First 20 years with recombinant FVIIa (NovoSeven).
(2011) In Haemophilia 17. p.172-182- Abstract
- Summary. This review describes the background for the development of recombinant FVIIa (rFVIIa; NovoSeven) for use in haemophilic patients with inhibitors. The first proof of principle for using pharmacological doses of FVIIa as a haemostatic agent was obtained by producing small amounts of pure plasma-derived FVIIa, which showed encouraging effect in two patients with haemophilia A and inhibitors. To make pure FVIIa available for use in a larger number of patients, rFVIIa was produced that was approved for use in patients with inhibitors against coagulation factors (congenital haemophilia and acquired haemophilia) in 1996 (EU), 1999 (USA) and 2000 (Japan). The efficacy rate in severe bleedings and in major surgery including major... (More)
- Summary. This review describes the background for the development of recombinant FVIIa (rFVIIa; NovoSeven) for use in haemophilic patients with inhibitors. The first proof of principle for using pharmacological doses of FVIIa as a haemostatic agent was obtained by producing small amounts of pure plasma-derived FVIIa, which showed encouraging effect in two patients with haemophilia A and inhibitors. To make pure FVIIa available for use in a larger number of patients, rFVIIa was produced that was approved for use in patients with inhibitors against coagulation factors (congenital haemophilia and acquired haemophilia) in 1996 (EU), 1999 (USA) and 2000 (Japan). The efficacy rate in severe bleedings and in major surgery including major orthopaedic surgery has been found to be around 90% in controlled studies, and no serious safety concerns have been demonstrated. The availability of rFVIIa has facilitated the performance of elective major surgery in haemophilia patients with inhibitors. Further steps along the vision of providing a treatment for inhibitor patients similar to non-inhibitor patients have been the efficacy of rFVIIa in home-treatment and recently the encouraging experience in prophylaxis. The concept of using pharmacological doses of rFVIIa as a haemostatic agent is a new one, which has caused difficulties in finding the correct dose. A step forward has been the demonstration that similar efficacy can be achieved after one single dose of 270 mug kg(-1) instead of three injections of a dose of 90 mug kg(-1). The higher clearance rate in children suggests that higher doses may be beneficial in children. The availability of rFVIIa has made advances in the understanding of coagulation processes possible. In a cell-based in vitro model, it has been shown that rFVIIa binds to preactivated platelets if present in concentrations of 30 nm or higher. By doing so, it activates FX into FXa and enhances the thrombin generation on the activated platelet surface in the absence of FVIII/FIX. Through the increased thrombin generation, a firm, well-structured fibrin haemostatic plug, which is resistant to premature lysis, is formed. By exploiting this mechanism of action, rFVIIa may also be effective in situations other than haemophilia, characterized by an impaired thrombin generation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1645235
- author
- Hedner, Ulla LU and Lee, C A
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Haemophilia
- volume
- 17
- pages
- 172 - 182
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000285762900037
- pmid:20609014
- scopus:79951933686
- pmid:20609014
- ISSN
- 1351-8216
- DOI
- 10.1111/j.1365-2516.2010.02352.x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200)
- id
- cc48c9f1-97aa-461f-975b-2715ef4ff3fb (old id 1645235)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20609014?dopt=Abstract
- date added to LUP
- 2016-04-04 08:01:25
- date last changed
- 2022-08-23 03:30:18
@article{cc48c9f1-97aa-461f-975b-2715ef4ff3fb,
abstract = {{Summary. This review describes the background for the development of recombinant FVIIa (rFVIIa; NovoSeven) for use in haemophilic patients with inhibitors. The first proof of principle for using pharmacological doses of FVIIa as a haemostatic agent was obtained by producing small amounts of pure plasma-derived FVIIa, which showed encouraging effect in two patients with haemophilia A and inhibitors. To make pure FVIIa available for use in a larger number of patients, rFVIIa was produced that was approved for use in patients with inhibitors against coagulation factors (congenital haemophilia and acquired haemophilia) in 1996 (EU), 1999 (USA) and 2000 (Japan). The efficacy rate in severe bleedings and in major surgery including major orthopaedic surgery has been found to be around 90% in controlled studies, and no serious safety concerns have been demonstrated. The availability of rFVIIa has facilitated the performance of elective major surgery in haemophilia patients with inhibitors. Further steps along the vision of providing a treatment for inhibitor patients similar to non-inhibitor patients have been the efficacy of rFVIIa in home-treatment and recently the encouraging experience in prophylaxis. The concept of using pharmacological doses of rFVIIa as a haemostatic agent is a new one, which has caused difficulties in finding the correct dose. A step forward has been the demonstration that similar efficacy can be achieved after one single dose of 270 mug kg(-1) instead of three injections of a dose of 90 mug kg(-1). The higher clearance rate in children suggests that higher doses may be beneficial in children. The availability of rFVIIa has made advances in the understanding of coagulation processes possible. In a cell-based in vitro model, it has been shown that rFVIIa binds to preactivated platelets if present in concentrations of 30 nm or higher. By doing so, it activates FX into FXa and enhances the thrombin generation on the activated platelet surface in the absence of FVIII/FIX. Through the increased thrombin generation, a firm, well-structured fibrin haemostatic plug, which is resistant to premature lysis, is formed. By exploiting this mechanism of action, rFVIIa may also be effective in situations other than haemophilia, characterized by an impaired thrombin generation.}},
author = {{Hedner, Ulla and Lee, C A}},
issn = {{1351-8216}},
language = {{eng}},
pages = {{172--182}},
publisher = {{Wiley-Blackwell}},
series = {{Haemophilia}},
title = {{First 20 years with recombinant FVIIa (NovoSeven).}},
url = {{http://dx.doi.org/10.1111/j.1365-2516.2010.02352.x}},
doi = {{10.1111/j.1365-2516.2010.02352.x}},
volume = {{17}},
year = {{2011}},
}