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The role of recombinant factor VIIa(FVIIa) in fibrin structure in the absence of FVIII/FIX

He, S; Blomback, M; Ekman, GJ and Hedner, Ulla LU (2003) In Journal of Thrombosis and Haemostasis 1(6). p.1215-1219
Abstract
Patients with hemophilia have an impaired thrombin Generation and therefore form loose fibrin hemostatic plugs that are easily dissolved by fibrinolysis. This prevents maintained hemostasis in these patients, resulting in a severe bleeding disorder. Recombinant (F)VIIa has been shown to enhance thrombin generation on already thrombin-activated platelets in the absence of FVIII and FIX. An efficacy rate of 80-90% has been found in hemophilia patients with inhibitors against FVIII or FIX both in association with major surgery and in the treatment of serious bleedings. In a model measuring fibrin clot permeability in a platelet-containing system described by Blomback et at. (1994) this was demonstrated to be dependent on the concentration of... (More)
Patients with hemophilia have an impaired thrombin Generation and therefore form loose fibrin hemostatic plugs that are easily dissolved by fibrinolysis. This prevents maintained hemostasis in these patients, resulting in a severe bleeding disorder. Recombinant (F)VIIa has been shown to enhance thrombin generation on already thrombin-activated platelets in the absence of FVIII and FIX. An efficacy rate of 80-90% has been found in hemophilia patients with inhibitors against FVIII or FIX both in association with major surgery and in the treatment of serious bleedings. In a model measuring fibrin clot permeability in a platelet-containing system described by Blomback et at. (1994) this was demonstrated to be dependent on the concentration of FVIII and FIX. The addition of rFVIIa in concentrations of 1.9. 4.8 and 9.6 mug mL (-1) normalized fibrin clot permeability. The concentration of 1.9 mug mL (-1) of rFVIIa normalized clot permeability in this system and the higher concentrations of rFVIIa added only slightly to the effect. No further decrease in clot permeability was found when rFVIIa in a concentration of 1.9 mug mL (-1) was added to a sample with a normal concentration (100%) of FVIII or FIX. Higher concentrations of rFVIIa added to the plasma containing 100% of FVIII or FIX induced only a slight further decrease of fibrin permeability constant, arguing against any unwanted effect of extra rFVIIa on clot permeability in the case of a normal hemostasis. Furthermore, the fibrin network was studied with 3D microscopy and the loose network found in the absence of FVIII or FIX increased in density with increasing FVIII or FIX concentrations. The addition of rFVIIa to FVIII- or FIX-deficient systems altered the network structure, making the fibers thinner and more tightly packed. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FVII, FIX, fibrin permeability, fibrin structure, FVIII, hemophilia, NovoSeven
in
Journal of Thrombosis and Haemostasis
volume
1
issue
6
pages
1215 - 1219
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:12871322
  • wos:000183823500018
  • scopus:0042989036
ISSN
1538-7933
DOI
10.1046/j.1538-7836.2003.00242.x
language
English
LU publication?
yes
id
20869773-fbe4-4010-bed3-f8d6103fe4db (old id 308066)
date added to LUP
2007-09-13 07:36:03
date last changed
2018-10-21 03:36:08
@article{20869773-fbe4-4010-bed3-f8d6103fe4db,
  abstract     = {Patients with hemophilia have an impaired thrombin Generation and therefore form loose fibrin hemostatic plugs that are easily dissolved by fibrinolysis. This prevents maintained hemostasis in these patients, resulting in a severe bleeding disorder. Recombinant (F)VIIa has been shown to enhance thrombin generation on already thrombin-activated platelets in the absence of FVIII and FIX. An efficacy rate of 80-90% has been found in hemophilia patients with inhibitors against FVIII or FIX both in association with major surgery and in the treatment of serious bleedings. In a model measuring fibrin clot permeability in a platelet-containing system described by Blomback et at. (1994) this was demonstrated to be dependent on the concentration of FVIII and FIX. The addition of rFVIIa in concentrations of 1.9. 4.8 and 9.6 mug mL (-1) normalized fibrin clot permeability. The concentration of 1.9 mug mL (-1) of rFVIIa normalized clot permeability in this system and the higher concentrations of rFVIIa added only slightly to the effect. No further decrease in clot permeability was found when rFVIIa in a concentration of 1.9 mug mL (-1) was added to a sample with a normal concentration (100%) of FVIII or FIX. Higher concentrations of rFVIIa added to the plasma containing 100% of FVIII or FIX induced only a slight further decrease of fibrin permeability constant, arguing against any unwanted effect of extra rFVIIa on clot permeability in the case of a normal hemostasis. Furthermore, the fibrin network was studied with 3D microscopy and the loose network found in the absence of FVIII or FIX increased in density with increasing FVIII or FIX concentrations. The addition of rFVIIa to FVIII- or FIX-deficient systems altered the network structure, making the fibers thinner and more tightly packed.},
  author       = {He, S and Blomback, M and Ekman, GJ and Hedner, Ulla},
  issn         = {1538-7933},
  keyword      = {FVII,FIX,fibrin permeability,fibrin structure,FVIII,hemophilia,NovoSeven},
  language     = {eng},
  number       = {6},
  pages        = {1215--1219},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {The role of recombinant factor VIIa(FVIIa) in fibrin structure in the absence of FVIII/FIX},
  url          = {http://dx.doi.org/10.1046/j.1538-7836.2003.00242.x},
  volume       = {1},
  year         = {2003},
}