Recombinant factor VIIa

Massimo Franchini; Marco Zaffanello; Dino Veneri

doi:10.1160/TH05-01-0032

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(06): 1027-1035
DOI: 10.1160/TH05-01-0032

Review Article

Schattauer GmbH

Recombinant factor VIIa

An update on its clinical use

Massimo Franchini

¹Servizio di Immunoematologia e Trasfusione, Centro Emofilia, Azienda Ospedaliera di Verona, Verona, Italy

,

Marco Zaffanello

²Clinica Pediatrica, Divisione di Ematologia, Università di Verona, Verona, Italy

,

Dino Veneri

³Dipartimento di Medicina Sperimentale e Clinica, Divisione di Ematologia, Università di Verona, Verona, Italy

› Author Affiliations

Abstract

Summary

Recombinant activated factor VII (rFVIIa, Novo Seven^®) has been successfully used to treat bleeding episodes in patients with antibodies against coagulation factors VIII and IX. In recent years, rFVIIa has also been employed for the management of uncontrolled bleeding in a number of congenital and acquired haemos- tatic abnormalities. Based on a literature search, this review examines the current knowledge on therapy with rFVIIa, from the now well-standardized uses to the newer and less well-characterised clinical applications.

Keywords

Recombinant FVIIa - bleeding - haemophilia - inhibitors

Full Text

References

References
1 Lusher J, Ingerslev J, Roberts H. et al. Clinical experience with recombinant factor VIIa. Blood Coagul Fibrinolysis 1998; 9: 119-28.
2 Hedner U, Ingerslev J. Clinical use of recombinant FVIIa (rFVIIa). Transfus Sci 1998; 19: 163-76.
3 Nègrier C, Lienhart A. Overall experience with Novoseven®. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) suppl 19-24.
4 Kessler CM. New products for managing inhibitors to coagulation factors: a focus on recombinant factor VIIa concentrate. Curr Opin Hematol 2000; 7: 408-13.
5 Jurlander B, Thim L, Klausen NK. et al. Recombinant activated factor VII (rFVIIa): characterization, manufacturing and clinical development. Semin Thromb Hemost 2001; 27: 373-83.
6 Hedner U, Erhardtsen E. Potential role for rFVIIa in transfusion medicine. Transfusion 2002; 42: 114-24.
7 Uhlmann EJ, Eby CS. Recombinant activated factor VIII for non-hemophiliac bleeding patients. Curr Opin Hematol 2004; 11: 198-204.
8 Goodnough LT, Lublin DM, Zhang L. et al. Transfusion medicine service policies for recombinant factor VIIa administration. Transfusion 2004; 44: 1325-31.
9 Ghorashian S, Hunt BJ. “Off-license” use of recombinant activated factor VII. Blood Rev 2004; 18: 245-59.
10 Mathew P. The use of rFVIIa in non-haemophilia bleeding conditions in paediatrics. Thromb Haemost 2004; 92: 738-4.
11 Hedner U. Recombinant factor VIIa (Novo- Seven®) as a hemostatic agent. Dis Mon 2003; 49: 39-48.
12 Roberts HR, Monroe DM, White GC. The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood 2004; 104: 3858-64.
13 Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-65.
14 Hoffman M. A cell-based model of haemostasis. Blood Rev 2003; 17: S1-S5.
15 Monroe DM, Hoffman M, Oliver JA. et al. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol 1997; 99: 542-7.
16 Rauch U, Bonderman D, Badimon J. et al. Platelets become tissue factor positive during thrombus formation. Blood 1998; 92: 347a.
17 Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin- activatable fibrinolysis inhibitor. J Biol Chem 1995; 270: 14477-84.
18 Cawthern KM, van’t Veer C, Lock JB. et al. Blood coagulation in hemophilia A and hemophilia C. Blood 1998; 91: 4581-92.
19 Kjalke M, Ezban M, Monroe DM. et al. High-dose factor VIIa increases initial thrombin generation and mediates faster platelet activation in thrombocytopenia- like conditions in a cell-based model system. Br J Haematol 2001; 114: 114-20.
20 Hoffman M, Monroe DM 3rd. The action of highdose factor VIIa (FVIIa) in a cell-based model of hemostasis. Semin Hematol 2001; 38: 6-9.
21 Lisman T, Adelmeijer J, Heijnen HF. et al. Recombinant factor VIIa restores aggregation of alphaIIbbeta3- deficient platelets via tissue factor-independent fibrin generation. Blood 2004; 103: 1720-7.
22 Gabriel DA, Li X, Monroe DM 3rd. et al. Recombinant human factor VIIa (rFVIIa) can activate factor FIX on activated platelets. J Thromb Haemost 2004; 2: 1816-22.
23 Lisman T, De Groot PG. Mechanism of action of recombinant factor VIIa. J Thromb Haemost 2003; 1: 1138-9.
24 ten Cate H, Bauer KA, Levi M. et al. The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor. J Clin Invest 1993; 92: 1207-12.
25 van 't Veer C, Golden NJ, Mann KG. Inhibition of thrombin generation by the zymogen factor VII: implications for the treatment of hemophilia A by factor VIIa. Blood 2000; 95: 1330-5.
26 Butenas S, Brummel KE, Bouchard BA. et al. How factor VIIa works in hemophilia. J Thromb Haemost 2003; 1: 1158-60.
27 Butenas S, Brummel KE, Paradis SG. et al. Influence of factor VIIa and phospholipids on coagulation in “acquired” hemophilia. Arterioscler Thromb Vasc Biol 2003; 23: 123-9.
28 Lisman T, Mosnier LO, Lambert T. et al. Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A. Blood 2002; 99: 175-9.
29 Hedner U. Treatment of patients with factor VIII and factor IX inhibitors with special focus on the use of recombinant factor VIIa. Thromb Haemost 1999; 82: 531-9.
30 Hedner U, Glazer S, Pinkel K. et al. Successful use of rFVIIa in a patient with severe haemophilia A subjected to synovectomy. Lancet 1988; ii: 1193
31 Shapiro AD, Gilchrist GS, Keith Hoots WK. et al. Prospective, randomized trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery. Thromb Haemost 1998; 80: 773-8.
32 Lusher JM, Roberts HR, Davignon G. et al. A randomized, double blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. rFVIIa Study Group. Haemophilia 1998; 4: 790-8.
33 Key NS, Aledort LM, Beardsley D. et al. Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors. Thromb Haemost 1998; 80: 912-8.
34 Santagostino E, Gringeri A, Mannucci PM. Home treatment with recombinant activated factor VII in patients with factor VIII inhibitors: the advantages of early intervention. Br J Haematol 1999; 104: 22-6.
35 Laurian Y, Goudemand J, Negrier C. et al. Use of recombinant activated factor VII as first line therapy for bleeding episodes in hemophiliacs with factor VIII or IX inhibitors (NOSEPAC study). Blood Coagul Fibrinolysis 1998; 9: S155-S156.
36 Ingerslev J, Thykjaer H, Kudsk Jensen O. et al. Home treatment with recombinant activated factor VII: results from one center. Blood Coagul Fibrinolysis 1998; 9: S107-10.
37 Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004; 2: 899-909.
38 Ingerslev J, Freidman D, Gastineau D. et al. Major surgery in haemophilic patients with inhibitors using recombinant factor VIIa. Haemostasis 1996; 26 Suppl 118-23.
39 Key NS. Inhibitors in congenital coagulation disorders. Br J Haematol 2004; 127: 379-91.
40 Rodriguez-Merchan EC, Rocino A. Literature review of surgery management in inhibitor patients. Haemophilia 2004; 10 (Suppl. 20) Suppl 22-9.
41 Tagariello G, De Biasi E, Gajo GB. et al. Recombinant FVIIa continuous infusion and total hip replacement in patient with hemophilia and high titer of inhibitors to FVIII: experiences of two cases. Haemophilia 2000; 6: 581-3.
42 Schulman S, Bech-Jensen M, Varon D. et al. Feasibility of using recombinant factor VIIa in continuous infusion. Thromb Haemost 1996; 75: 432-6.
43 Ludlam CA, Smith MP, Morfini M. et al. A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation. Br J Haematol 2003; 120: 808-13.
44 Baudo F, Redaelli R, Caimi TM. et al. The continuous infusion of recombinant activated factor VIIa (rFVIIa) in patients with factor VIII inhibitors activates the coagulation and fibrinolytic systems without clinical complications. Thromb Res 2000; 99: 21-4.
45 Gringeri A. Relationship between factor VII activity and clinical efficacy of recombinant factor VIIa given by continuous infusion to patients with factor VIII inhibitors. Thromb Haemost 2001; 86: 954-8.
46 Mauser-Bunschoten EP, Goede-Bolder A, Wielenga JJ. et al. Continuous infusion of recombinant factor VIIa in patients with haemophilia and inhibitors. Experience in the Netherlands and Belgium. Neth J Med 1998; 53: 249-55.
47 Montoro JB, Altisent C, Pico M. et al. Recombinant factor VIIa in continuous infusion during central line insertion in a child with factor VIII high-titre inhibitor. Haemophilia 1998; 4: 762-5.
48 Mauser-Bunschoten EP, Koopman MM, Goede-Bolder AD. et al. The Recombinant Factor VIIa Data Collection Group. Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors. Haemophilia 2002; 8: 649-56.
49 Kenet G, Lubetsky A, Luboshitz J. et al. Treatment of inhibitor patients with rFVIIa: continuous infusion protocols as compared to a single, large dose. Haemophilia 2000; 6: 279a
50 Schulman S, D’Oiron R, Martinowitz U. et al. Experiences with continuous infusion of recombinant activated factor VII. Blood Coagul Fibrinolysis 1998; 9: S97-S101.
51 Smith MP, Ludlam CA, Collins PW. et al. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding. Thromb Haemost 2001; 86: 949-53.
52 McPherson J, Sutcharitchan P, Lloyd J. et al. Experience with continuous infusion of recombinant activated factor VII in the Asia-Pacific region. Blood Coagul Fibrinolysis 2000; 11: S31-S34.
53 Chuansumrit A, Isarangkura P, Angchaisuksiri P. et al. Controlling acute bleeding episodes with recombinant factor VIIa in haemophiliacs with inhibitor: continuous infusion and bolus injection. Haemophilia 2000; 6: 61-5.
54 Santagostino E, Morfini M, Rocino A. et al. Relationship between factor VII activity and clinical efficacy of recombinant factor VIIa given by continuous infusion to patients with factor VIII inhibitors. Thromb Haemost 2001; 86: 954-8.
55 Ewenstein BM. Continuous infusion of recombinant factor VIIa: continue or not?. Thromb Haemost 2001; 86: 942-4.
56 Kenet G, Lubetsky A, Luboshitz J. et al. A new approach to treatment of bleeding episodes in young hemophilia patients: a single bolus megadose of recombinant activated factor VII (NovoSeven ® ). J Thromb Haemost 2003; 1: 450-5.
57 Shapiro A. Inhibitor treatment: state of the art. Dis Mon 2003; 49: 22-38.
58 Key NS, Nelsestuen GL. Views on methods for monitoring recombinant factor VIIa in inhibitor patients. Sem Hematol 2004; 41: 51-4.
59 Sørensen 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: 102-10.
60 Gabriel DA, Carr M, Roberts HR. Monitoring coagulation and the clinical effects of recombinant factor VIIa. Sem Hematol 2004; 41: 20-4.
61 Arkin S, Blei F, Fetten J. et al. Human coagulation factor FVIIa (recombinant) in the management of limbthreatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use programme in patients with severe haemophilia or with acquired inhibitors. Blood Coagul Fibrinolysis 2000; 11: 255-9.
62 Von Depka M. NovoSeven: mode of action and use in acquired haemophilia. Intensive Care Med 2002; 28: S222-7.
63 Majundar G, Phillips JK, Lavallee H. et al. Acquired hemophilia in association with type III von Willebrand’s disease: successful treatment with high purity von Willebrand’s factor and recombinant factor VIIa. Blood Coagul Fibrinolysis 1993; 4: 1035
64 Shafi T, Jeha MT, Black L. et al. Severe acquired hemophilia A treated with recombinant factor VIIa. Br J Haematol 1997; 98: 910-2.
65 Maliekel K, Rana N, Green D. Recombinant factor VIIa in the management of a pseudotumor in acquired haemophilia. Haemophilia 1997; 3: 54-8.
66 Papadaki HA, Xylouri I, Valatas W. et al. Severe acquired hemophilia A successfully treated with activated recombinant human factor VII. Ann Hematol 1998; 77: 123-5.
67 Liebman HA, Chediak J, Fink KI. et al. Activated recombinant human coagulation factor VII (rFVIIa) therapy for abdominal bleeding in patients with inhibitory antibodies to factor VIII. Am J Hematol 200 63: 109-13.
68 Franchini M, Girelli D, Olivieri O. et al. Clinical heterogeneity of acquired hemophilia A: a description of 4 cases. Haematologica 2005; 90: ECR16
69 Hay CRM, Negrier C, Ludlam CA. The treatment of bleeding in acquired haemophilia with recombinant factor VIIa: a multicentre study. Thromb Haemost 1997; 79: 1463-7.
70 Baudo F, de Cataldo F, Gaidano G. Treatment of acquired factor VIII inhibitor with recombinant activated factor VIIa: data from the Italian registry of acquired hemophilia. Haematologica 2004; 88: 759-61.
71 Perry DJ. Factor VII deficiency. Blood Coagul Fibrinolyisis 2003; 14 (Suppl. 01) suppl S47-54.
72 Mariani G, Mannucci PM, Mazzucconi MG. et al. Treatment of congenital factor VII deficiency with a new concentrate. Thromb Haemost 1978; 39: 675-82.
73 Dike GW, Griffiths D, Bidwell E. et al. A factor VII concentrate for therapeutic use. Br J Haematol 1980; 45: 107-18.
74 Billio A, Pescosta N, Rosanelli C. et al. Successful short term oral surgery prophylaxis with rFVIIa in severe congenital factor VII deficiency. Blood Coagul Fibrinolysis 1997; 8: 249-50.
75 Mariani G, Testa MG, Di Paolantonio T. et al. Use of recombinant, activated factor VII in the treatment of congenital factor VII deficiencies. Vox Sang 1999; 77: 131-6.
76 Wong WY, Huang WC, Miller R. et al. Clinical efficacy and recovery levels of recombinant FVIIa (NovoSeven) in the treatment of intracranial hemorrhage in severe neonatal FVII deficiency. Haemophilia 2000; 6: 50-4.
77 Weei-Yuarn H, Kruskall MS, Bauer KA. et al. The use of recombinant activated factor VII in three patients with central nervous system hemorrhages associated with factor VII deficiency. Transfusion 2004; 44: 1562-6.
78 Scharrer I. Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency. Haemophilia 1999; 5: 253-9.
79 Ingerslev J, Knudsen L, Hvid I. et al. Use of recombinant factor VIIa in surgery in factor VII deficient patients. Haemophilia 1997; 3: 215-8.
80 Tcheng WY, Donkin J, Konzal S. et al. Recombinant factor VIIa prophylaxis in a patient with severe congenital factor VII deficiency. Haemophilia 2004; 10: 295-8.
81 Mathijssen NC, Masereeuw R, Verbeek K. et al. Prophylactic effect of recombinant factor VIIa in factor VII deficient patients. Br J Haematol 2004; 125: 494-9.
82 Laurian Y. Treatment of bleeding in patients with platelet disorders: is there a place for recombinant factor VIIa?. Pathophysiol Haemost Thromb 2002; 32: 37-40.
83 Goodnough LT. Experiences with recombinant human factor VIIa in patients with thrombocytopenia. Semin Hematol 2004; 41 (Suppl. 01) suppl 25-9.
84 Kristensen J, Killander A, Hippe E. et al. Clinical experience with recombinant factor VIIa in patients with thrombocytopenia. Haemostasis 1996; 26 (Suppl. 01) suppl 159-64.
85 Vidarsson B, Onundarson PT. Recombinant factor VIIa for bleeding in refractory thrombocytopenia. Thromb Haemost 2000; 83: 634-5.
86 Gerotziafas GT, Zervas C, Gavrielidis G. et al. Effective hemostasis with rFVIIa treatment in two patients with severe thrombocytopenia and life-threatening hemorrhage. Am J Hematol 2002; 69: 219-22.
87 Chuansumrit A, Sangkapreecha C, Hathirat P. Successful epistaxis control in a patient with Glanzmann thrombasthenia by increased bolus injection dose of recombinant factor VIIa. Thromb Haemost 1999; 82: 1778
88 Poon MC, Demers C, Jobin F. et al. Recombinant factor VIIa is effective for bleeding and surgery in patients with Glanzmann thrombasthenia. Blood 1999; 94: 3951-3.
89 Tengborn L, Petruson B. A patient with Glanzmann thrombasthenia and epistaxis successfully treated with recombinant factor VIIa. Thromb Haemost 1996; 75: 981-2.
90 Poon MC, d'Oiron R. Recombinant activated factor VII (NovoSeven) treatment of platelet-related bleeding disorders. International Registry on Recombinant Factor VIIa and Congenital Platelet Disorders Group. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) Suppl S55-68.
91 Caglar K, Cetinkaya A, Aytac S. et al. Use of recombinant factor VIIa for bleeding in children with Glanzmann thrombasthenia. Pediatr Hematol Oncol 2003; 20: 435-8.
92 Chuansumrit A. Confirmation of high dose recombinant factor VIIa in treating patients with Glanzmann thrombasthenia. J Thromb Haemost 2003; 1: 396.
93 Chuansumrit A, Suwannuraks M, Sri-Udomporn N. et al. Recombinant activated factor VII combined with local measures in preventing bleeding from invasive dental procedures in patients with Glanzmann thrombasthenia. Blood Coagul Fibrinolysis 2003; 14: 187-90.
94 Poon MC, d'Oiron R, Hann I. et al. Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia. Semin Hematol 2001; 38: 21-5.
95 Almeida A, Khair K, Hann I. et al. The use of recombinant factor VIIa in children with inherited platelet function disorders. Br J Haematol 2003; 121: 477-81.
96 Peters M, Heijboer H. Treatment of a patient with Bernard-Soulier syndrome and recurrent nosebleeds with recombinant factor VIIa. Thromb Haemost 1998; 80: 352
97 Fressinaud E, Sigaud-Fiks M, Le Boterff C. et al. Use of recombinant factor VIIa (NovoSeven®) for dental extraction in a patient affected by platelet-type (pseudo-) von Willebrand disease. Haemophilia 1998;: XXIIIth Congress of the World Federation of Hemophilia (abstract).
98 Poon MC, Katsarou O, Huth-Kuehne A et al. Recombinant factor VIIa in congenital platelet bleeding disorders. American Society of Hematology 2000, 1–5 December, San Francisco. Blood; 96(suppl 1): 256a (abstract).
99 Rapaport SI. Coagulation problems in liver disease. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) (Suppl) S69-74.
100 Caldwell SH, Chang C, Macik BG. Recombinant activated factor VII (rFVIIa) as a hemostatic agent in liver disease: a break from convention in need of controlled trials. Hepatology 2004; 39: 592-8.
101 Bernstein DE, Jeffers L, Erhardtsen E. et al. Recombinant factor VIIa corrects prothrombin time i cirrhotic patients: a preliminary study. Gastroenterology 1997; 113: 1930-7.
102 Jeffers L, Chalasani N, Balart L. et al. Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy. Gastroenterology 2002; 123: 118-26.
103 Bosch J, Thabut D, Bendtsen F. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004; 127: 1123-30.
104 Ejlersen E, Melsen T, Ingerslev J. et al. Recombinant activated factor VII (rFVIIa) acutely normalizes prothrombin time in patients with cirrhosis during bleeding from oesophageal varices. Scand J Gastroenterol 2001; 10: 1081-5.
105 Romero-Castro R, Jimenez-Saenz M, Pellicer-Bautista F. et al. Recombinant activated factor VII as hemostatic therapy in eight cases of severe hemorrhage from esophageal varices. Clinical Gastroenterol Hepatol 2004; 2: 78-84.
106 O’Connell NM, Perry DJ, Hodgson AJ. et al. Recombinant FVIIa in the management of uncontrolled hemorrhage. Transfusion 2003; 43: 1711-6.
107 Shami VM, Caldwell SH, Hespendeide EE. et al. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl 2003; 9: 138-43.
108 Kalicinski P, Kaminski A, Drewniak T. et al. Quick correction of hemostasis in two patients with fulminant liver failure undergoing liver transplantation by recombinant activated factor VII. Transplant Proc 1999; 31: 378-9.
109 Hendriks HG, Meijer K, de Wolf JT. et al. Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study. Transplantation 2001; 71: 402-5.
110 Meijer K, Hendriks HGD, de Wolf JTM. et al. Recombinant factor VIIa in orthotopic liver transplantation: influence on parameters of coagulation and fibrinolysis. Blood Coagul Fibrinolysis 2003; 14: 169-74.
111 Planinsic RM, Emre S. et al. Safety and efficacy of single bolus dose of recombinant factor VIIa in patients undergoing orthotopic liver transplantation: a randomized multi-center study. Hepatology 2002; 36: 660A
112 Grounds M. Recombinant factor VIIa (rFVIIa) and its use in severe bleeding in surgery and trauma: a review. Blood Reviews 2003; 17: S11-S21.
113 Kenet G, Walden R, Eldad A. et al. Treatment of traumatic bleeding with recombinant factor VIIa. Lancet 1999; 354: 1879
114 Martinowitz U, Holcomb JB, Pusateri AE. et al. Intravenous rFVIIa administered for haemorrhage control in hypothermic coagulopathic swine with grade V liver injuries. J Trauma 2001; 50: 721-9.
115 Mayo A, Misgav M, Kluger Y. et al. Recombinant activated factor VII (Novoseven): addition to replacement therapy in acute, uncontrolled and life-threatening bleeding. Vox Sang 2004; 87: 34-40.
116 Martinowitz U, Kenet G, Segal E. et al. Recombinant activated factor VII for adjunctive haemorrhage control in adults. J Trauma 2001; 51: 431-9.
117 O’Neill PA, Bluth M, Gloster ES. et al. Successful use of recombinant activated factor VII for trauma-associated haemorrhage in a patient without preexisting coagulopathy. J Trauma 2002; 52: 400-5.
118 Kamphuisen PW, van den Akker JM, Kaasjager KAH. Control of life-threatening pulmonary bleeding with activated recombinant factor VII. Am J Med 2002; 112: 332-3.
119 Svartholm E, Annerhagen V, Lanne T. Treatment of bleeding in severe necrotising pancreatitis with recombinant factor VIIa. Anesthesiology 2002; 96: 1528
120 Aggarwal A, Catlett J, Alcorn K. The use of recombinant factor VIIa in the management of intractable bleeding in surgical and trauma patients. American Society of Hematology Presentation, 43rd Annual Meeting, Orlando; December 2001 [Abstract 3883].
121 Bouwmeester FW, Jonjhoff AR, Verheijen RHM. et al. Successful treatment of life-threatening post partum haemorrhage with recombinant activated factor VII. Obstet Gynaecol 2003; 101: 1174-6.
122 Boehlen F, Morales MA, Fontana P. et al. Prolonged treatment of massive postpartum haemorrhage with recombinant factor VIIa: case report and review of the literature. Br J Obstet Gynaecol 2004; 111: 284-7.
123 Ng HJ, Koh LP, Lee LH. Successful control of postsurgical bleeding by recombinant factor VIIa in a renal failure patient given low molecular weight heparin and aspirin. Ann Hematol 2003; 82: 257-8.
124 Al Douri M, Shafi T, Al Khudairi D. et al. Effect of the administration of recombinant activated factor VII (rFVIIa; Novoseven) in the management of severe uncontrolled bleeding in patients undergoing heart valve replacement surgery. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) (Suppl1) S121-7.
125 Hendriks HGD, van der Maaten JMAA, de Wolf J. et al. An effective treatment of severe intractable bleeding after heart valve repair by one single dose of activated recombinant factor VII. Anesth Analg 2001; 93: 287-9.
126 Karkouti K, Beattie WS, Wijeysundera DN. et al. Recombinant factor VIIa for intractable blood loss after cardiac surgery: a propensity score-matched case-control analysis. Transfusion 2005; 45: 26-34.
127 Zietkiewitcz M, Garlicki M, Domagala J. et al. Successful use of rFVIIa to control bleeding abnormalities in a patient with a left ventricular assist device. J Thorac Cardiovasc Surg 2002; 123: 384-5.
128 Potapov EV, Pasic M, Bauer M. et al. Activated recombinant factor VII for control of diffuse bleeding after implantation of ventricular assist device. Ann Thorac Surg 2002; 74: 2182-3.
129 Friederich PW, Henny CP, Messelink EJ. et al. The effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet 2003; 361: 201-5.
130 White B, McHale J, Ravi N. et al. Successful use of recombinant FVIIa (Novoseven) in the management of intractable post-surgical intra-abdominal haemorrhage. Br J Haematol 1999; 107: 677-8.
131 Vlot AJ, Ton E, Mackaay AJC. et al. Treatment of a severely bleeding patient without preexisting coagulopathy with activated recombinant factor VII. Am J Med 2000; 108: 421-2.
132 Lodge P, Jonas S, Jaeck D et al. Recombinant factor VIIa (NovoSeven ® ) in partial hepatectomy: a randomized, placebo-controlled, double blind clinical trial. Presented at the American Association for the Study of Liver Diseases Annual Meeting, Boston, Nov 2002. Abstract 177.
133 Park P, Fewel ME, Garton HJ. et al. Recombinant activated factor VII for the rapid correction of coagulopathy in nonhemophiliac neurosurgical patients. Neurosurgery 2003; 53: 34-9.
134 Dietrich W, Spannagl M. Caveat against the use of activated recombinant factor VII for intractable bleeding in cardiac surgery. Anesth Analg 2001; 94: 1369-71.
135 Ciavarella N, Schiavoni M, Valenzano E. et al. Use of recombinant factor VIIa in the treatment of two patients with type III von Willebrand’s disease and an inhibitor against the von Willebrand factor. Haemostasis 1996; 26: 150-4.
136 Billon S, Niger CL, Escoffre-Barbe M. et al. The use of recombinant factor VIIa (NovoSeven) in a pa- tient with a factor XI deficiency and a circulating anticoagulant. Blood Coagul Fibrinolysis 2001; 12: 551-3.
137 Hedner U. Factor VIIa in the treatment of haemophilia. Blood Coagul Fibrinolysis 1990; 1: 307-17.
138 Lawler P, White B, Pye S. et al. Successful use of recombinant factor VIIa in a patient with inhibitor secondary to severe factor XI deficiency. Haemophilia 2002; 8: 145-8.
139 Bern MM, Sahud M, Zhukov O. et al. Treatment of factor XI inhibitor using recombinant activated factor VIIa. Haemophilia 2005; 11: 20-5.
140 O’Connell NM. Factor XI deficiency. Sem Hematol 2004; 41: 76-81.
141 Waddington DP, McAuley FT, Hanley JP. et al. The use of recombinant factor VIIa in a Jehovah's witness with auto-immune thrombocytopenia and postsplenectomy haemorrhage. Br J Haematol 2002; 119: 286-8.
142 Mindikoglu AL, Anantharaju A, George M. et al. Splenic embolization in a Jehovah's Witness: role of recombinant human factor VIIa. Hepatogastroenterology 2003; 50: 1697-9.
143 Virchis A, Hughes C, Berney S. Severe gastrointestinal haemorrhage responding to recombinant factor VIIa in a Jehovah's Witness with refractory immune thrombocytopenia. Hematol J 2004; 5: 281-2.
144 Tanaka KA, Waly AA, Cooper WA. et al. Treatment of excessive bleeding in Jehovah's Witness patients after cardiac surgery with recombinant factor VIIa (NovoSeven). Anesthesiology 2003; 98: 1513-5.
145 Blatt J, Gold SH, Wiley JM. et al. Off-label use of recombinant factor VIIa in patients following bone marrow transplantation. Bone Marrow Transplant 2001; 28: 405-7.
146 de Fabritiis P, Dentamaro T, Picardi A. et al. Recombinant factor VIIa for the management of severe hemorrhages in patients with hematologic malignancies. Haematologica 2004; 89: 243-5.
147 Hicks K, Peng D, Gajewski JL. Treatment of diffuse alveolar hemorrhage after allogeneic bone marrow transplant with recombinant factor VIIa. Bone Marrow Transplant 2002; 30: 975-8.
148 Diness V, Lund-Hansen T, Hedner U. Effects of recombinant human FVIIa on warfarin-induced bleeding in rats. Thrombosis Res 1990; 59: 921-9.
149 Erhardtsen E, Nony P, Dechavanne M. et al. The effect of recombinant factor VIIa (NovoSeven™) in healthy volunteers receiving acenocoumarol to an International International Normalised Ratio above 2.0. Blood Coagul Fibrinolysis 1998; 9: 741-8.
150 Berntorp E, Stigendal L, Lethagen S. et al. Novo- Seven in warfarin-treated patients. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) (Suppl) S113-5.
151 Deveras RAE, Kessler CM. Reversal of warfarininduced excessive anticoagulation with recombinant factor VIIa concentrate. Ann Intern Med 2002; 137: 884-8.
152 Sorensen B, Johansen P, Nielsen GL. et al. 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.
153 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.
154 Udvardy M, Telek B, Mezey G. et al. Successful control of massive coumarol-induced acute upper gastrointestinal bleeding and correction of prothrombin time by recombinant active factor VII (Eptacog alpha, NovoSeven) in a patient with a prosthetic aortic valve and two malignancies (chronic lymphoid leukemia and lung cancer). Blood Coagul Fibrinolysis 2004; 15: 265-7.
155 Rice KM, Savidge GF. Novoseven ® (recombinant factor VIIa) in central nervous system bleeds. Haemostasis 1996; 26 (Suppl. 01) (Suppl) 131-4.
156 Tobias JD. Synthetic factor VIIa to treat dilutional coagulopathy during posterior spinal fusion in two children. Anesthesiology 2002; 96: 1522-5.
157 Mayer SA, Brun NC, Broderick J et al. Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage. Stroke 2004 Nov 29; [Epub ahead of print].
158 Greisen G, Andreasen AB. Recombinant factor VIIa in preterm neonates with prolonged prothrombin time. Blood Coagul Fibrinolysis 2003; 14: 117-20.
159 Bianchi A, Jackson D, Maitz P. et al. Treatment of bleeding with recombinant factor VIIa in a patient with extensive burns. Thromb Haemost 2004; 91: 203-4.
160 Revesz T, Arets B, Bierings M. et al. Recombinant factor VIIa in severe uremic bleeding. Thromb Haemost 1998; 80: 353
161 Hay CRM. Thrombosis and recombinant factor VIIa. J Thromb Haemost 2004; 2: 1698-9.
162 Aledort LM. Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity. J Thromb Haemost 2004; 2: 1700-8.
163 Roberts HS, Monroe III DM, Hoffman M. Safety profile of recombinant factor VIIa. Sem Hematol 2004; 1 (Suppl. 01) (Suppl) 101-8.
164 Guillet B, Pinganaud C, Proulle V. et al. Myocardial infarction occurring in a case of acquired haemophilia during the treatment course with recombinant activated factor VII. Thromb Haemost 2002; 88: 698-9.
165 Peerlink K, Vermylen J. Acute myocardial infarction following administration of recombinant activated factor VII (NovoSeven) in a patient with haemophilia A and inhibitor. Thromb Haemost 1999; 82: 1775-6.
166 Bui JD, Despotis GD, Trulock EP. et al. Fatal thrombosis after administration of activated prothrombin complex concentrates in a patient supported by extracorporeal membrane oxygenation who had received activated recombinant factor VII. J Thorac Cardiovasc Surg 2002; 124: 852-4.
167 O’Connell NM. Factor XI deficiency: from molecular genetics to clinical management. Blood Coagul Fibrinolysis 2003; 14 (Suppl. 01) (Suppl.) S59-64.
168 Pickard JD, Kirkpatrick PJ, Melsen T. et al. Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) (Suppl) S117-20.
169 d’Oiron R, Menart C, Trzeciak MC. et al. Use of recombinant factor VIIa in 3 patients with inherited type I Glanzmann’s thrombasthenia undergoing invasive procedures. Thromb Haemost 2000; 83: 644-7.
170 Laffan M, O'Connell NM, Perry DJ. et al. Analysis and results of the recombinant factor VIIa extended-use registry. Blood Coagul Fibrinolysis 2003; 14 (Suppl. 01) (Suppl) S35-8.
171 Kohler M. Thrombogenicity of prothrombin complex concentrates. Thromb Res 1999; 95: S13-17.
172 Ehrlich HJ, Henzl MJ, Gomperts ED. Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events. Haemophilia 2002; 8: 83-90.