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FVIII/VWF complex displays a greater pro-haemostatic activity than FVIII preparations devoid of VWF: Study in plasma and cell-based models.
- Source :
-
Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2020 Jul; Vol. 26 (4), pp. e151-e160. Date of Electronic Publication: 2020 Apr 23. - Publication Year :
- 2020
-
Abstract
- Introduction: Plasma-derived FVIII/VWF complex was reported to be less sensitive to inhibitors than FVIII preparations devoid of VWF.<br />Aim: To compare the efficacy of FVIII/VWF complex (Fanhdi) and five different VWF-free FVIII preparations in restoring thrombin generation and activation of thrombin-activatable fibrinolysis inhibitor (TAFI) in haemophilic plasma, with and without inhibitor, and in cell-based models.<br />Methods: Experiments were performed in haemophilic plasma supplemented with inhibitory IgG or in plasma samples obtained from haemophilia A patients without (n = 11) and with inhibitor (n = 12). Thrombin generation was evaluated by calibrated automated thrombography (CAT) under standard conditions, in the presence of activated protein C (APC) or thrombomodulin (TM), and in cell-based models including endothelial cells, either alone or in combination with platelets or tissue factor-expressing blood mononuclear cells. The kinetics of TAFI activation was determined by a two-stage functional assay in the absence and in the presence of APC.<br />Results: In haemophilic plasma without inhibitor, Fanhdi enhanced thrombin generation and TAFI activation as well as recombinant (2nd-4th generation) and plasma-derived FVIII preparations devoid of VWF. On the contrary, in plasma with inhibitor, Fanhdi displayed a greater ability to restore thrombin generation and TAFI activation under all tested conditions. Notably, in cell-based models including endothelial cells, Fanhdi proved more efficient than all other preparations in improving thrombin generation even in the absence of inhibitor.<br />Conclusion: The greater pro-haemostatic activity of FVIII/VWF complex, either in haemophilic plasma with inhibitor or in the presence of endothelial cells, may offer therapeutic advantages.<br /> (© 2020 John Wiley & Sons Ltd.)
- Subjects :
- Carboxypeptidase B2 drug effects
Carboxypeptidase B2 metabolism
Carboxypeptidase B2 pharmacology
Coagulants pharmacology
Coagulants therapeutic use
Combined Modality Therapy
Endothelial Cells drug effects
Endothelial Cells metabolism
Factor VIII therapeutic use
Fibrinolysis drug effects
Hemophilia A blood
Hemostasis drug effects
Hemostasis physiology
Humans
Immunoglobulin G metabolism
Kinetics
Plasma metabolism
Protein C metabolism
Thrombin drug effects
Thrombin metabolism
Thrombomodulin metabolism
Thromboplastin metabolism
Treatment Outcome
von Willebrand Factor therapeutic use
Factor VIII pharmacology
Hemophilia A drug therapy
von Willebrand Factor pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2516
- Volume :
- 26
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Haemophilia : the official journal of the World Federation of Hemophilia
- Publication Type :
- Academic Journal
- Accession number :
- 32325538
- Full Text :
- https://doi.org/10.1111/hae.14008