholar
  5. 5.
    Chwajol M, Starke RM, Kim GH, Mayer SA, Connolly ES. Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage. Neurocrit Care. 2008;8:418–26. doi: 10.1007/s12028-008-9088-5.PubMedCrossRefGoogle Scholar
  6. 6.
    Dutton RP, McCunn M, Hyder M, D’Angelo M, O’Connor J, Hess JR, et al. Factor VIIa for correction of traumatic coagulopathy. J Trauma Inj Infect Crit Care. 2004;57:709–19. doi: 10.1097/01.TA.0000140646.66852.AB.CrossRefGoogle Scholar
  7. 7.
    Elijovich L, Higashida RT, Lawton MT, Duckwiler G, Giannotta S, Johnston C. Predictors and outcomes of intraprocedural rupture in patients treated for ruptured intracranial aneurysms. The CARAT study. Stroke. 2008;39:1501–6. doi: 10.1161/STROKEAHA.107.504670.PubMedCrossRefGoogle Scholar
  8. 8.
    Fewel ME, Park P. The emerging role of recombinant-activated factor VII in neurocritical care. Neurocrit Care. 2004;1:19–30. doi: 10.1385/NCC:1:1:19.PubMedCrossRefGoogle Scholar
  9. 9.
    Giannotta SL, Oppenheimer JH, Levy ML, Zelman V. Management of intraoperative rupture of aneurysm without hypotension. Neurosurgery. 1991;28:531–6. doi: 10.1097/00006123-199104000-00008.PubMedCrossRefGoogle Scholar
  10. 10.
    Gibbs JR, Corkill AGL. Use of antifibrinolytic agent (tranexamic acid) in the management of ruptured intracranial aneurysm. Postgrad Med J. 1971;47:199–200.PubMedCrossRefGoogle Scholar
  11. 11.
    Hawryluk GWJ, Cusimano MD. The role of recombinant factor VII in neurosurgery: hope or hype. J Neurosurg. 2006;105:859–68. doi: 10.3171/jns.2006.105.6.859.PubMedCrossRefGoogle Scholar
  12. 12.
    Hedner U. Dosing with recombinant Factor VIIa based on current evidence. Semin Hematol. 2004;41:35–9. doi: 10.1053/j.seminhematol.2003.11.008.PubMedCrossRefGoogle Scholar
  13. 13.
    Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg. 2002;97:771–8.PubMedGoogle Scholar
  14. 14.
    Hoffman M, Monroe DM III. A cell-based model of hemostasis. Thromb Haemost. 2001;85:958–65.PubMedGoogle Scholar
  15. 15.
    Ingerslev J. Efficacy and safety of recombinant factor VIIa in the prophylaxis of bleeding in various surgical procedures in hemophilic patients with factor VII and factor IX inhibitors. Semin Thromb Hemost. 2000;26:425–32. doi: 10.1055/s-2000-8463.PubMedCrossRefGoogle Scholar
  16. 16.
    Komotar RJ, Hahn DK, Kim GH, Khandji J, Mocco J, Mayer SA, et al. The impact of microsurgical fenestration of the lamina terminalis on shunt-dependent hydrocephalus and vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2008;62:123–32.PubMedGoogle Scholar
  17. 17.
    Lawton MT, Du R. Effect of the neurosurgeon’s surgical experience on outcomes from intraoperative aneurysm rupture. Neurosurgery. 2005;57:9–15. doi: 10.1227/01.NEU.0000163082.20941.EF.PubMedCrossRefGoogle Scholar
  18. 18.
    Leipzig TJ, Redelman K, Horner TG. Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy. J Neurosurg. 1997;86:220–5.PubMedGoogle Scholar
  19. 19.
    Leipzig TJ, Morgan J, Horner TG, Payner T, Redelman K, Johnson CS. Analysis of intraoperative rupture in the surgical treatment of 1694 saccular aneurysms. Neurosurgery. 2005;56:455–68. doi: 10.1227/01.NEU.0000154697.75300.C2.PubMedCrossRefGoogle Scholar
  20. 20.
    Lin J, Hanigan WC, Tarantino M, Wang J. The use of recombinant activated factor VII to reverse warfarin-induced anticoagulation in patients with hemorrhages in the central nervous system: preliminary findings. J Neurosurg. 2003;98:737–40.PubMedGoogle Scholar
  21. 21.
    Macdonald RL. Lumbar drainage after subarachnoid hemorrhage: does it reduce vasospasm and delayed hydrocephalus? Neurocrit Care. 2007;7:1–2. doi: 10.1007/s12028-007-0046-4.PubMedCrossRefGoogle Scholar
  22. 22.
    Martinowitz U, Kenet G, Segal E, Luboshitz J, Lubetsky A, Ingerslev J, et al. Recombinant activated factor VII for adjunctive hemorrhage control in trauma. J Trauma. 2001;51:431–9. doi: 10.1097/00005373-200109000-00002.PubMedCrossRefGoogle Scholar
  23. 23.
    Mayer SA. Ultra-early hemostatic therapy for intracerebral hemorrhage. Stroke. 2003;34:224–9. doi: 10.1161/01.STR.0000046458.67968.E4.PubMedCrossRefGoogle Scholar
  24. 24.
    Mayer SA, Brun NC, Broderick J, Davis S, Diringer MN, Skolnick BE, et al. Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Stroke. 2005;36:74–9. doi: 10.1161/01.STR.0000149628.80251.b8.PubMedCrossRefGoogle Scholar
  25. 25.
    Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005;352:777–85. doi: 10.1056/NEJMoa042991.PubMedCrossRefGoogle Scholar
  26. 26.
    Morenski JD, Tobias JD, Jimenez DF. Recombinant activated factor VII for cerebral injury-induced coagulopathy in pediatric patients. Report of three cases and review of the literature. J Neurosurg. 2003;98:611–6.PubMedGoogle Scholar
  27. 27.
    Mullan S, Dawley J. Antifibrinolytic therapy for intracranial aneurysm. J Neurosurg. 1968;28:21–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Nibbelink DW, Torner JC, Henderson WG. Intracranial aneurysms and subarachnoid hemorrhage. A cooperative study. Antifibrinolytic therapy in recent onset subarachnoid hemorrhage. Stroke. 1975;6:622–9.PubMedGoogle Scholar
  29. 29.
    Norlen G, Thulin CA. The use of antifibrinolytic substances in ruptured intracranial aneurysms. Neurochirurgia (Stuttg). 1969;12:100–2.Google Scholar
  30. 30.
    Nussbaum ES, Sebring LA, Ostanny I, Nelson WB. Transient cardiac standstill induced by adenosine in the management of intraoperative aneurysmal rupture: technical case report. Neurosurgery. 2000;47:240–3. doi: 10.1097/00006123-200007000-00053.PubMedCrossRefGoogle Scholar
  31. 31.
    O’Neill PA, Bluth M, Gloster ES, Wali D, Priovolos S, DiMaio TM, et al. Successful use of recombinant activated factor VII for trauma-associated hemorrhage in a patient without preexisting coagulopathy. J Trauma. 2002;52:400–5. doi: 10.1097/00005373-200202000-00034.PubMedCrossRefGoogle Scholar
  32. 32.
    Parameswaran R, Shapiro AD, Gill JC, Kessler CM. Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia Research Society Registry. Haemophilia. 2005;11:100–16. doi: 10.1111/j.1365-2516.2005.01075.x.PubMedCrossRefGoogle Scholar
  33. 33.
    Park P, Fewel ME, Garton HJ, Thompson BG, Hoff JT. Recombinant activated factor VII for the rapid correction of coagulopathy in nonhemophilic neurosurgical patients. Neurosurgery. 2003;53:34–9. doi: 10.1227/01.NEU.0000068830.54968.A8.PubMedCrossRefGoogle Scholar
  34. 34.
    Pickard JD, Kirkpatrick PJ, Melsen T, Andreasen RB, Gelling L, Fryer T, et al. Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage. Blood Coagul Fibrinolysis. 2000;11:S117–20.PubMedGoogle Scholar
  35. 35.
    Rizoli SB, Nascimiento B Jr, Osman F, Netto FS, Kiss A, Callum J, et al. Recombinant activated coagulation factor VII and bleeding trauma patients. J Trauma. 2006;61:1419–25. doi: 10.1097/01.ta.0000243045.56579.74.PubMedCrossRefGoogle Scholar
  36. 36.
    Roos Y. Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. STAR Study Group. Neurology. 2000;54:77–82.PubMedGoogle Scholar
  37. 37.
    Roos Y, Rinkel G, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid hemorrhage: a major update of a cochrane review. Stroke. 2003;34:2308–9. doi: 10.1161/01.STR.0000089030.04120.0E.PubMedCrossRefGoogle Scholar
  38. 38.
    Schramm J, Cedzich C. Outcome and management of intraoperative aneurysm rupture. Surg Neurol. 1993;40:26–30. doi: 10.1016/0090-3019(93)90165-W.PubMedCrossRefGoogle Scholar
  39. 39.
    Sorensen B, Johansen P, Nielsen GL, Sorensen JC, Ingerslev J. Reversal of the international normalized ratio with recombinant activated factor VII in central nervous system bleeding during warfarin thromboprophylaxis: clinical and biochemical aspects. Blood Coagul Fibrinolysis. 2003;14:469–77. doi: 10.1097/00001721-200307000-00007.PubMedCrossRefGoogle Scholar
  40. 40.
    Subramaniam S, Demchuk AM, Watson T, Barber PA, Hill MD. Unexpected posthemorrhagic hydrocephalus in patients treated with rFVIIa. Neurology. 2006;67:1096–9. doi: 10.1212/01.wnl.0000237321.60852.e7.PubMedCrossRefGoogle Scholar
  41. 41.
    Tovi D. The use of antifibrinolytic drugs to prevent early recurrent aneurismal subarachnoid hemorrhage. Acta Neurol Scand. 1973;49:163–75.PubMedGoogle Scholar
  42. 42.
    Tsementzis SA, Hitchcock ER, Meyer CH. Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms. A double-blind placebo-controlled study. Acta Neurochir (Wien). 1990;102:1–10. doi: 10.1007/BF01402177.CrossRefGoogle Scholar
  43. 43.
    Varelas P, Helms A, Sinson G, Spanaki M, Hacein-Bey L. Clipping or coiling of ruptured cerebral aneurysms and shunt-dependent hydrocephalus. Neurocrit Care. 2006;4:223–8. doi: 10.1385/NCC:4:3:223.PubMedCrossRefGoogle Scholar
  44. 44.
    Vermeulen M, Lindsay KW, Murray GD, Cheah F, Hijdra A, Muizelaar JP, et al. Antifibrinolytic treatment in subarachnoid hemorrhage. N Engl J Med. 1984;311:432–7.PubMedGoogle Scholar
  45. 45.
    Veshchev I, Elran H, Salame K. Recombinant coagulation factor VIIa for rapid preoperative correction of warfarin-related coagulopathy in patients with acute subdural hematoma. Med Sci Monit. 2002;8:CS98–100.PubMedGoogle Scholar
  46. 46.
    Wijdicks EF, Hasan D, Lindsay KW, Brouwers PJ, Hatfield R, Murray GD, et al. Short-term tranexamic acid treatment in aneurysmal subarachnoid hemorrhage. Stroke. 1989;20:1674–9.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Eric S. Nussbaum
    • 1
    • 2
  • Tariq M. Janjua
    • 1
  • Archie Defillo
    • 1
  • Penny Sinner
    • 1
  • Andrea Zelensky
    • 1
  1. 1.National Brain Aneurysm CenterSt. Joseph’s HospitalSt. PaulMinnesota
  2. 2.St. PaulMinneapolis

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