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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2720-2725
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
A prospective study of venous thromboembolism in relation to
factor V Leiden and related factors
Aaron R. Folsom,
Mary Cushman,
Michael Y. Tsai,
Nena Aleksic,
Susan R. Heckbert,
Lori L. Boland,
Albert W. Tsai,
N. David Yanez, and
Wayne D. Rosamond
From the Division of Epidemiology, School of Public
Health, and Department of Laboratory Medicine and Pathology, University
of Minnesota, Minneapolis; Department of Medicine, University of
Vermont, Burlington; Division of Hematology, University of Texas
Medical School, Houston; Department of Epidemiology and Department of
Biostatistics, University of Washington, Seattle; and Collaborative
Studies Coordinating Center, University of North Carolina, Chapel Hill.
The aim of this study was to examine the occurrence of venous
thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in
335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95% CI,
2.20-6.12) in participants carrying factor V Leiden compared with
noncarriers. APC resistance measured after predilution with factor
V-deficient plasma conferred an OR of 2.58 (95% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of
VTE for homozygosity was estimated to be 5.5 (95% CI, 2.45-12.5).
Carriers of the HR2 haplotype otherwise were not at increased risk of
VTE overall (OR = 1.05; 95% CI, 0.64-1.72), but double heterozygotes
for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95% CI, 1.7-159) compared with noncarriers. Factor V antigen also was
not associated with VTE overall, but for participants with the
combination of high factor V antigen plus factor V Leiden the OR of
idiopathic VTE was 11.5 (95% CI, 4.2-31.4). In the general population,
APC resistance and factor V Leiden were important VTE risk factors;
homozygosity for the HR2 haplotype may be a risk factor but was rare;
otherwise, HR2 haplotype and factor V antigen were not risk factors
except in carriers of factor V Leiden.
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