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FVIIa as therapeutic agent in hemophilia and beyond.

Hedner, Ulla LU (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)
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Contribution to journal
publication status
published
subject
in
Frontiers in Bioscience (Elite Edition)
volume
4
pages
1210 - 1223
publisher
Frontiers
external identifiers
  • pmid:22201947
  • scopus:84860857377
ISSN
1945-0508
language
English
LU publication?
yes
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
2012-01-03 21:33:17
date last changed
2017-01-01 07:41:29
@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},
  series       = {Frontiers in Bioscience (Elite Edition)},
  title        = {FVIIa as therapeutic agent in hemophilia and beyond.},
  volume       = {4},
  year         = {2012},
}