|
|
Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-04-1199.
Submitted April 16, 2003
Accepted July 13, 2003
Co-inheritance of FV Leiden enhances thrombin formation and is associated with a mild bleeding phenotype in patients homozygous for the FVII 9726+5G A (FVII Lazio) mutation
Elisabetta Castoldi*, Jose W P Govers-Riemslag, Mirko Pinotti, Debora Bindini, Guido Tans, Mauro Berrettini, Maria Gabriella Mazzucconi, Francesco Bernardi, and Jan Rosing
Department of Biochemistry, Maastricht University, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy
Haemophilia Centre, University of Perugia, Perugia, Italy
Department of Cell Biotechnology and Haematology, La Sapienza University, Rome, Italy
* Corresponding author; email: e.castoldi{at}bioch.unimaas.nl.
We investigated the role of thrombophilic mutations as possible modifiers of the clinical phenotype in severe factor VII (FVII) deficiency. Among seven patients homozygous for a CRM- FVII defect (9726+5G A, FVII Lazio), the only virtually asymptomatic individual carried FV Leiden. Differential modulation of FVII levels by intragenic polymorphisms was excluded by a FVII-FX gene haplotype analysis. The coagulation efficiency in the FV Leiden carrier and a non-carrier was evaluated by measuring FXa, FVa and thrombin generation after extrinsic activation of plasma in the absence and presence of activated protein C (APC). In both patients coagulation factor activation was much slower and resulted in significantly lower amounts of FXa and thrombin than in a normal control. However, more FXa and thrombin were formed in the plasma of the patient carrying FV Leiden than in the non-carrier, especially in the presence of APC. These results were confirmed in FV-FVII-doubly deficient plasma reconstituted with purified normal FV or FV Leiden. The difference in thrombin generation between plasmas reconstituted with normal FV or FV Leiden gradually decreased at increasing FVII concentration. We conclude that co-inheritance of FV Leiden increases thrombin formation and can improve the clinical phenotype in patients with severe FVII deficiency.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Duckers, P. Simioni, L. Spiezia, C. Radu, S. Gavasso, J. Rosing, and E. Castoldi
Low plasma levels of tissue factor pathway inhibitor in patients with congenital factor V deficiency
Blood,
November 1, 2008;
112(9):
3615 - 3623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Herrmann, K. Wulff, R. Strey, A. Siegemund, J. Astermark, S. Schulman, and for the International Greifswald Registry of FVII
Variability of clinical manifestation of factor VII-deficiency in homozygous and heterozygous subjects of the European F7 gene mutation A294V
Haematologica,
August 1, 2008;
93(8):
1273 - 1275.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pinotti, L. Rizzotto, D. Balestra, M. A. Lewandowska, N. Cavallari, G. Marchetti, F. Bernardi, and F. Pagani
U1-snRNA-mediated rescue of mRNA processing in severe factor VII deficiency
Blood,
March 1, 2008;
111(5):
2681 - 2684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Castoldi, J. M. Brugge, G. A. F. Nicolaes, D. Girelli, G. Tans, and J. Rosing
Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations
Blood,
June 1, 2004;
103(11):
4173 - 4179.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
