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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3678-3682
High levels of factor IX increase the risk of venous thrombosis
Astrid van Hylckama Vlieg,
Irma K. van der Linden,
Rogier M. Bertina, and
Frits R. Rosendaal
From the Department of Clinical Epidemiology and Hemostasis and
Thrombosis Research Center, Leiden University Medical Center,
Leiden, The Netherlands.
Elevated plasma levels of factor VIII (> 150 IU/dL) are an
important risk factor for deep vein thrombosis (DVT). Factor VIII is
the cofactor of factor IXa in the activation of factor X. The risk of
thrombosis in individuals with an elevated factor IX level is unknown.
This study investigated the role of elevated factor IX levels in the
development of DVT. We compared 426 patients with a first objectively
diagnosed episode of DVT with 473 population controls. This study was
part of a large population-based case-control study on risk factors for
venous thrombosis, the Leiden Thrombophilia Study (LETS).
Using the 90th percentile measured in control subjects (P90 = 129 U/dL) as a cutoff point for factor IX
levels, we found a 2- to 3-fold increased risk for individuals who have
factor IX levels above 129 U/dL compared with individuals having factor IX levels below this cutoff point. This risk was not affected by
adjustment for possible confounders (age, sex, oral contraceptive use,
and high levels of factor VIII, XI, and vitamin K-dependent proteins).
After exclusion of individuals with known genetic disorders, we
still found an odds ratio (OR) of 2.5 (95% confidence interval [CI]:
1.6-3.9). The risk was higher in women (OR: 2.6, CI: 1.6-4.3) than in
men (OR: 1.9, CI: 1.0-3.6) and appeared highest in the group of
premenopausal women not using oral contraceptives (OR: 12.4, CI:
3.3-47.2). These results show that an elevated level of factor IX is a
common risk factor for DVT.
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