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The effect of platelets on fibrin gel structure formed in the presence of recombinant factor VIIa in hemophilia plasma and in plasma from a patient with Glanzmann thrombasthenia

He, S; Ekman, G J and Hedner, Ulla LU (2005) In Journal of Thrombosis and Haemostasis 3(2). p.272-279
Abstract
Fibrin gel structure has been shown to be dependent on the thrombin concentration as well as the rate of thrombin generation. Accordingly, factor VIII (FVIII)and FIX-deficient plasma (hemophilia A and B) form loose fibrin clots with high permeability constants. By adding rFVIIa in vitro to FVIII-deficient plasma containing platelets (frozen and thawed), the fibrin gel permeability constant normalized, indicating that extra rFVIIa (1.2 mug mL(-1) or higher) induced a tight fibrin structure. Thrombin generation is highly dependent on the number of platelets, and in this study it was demonstrated that the addition of rFVIIa (5 mug mL(-1)) normalizes the fibrin gel permeability in samples containing platelets (frozen-thawed) in numbers of at... (More)
Fibrin gel structure has been shown to be dependent on the thrombin concentration as well as the rate of thrombin generation. Accordingly, factor VIII (FVIII)and FIX-deficient plasma (hemophilia A and B) form loose fibrin clots with high permeability constants. By adding rFVIIa in vitro to FVIII-deficient plasma containing platelets (frozen and thawed), the fibrin gel permeability constant normalized, indicating that extra rFVIIa (1.2 mug mL(-1) or higher) induced a tight fibrin structure. Thrombin generation is highly dependent on the number of platelets, and in this study it was demonstrated that the addition of rFVIIa (5 mug mL(-1)) normalizes the fibrin gel permeability in samples containing platelets (frozen-thawed) in numbers of at least down to 20 x 106 mL(-1). The effect of rFVIIa was not observed when unfrozen platelets instead of frozen-thawed platelets were added. Neither was any effect on the fibrin permeability seen, in the presence of annexin V, known to block the effect of phospholipids on the platelet surface. This indicates an important role of platelet phospholipids for the effect of rFVIIa. A similar effect on the fibrin permeability of rFVIIa was observed when added to platelet-rich plasma from a patient with Glanzinarm thrombasthenia. Recombinant FVIIa has been found to induce hemostasis in patients with hemophilia and inhibitors against FVIII/FIX as well as in patients with Glanzmann thrombasthenia, indicating the importance of the formation of a tight fibrin gel structure, more resistant against premature proteolysis, for maintaining hemostasis. In conclusion, the addition of rFVIIa (5 mug mL(-1)) also substantially decreased the permeability constant of fibrin gels formed in FVIII-deficient plasma in the presence of low numbers of frozen-thawed platelets (down to 20 x 10(6) mL(-1)). A similar pattern was obtained in plasma from a Glanzmann patient. No effect was found in the presence of unfrozen instead of frozen-thawed platelets. Annexin V blocked any effect of rFVIIa. A normalization of the overall fibrinolysis potential (OFP) during the same condition supports the effect of rFVIIa on the fibrin permeability in the presence of a limited number of platelets. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
potential (OFP), overall fibrinolysis, fibrin permeability, activated FVII, FVII, thrombin generation
in
Journal of Thrombosis and Haemostasis
volume
3
issue
2
pages
272 - 279
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:15670032
  • wos:000226918000016
  • scopus:20844443318
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2005.01127.x
language
English
LU publication?
yes
id
5af0b821-45af-4ed5-b4a5-5adbd922db4a (old id 254268)
date added to LUP
2007-09-28 08:37:35
date last changed
2017-11-05 03:41:12
@article{5af0b821-45af-4ed5-b4a5-5adbd922db4a,
  abstract     = {Fibrin gel structure has been shown to be dependent on the thrombin concentration as well as the rate of thrombin generation. Accordingly, factor VIII (FVIII)and FIX-deficient plasma (hemophilia A and B) form loose fibrin clots with high permeability constants. By adding rFVIIa in vitro to FVIII-deficient plasma containing platelets (frozen and thawed), the fibrin gel permeability constant normalized, indicating that extra rFVIIa (1.2 mug mL(-1) or higher) induced a tight fibrin structure. Thrombin generation is highly dependent on the number of platelets, and in this study it was demonstrated that the addition of rFVIIa (5 mug mL(-1)) normalizes the fibrin gel permeability in samples containing platelets (frozen-thawed) in numbers of at least down to 20 x 106 mL(-1). The effect of rFVIIa was not observed when unfrozen platelets instead of frozen-thawed platelets were added. Neither was any effect on the fibrin permeability seen, in the presence of annexin V, known to block the effect of phospholipids on the platelet surface. This indicates an important role of platelet phospholipids for the effect of rFVIIa. A similar effect on the fibrin permeability of rFVIIa was observed when added to platelet-rich plasma from a patient with Glanzinarm thrombasthenia. Recombinant FVIIa has been found to induce hemostasis in patients with hemophilia and inhibitors against FVIII/FIX as well as in patients with Glanzmann thrombasthenia, indicating the importance of the formation of a tight fibrin gel structure, more resistant against premature proteolysis, for maintaining hemostasis. In conclusion, the addition of rFVIIa (5 mug mL(-1)) also substantially decreased the permeability constant of fibrin gels formed in FVIII-deficient plasma in the presence of low numbers of frozen-thawed platelets (down to 20 x 10(6) mL(-1)). A similar pattern was obtained in plasma from a Glanzmann patient. No effect was found in the presence of unfrozen instead of frozen-thawed platelets. Annexin V blocked any effect of rFVIIa. A normalization of the overall fibrinolysis potential (OFP) during the same condition supports the effect of rFVIIa on the fibrin permeability in the presence of a limited number of platelets.},
  author       = {He, S and Ekman, G J and Hedner, Ulla},
  issn         = {1538-7933},
  keyword      = {potential (OFP),overall fibrinolysis,fibrin permeability,activated FVII,FVII,thrombin generation},
  language     = {eng},
  number       = {2},
  pages        = {272--279},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {The effect of platelets on fibrin gel structure formed in the presence of recombinant factor VIIa in hemophilia plasma and in plasma from a patient with Glanzmann thrombasthenia},
  url          = {http://dx.doi.org/10.1111/j.1538-7836.2005.01127.x},
  volume       = {3},
  year         = {2005},
}