Impact of environmental and hereditary risk factors on the clinical manifestation of thrombophilia in homozygous carriers of factor V:G1691A.
BACKGROUND
Limited data exist on the clinical manifestations of homozygous factor (F)V:G1691A mutation (FV Leiden) and the impact of environmental and genetic risk factors.


OBJECTIVE
To assess the contribution of these factors on the thrombophilic phenotype.


METHODS
In a retrospective multicenter cohort study 165 individuals with homozygous FV:G1691A mutation, of whom 129 had previous venous thromboembolism (VTE), were included. To study the role of environmental risk factors, patients were compared by the use of a standardized questionnaire to 165 sex- and age-matched individuals (reference group A); of these, two had previous VTE. To assess the role of genetic risk factors, factor (F)II:G20210A and MTHFR:C677T were determined in individuals homozygous for FV:G1691A and in 177 healthy individuals without previous VTE (reference group B).


RESULTS
The first VTE occurred significantly earlier in women (median age 25 years) than men (35.5 years). In 81% of women and 29% of men an environmental risk factor was present before first VTE. Oral contraceptives increased the risk of thrombosis 4-fold [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.7, 10.4] in women with homozygous FV:G1691A. Postoperative and post-traumatic VTE as first manifestation occurred in 13% and 15% of surgical/traumatic events in patients and in 0.7% and 1.8% in reference group A, respectively (OR 19.7, 95% CI 2.5, 154 and OR 9.2, 95% CI 1.1, 79.4). Heterozygous FII:G20210A was more prevalent in symptomatic patients (11.7%) compared with reference group B (2.8%, OR 4.6, 95% CI 1.6, 13.2). The prevalence of homozygous MTHFR:C677T genotype was similar in patients and reference group B.


CONCLUSIONS
Our study supports the concept of thrombophilia as a multifactorial disorder. The knowledge of coexisting factors predisposing to VTE is useful for medical advice for primary and secondary prophylaxis in these patients.
Ehrenforth
S
S
Department of Internal Medicine I, University Hospital Frankfurt, Germany.
Nemes
L
L
Mannhalter
C
C
Rosendaal
F R
FR
Koder
S
S
Zoghlami-Rintelen
C
C
Scharrer
I
I
Pabinger
I
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004777:Environment; D005060:Europe; D005165:Factor V / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D012307:Risk Factors; D013923:Thromboembolism / Q000235:genetics*; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V