A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism.
BACKGROUND
The factor V Leiden mutation is a common genetic defect associated with an increased risk for venous thromboembolism. The clinical implications for asymptomatic carriers of this mutation and, consequently, the usefulness of screening families in which a proband has both the mutation and venous thromboembolism are unclear.


OBJECTIVE
To determine the incidence of venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation.


METHODS
Prospective cohort study.


METHODS
University hospitals in the Netherlands.


METHODS
470 asymptomatic carriers of the factor V Leiden mutation (234 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were homozygous. Carriers were identified by screening the first-degree relatives (>15 years of age) of 247 symptomatic probands.


METHODS
Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations.


RESULTS
Nine venous thromboembolic events were observed in 1564 observation-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy.


CONCLUSIONS
The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation is low and does not justify routine screening of the families of symptomatic patients.
Middeldorp
S
S
Department of Vascular Medicine, Academic Medical Center F4-277, 1100 DE Amsterdam, the Netherlands.
Meinardi
J R
JR
Koopman
M M
MM
van Pampus
E C
EC
Hamulyák
K
K
van Der Meer
J
J
Prins
M H
MH
Büller
H R
HR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D017354:Point Mutation; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology* / Q000235:genetics; D020246:Venous Thrombosis / Q000453:epidemiology* / Q000235:genetics
C095381:factor V Leiden; D005165:Factor V