Optimal Use of Recombinant Factor VIIa in the Control of Bleeding Episodes in Hemophilic Patients

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2010 Aug 7

PMID 20689699

Citations 2

Authors

John Puetz

Affiliations

Soon will be listed here.

Abstract

One of the last remaining clinical hurdles in the treatment of people with hemophilia is the development of inhibitors. Alloantibodies or autoantibodies directed at coagulation factors render the infusion of coagulation factor concentrates ineffective, and alternative means must be used to achieve hemostasis. Recombinant factor VIIa (rFVIIa) was developed to control bleeding episodes in hemophilic patients with inhibitors. Clinical efficacy in achieving hemostasis in inhibitor patients was demonstrated by a compassionate-use protocol, as well as in randomized controlled trials. To date, over 1.5 million doses of rFVIIa have been given to inhibitor patients, with an excellent efficacy and safety record. Because of its short half-life, alternative means of dosing and infusing rFVIIa have been explored and are reviewed here.

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References

Goldstein B, Geldziler B, Bjerre J, Seremetis S . Evidence-based use of recombinant FVIIa (NovoSeven, NiaStase) for the treatment of hemophilia with inhibitors in children and adolescents. Transfus Apher Sci. 2008; 38(1):25-32. DOI: 10.1016/j.transci.2007.12.002. View

Mauser-Bunschoten E, Koopman M, Leebeek F, van der Meer J, van Marwijk Kooij G, van der Linden P . Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors. Haemophilia. 2002; 8(5):649-56. DOI: 10.1046/j.1365-2516.2002.00667.x. View

Smith M, Ludlam C, Collins P, Hay C, Wilde J, Grigeri A . 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(4):949-53. View

Gringeri A, Santagostino E, Mannucci P . Failure of recombinant activated factor VII during surgery in a hemophiliac with high-titer factor VIII antibody. Haemostasis. 1991; 21(1):1-4. DOI: 10.1159/000216194. View

Butenas S, Brummel K, Branda R, Paradis S, Mann K . Mechanism of factor VIIa-dependent coagulation in hemophilia blood. Blood. 2002; 99(3):923-30. DOI: 10.1182/blood.v99.3.923. View

Feldman B, Pai M, Rivard G, Israels S, Poon M, Demers C . Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study. J Thromb Haemost. 2006; 4(6):1228-36. DOI: 10.1111/j.1538-7836.2006.01953.x. View

Shapiro A . Inhibitor treatment: state of the art. Semin Hematol. 2001; 38(4 Suppl 12):26-34. DOI: 10.1016/s0037-1963(01)90144-1. View

Fay P . Factor VIII structure and function. Int J Hematol. 2006; 83(2):103-8. DOI: 10.1532/IJH97.05113. View

Yatuv R, Dayan I, Carmel-Goren L, Robinson M, Aviv I, Goldenberg-Furmanov M . Enhancement of factor VIIa haemostatic efficacy by formulation with PEGylated liposomes. Haemophilia. 2008; 14(3):476-83. DOI: 10.1111/j.1365-2516.2008.01741.x. View

10.

Roberts H, Monroe D, White G . The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood. 2004; 104(13):3858-64. DOI: 10.1182/blood-2004-06-2223. View

11.

Hoots W . Challenges in the therapeutic use of a "so-called" universal hemostatic agent: recombinant factor VIIa. Hematology Am Soc Hematol Educ Program. 2006; :426-31. DOI: 10.1182/asheducation-2006.1.426. View

12.

Johansson P . Off-label use of recombinant factor VIIa for treatment of haemorrhage: results from randomized clinical trials. Vox Sang. 2008; 95(1):1-7. DOI: 10.1111/j.1423-0410.2008.01063.x. View

13.

Vincent J, Rossaint R, Riou B, Ozier Y, Zideman D, Spahn D . Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding--a European perspective. Crit Care. 2006; 10(4):R120. PMC: 1750973. DOI: 10.1186/cc5026. View

14.

Hedner U, Kisiel W . Use of human factor VIIa in the treatment of two hemophilia A patients with high-titer inhibitors. J Clin Invest. 1983; 71(6):1836-41. PMC: 370389. DOI: 10.1172/jci110939. View

15.

Bonde C, Jensen M . Continuous infusion of recombinant activated factor VII: stability in infusion pump systems. Blood Coagul Fibrinolysis. 1998; 9 Suppl 1:S103-5. View

16.

Hoots W, Ebbesen L, Konkle B, Auerswald G, Roberts H, Weatherall J . Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors. Haemophilia. 2008; 14(3):466-75. DOI: 10.1111/j.1365-2516.2008.01654.x. View

17.

Manco-Johnson M, Abshire T, Shapiro A, Riske B, Hacker M, Kilcoyne R . Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007; 357(6):535-44. DOI: 10.1056/NEJMoa067659. View

18.

Young G, McDaniel M, Nugent D . Prophylactic recombinant factor VIIa in haemophilia patients with inhibitors. Haemophilia. 2005; 11(3):203-7. DOI: 10.1111/j.1365-2516.2005.01096.x. View

19.

Moss J, Scharling B, Ezban M, Moller Sorensen T . Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects. J Thromb Haemost. 2009; 7(2):299-305. DOI: 10.1111/j.1538-7836.2008.03253.x. View

20.

Chuansumrit A, Srimuninnimit V, Juntarukha R . A single high dose of recombinant factor VIIa combining adjuvant therapy for controlling bleeding episodes in haemophiliacs with inhibitors. Haemophilia. 2001; 7(5):532-4. DOI: 10.1046/j.1365-2516.2001.0537a.x. View