FVIIa as therapeutic agent in hemophilia and beyond.
(2012) In Frontiers in Bioscience (Elite Edition) 4. p.1210-1223- Abstract
- Around 20percent of the patients with severe hemophilia develop inhibitory antibodies against the factor they lack. In these patients the administration of FVIII/FIX-concentrates are not hemostatically effective. Since FVIIa is not enzymatically active unless complexed with tissue factor (TF) exposed following an injury to the vessel wall, it was considered an attractive candidate for improved treatment of patients with inhibitors. Plasma-derived FVIIa was purified and shown to induce hemostasis in two hemophilia A patients with inhibitors. Later recombinant FVIIa (rFVIIa) was developed and pharmacological doses have an efficacy rate of around 90percent in serious bleedings and permit major orthopaedic surgery. These findings were a... (More)
- Around 20percent of the patients with severe hemophilia develop inhibitory antibodies against the factor they lack. In these patients the administration of FVIII/FIX-concentrates are not hemostatically effective. Since FVIIa is not enzymatically active unless complexed with tissue factor (TF) exposed following an injury to the vessel wall, it was considered an attractive candidate for improved treatment of patients with inhibitors. Plasma-derived FVIIa was purified and shown to induce hemostasis in two hemophilia A patients with inhibitors. Later recombinant FVIIa (rFVIIa) was developed and pharmacological doses have an efficacy rate of around 90percent in serious bleedings and permit major orthopaedic surgery. These findings were a breakthrough in understanding the FVII-TF pathway in hemostasis. The initially formed FVIIa-TF complexes provide a limited amount of thrombin, activating FVIII, FV, FXI as well as platelets. On the activated platelet surface the full burst of thrombin necessary for generating a firm fibrin hemostatic plug occurs. In case of impaired thrombin generation, loose fibrin plugs easily dissolved are formed. Extra rFVIIa enhances thrombin generation and generates tight fibrin plugs. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2273505
- author
- Hedner, Ulla LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Frontiers in Bioscience (Elite Edition)
- volume
- 4
- pages
- 1210 - 1223
- publisher
- Frontiers in Bioscience
- external identifiers
-
- pmid:22201947
- scopus:84860857377
- ISSN
- 1945-0508
- 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
- 1cfe537a-a4ed-4438-8907-5307da5ed8e6 (old id 2273505)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22201947?dopt=Abstract
- date added to LUP
- 2016-04-04 08:56:48
- date last changed
- 2022-05-16 22:34:00
@article{1cfe537a-a4ed-4438-8907-5307da5ed8e6,
abstract = {{Around 20percent of the patients with severe hemophilia develop inhibitory antibodies against the factor they lack. In these patients the administration of FVIII/FIX-concentrates are not hemostatically effective. Since FVIIa is not enzymatically active unless complexed with tissue factor (TF) exposed following an injury to the vessel wall, it was considered an attractive candidate for improved treatment of patients with inhibitors. Plasma-derived FVIIa was purified and shown to induce hemostasis in two hemophilia A patients with inhibitors. Later recombinant FVIIa (rFVIIa) was developed and pharmacological doses have an efficacy rate of around 90percent in serious bleedings and permit major orthopaedic surgery. These findings were a breakthrough in understanding the FVII-TF pathway in hemostasis. The initially formed FVIIa-TF complexes provide a limited amount of thrombin, activating FVIII, FV, FXI as well as platelets. On the activated platelet surface the full burst of thrombin necessary for generating a firm fibrin hemostatic plug occurs. In case of impaired thrombin generation, loose fibrin plugs easily dissolved are formed. Extra rFVIIa enhances thrombin generation and generates tight fibrin plugs.}},
author = {{Hedner, Ulla}},
issn = {{1945-0508}},
language = {{eng}},
pages = {{1210--1223}},
publisher = {{Frontiers in Bioscience}},
series = {{Frontiers in Bioscience (Elite Edition)}},
title = {{FVIIa as therapeutic agent in hemophilia and beyond.}},
url = {{http://www.ncbi.nlm.nih.gov/pubmed/22201947?dopt=Abstract}},
volume = {{4}},
year = {{2012}},
}