Factor V Leiden (Hereditary Thrombotic Predisposition)
Resistance to Activated Protein C (RAPC) is the most common cause of
venous thrombosis. It is mediated by heterozygosity or (more rarely)
homozygosity for mutant Factor V (Arg506Gln, AKA, R506Q) Leiden
mutation).
In the general population, 6% of healthy Caucasian men and women are
heterozygous for the mutant Factor V allele.
If women are given oral contraceptives or estrogen supplementation, and
if they are heterozygous for the mutant allele, their risk of thrombosis is
80 times that of the general population.
In order to prevent thrombosis in thrombosis-prone women, we think that
all women, prior to starting postmenopausal estrogen supplementation or
oral contraceptives, should have a determination of RAPC/Factor V
Leiden determinations.
The approximately 6% with the mutant factor V Leiden gene should not
be given exogenous estrogens, whereas the 94% without the mutant
gene should be at very low risk of thrombosis.
References:
1. Dahlback, B. (1995) Resistance to activated protein C, the Arg-506 to
Gln mutation in the Factor V gene, and venous thrombosis. Thromb. and
Haemos. 73:739-42.
2. Voorberg, J. Roelse, J. Koopman R, et al., (1994) Association of
idiopathic venous thromboembolism with single point-mutation at Arg-506
of Factor V. The Lancet 343: 1535
3. Lalouschek, W., Suess, E., Aull, S., et al., Clinical and laboratory data
in heterozygous Factor V Leiden mutation positive versus negative
patients with TIA and minor stroke. Stroke 26:19634.
4. Bertina, R.M., Koeleman, B.P.C., Koster, T. et al., (1994) Mutation in
blood coagulation Factor V associated with resistance to activated
protein C. Nature 369:64-7.
5. Glueck, C.J., McMahon, R.E. Bouquot, J.E., et al., (1997)
Heterozygosity for the Leiden mutation of the Factor V gene, a common
pathoetiology for osteonecrosis of the jaw, with thrombophilia augmented
by exogenous estrogens. J. Lab. Clin Med., 130(5):540-3.
6. Glueck, C.J., Brandt, G. Gruppo, R. (1997) Resistance to activated
protein C and Legg-Perthis Disease. Clinical Orthopedic and Related
Research, 338:139-152.
7. Glueck, C.J. H. Bell, L. Vadlamani, A. Gupta, R.N. Fontaine, P. Wang,
D. Stroop and R. Gruppo (1999) Heritable thrombophilia and
hypofibrinolysis. Possible causes of retinal vein occlusion. Arch.
Opthalmol. 117:43-9.
8. Glueck, C.J. M.J. Kupferminc, R.N. Fontaine, P. Wang, B.B. Weksler
and A. Eldor. (2001) Genetic hypofibrinolysis in complicated
pregnancies. Obstet. and Gynecol. 97:44-8.
For more information go to National Center for Biotechnology Information
(NCBI).
Most abstracts and many full length articles can be printed from this web site.
You may also visit www.fvleiden.org for further information.
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