History of rFVIIa therapy.
(2010) In Thrombosis Research 125 Suppl 1. p.4-6- Abstract
- Hemophilia patients with inhibitors against FVIII/FIX present with a major challenge in the clinical practice. In the 1970s such patients were treated in association with emergency situations and essential surgery using huge amounts of FVIII/FIX concentrates often preceded by extracorporal adsorption of antibodies against FVIII/FIX. However, moderate to mild bleedings were not effectively treated. A certain hemostatic effect of activated prothrombin complex concentrates (aPCC) not exceeding 65% was reported. Unfortunately, also thromboembolic events occurred, which made them less attractive to use in inhibitor patients. In a dog model the thrombogenic effects on the coagulation system was almost completely avoided by adding antithrombin... (More)
- Hemophilia patients with inhibitors against FVIII/FIX present with a major challenge in the clinical practice. In the 1970s such patients were treated in association with emergency situations and essential surgery using huge amounts of FVIII/FIX concentrates often preceded by extracorporal adsorption of antibodies against FVIII/FIX. However, moderate to mild bleedings were not effectively treated. A certain hemostatic effect of activated prothrombin complex concentrates (aPCC) not exceeding 65% was reported. Unfortunately, also thromboembolic events occurred, which made them less attractive to use in inhibitor patients. In a dog model the thrombogenic effects on the coagulation system was almost completely avoided by adding antithrombin and heparin, suggesting factors like IXa, Xa or XIa to be responsible. On the other hand FVIIa is not readily inactivated by antithrombin in the circulation. Furthermore, a detailed literature review revealed very high levels of FVII in the aPCC used with some success in the treatment of hemophilia patients with inhibitors. The potential possibility to use FVIIa as a hemostatic agent was investigated by the administration of pure human FVIIa to two hemophilia patients with inhibitors. In both, a hemostatic effect was recorded. The development of recombinant FVIIa was initiated by Novo Nordisk A/S, Denmark, in June 1986 resulting in NovoSeven (rFVIIa) being licensed for use in patients with inhibitors against coagulation factors in EU in 1996. By then, a hemostatic effect of rFVIIa also in non-hemophilia patients such as patients with platelet dysfunctions or suffering from profuse, heavy bleedings initiated by extensive surgery or trauma had been demonstrated. In parallel the mechanism of action of pharmacological doses of rFVIIa was investigated resulting in a revision of the hemostatic process in stressing the compartmentalization of the process to TF-bearing cells and to thrombin activated platelets at the site of injury. The initial thrombin generation is generated by the formation of the TF-FVIIa-complex formed initially on the TF-bearing cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1582786
- author
- Hedner, Ulla LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Thrombosis Research
- volume
- 125 Suppl 1
- pages
- 4 - 6
- publisher
- Elsevier
- external identifiers
-
- wos:000275787800002
- pmid:20188400
- scopus:77949273934
- pmid:20188400
- ISSN
- 1879-2472
- DOI
- 10.1016/j.thromres.2010.01.021
- 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
- 1088b420-3f46-4ffb-a133-55bb41d5a691 (old id 1582786)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20188400?dopt=Abstract
- date added to LUP
- 2016-04-04 07:17:24
- date last changed
- 2022-01-29 02:00:25
@article{1088b420-3f46-4ffb-a133-55bb41d5a691,
abstract = {{Hemophilia patients with inhibitors against FVIII/FIX present with a major challenge in the clinical practice. In the 1970s such patients were treated in association with emergency situations and essential surgery using huge amounts of FVIII/FIX concentrates often preceded by extracorporal adsorption of antibodies against FVIII/FIX. However, moderate to mild bleedings were not effectively treated. A certain hemostatic effect of activated prothrombin complex concentrates (aPCC) not exceeding 65% was reported. Unfortunately, also thromboembolic events occurred, which made them less attractive to use in inhibitor patients. In a dog model the thrombogenic effects on the coagulation system was almost completely avoided by adding antithrombin and heparin, suggesting factors like IXa, Xa or XIa to be responsible. On the other hand FVIIa is not readily inactivated by antithrombin in the circulation. Furthermore, a detailed literature review revealed very high levels of FVII in the aPCC used with some success in the treatment of hemophilia patients with inhibitors. The potential possibility to use FVIIa as a hemostatic agent was investigated by the administration of pure human FVIIa to two hemophilia patients with inhibitors. In both, a hemostatic effect was recorded. The development of recombinant FVIIa was initiated by Novo Nordisk A/S, Denmark, in June 1986 resulting in NovoSeven (rFVIIa) being licensed for use in patients with inhibitors against coagulation factors in EU in 1996. By then, a hemostatic effect of rFVIIa also in non-hemophilia patients such as patients with platelet dysfunctions or suffering from profuse, heavy bleedings initiated by extensive surgery or trauma had been demonstrated. In parallel the mechanism of action of pharmacological doses of rFVIIa was investigated resulting in a revision of the hemostatic process in stressing the compartmentalization of the process to TF-bearing cells and to thrombin activated platelets at the site of injury. The initial thrombin generation is generated by the formation of the TF-FVIIa-complex formed initially on the TF-bearing cells.}},
author = {{Hedner, Ulla}},
issn = {{1879-2472}},
language = {{eng}},
pages = {{4--6}},
publisher = {{Elsevier}},
series = {{Thrombosis Research}},
title = {{History of rFVIIa therapy.}},
url = {{http://dx.doi.org/10.1016/j.thromres.2010.01.021}},
doi = {{10.1016/j.thromres.2010.01.021}},
volume = {{125 Suppl 1}},
year = {{2010}},
}