High levels of factor IX increase the risk of venous thrombosis

• Published in: Blood Vol. 95; no. 12; pp. 3678 - 3682
• Main Authors: Vlieg, Astrid van Hylckama, van der Linden, Irma K., Bertina, Rogier M., Rosendaal, Frits R.
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.06.2000
• Subjects: Adult; Age Factors; Aged; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Contraceptives, Oral; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Enzyme-Linked Immunosorbent Assay; Factor IX - analysis; Female; Humans; Male; Medical sciences; Middle Aged; Netherlands - epidemiology; Postmenopause; Premenopause; Reference Values; Risk Factors; Venous Thrombosis - blood; Venous Thrombosis - epidemiology; Netherlands; Europe; Vascular disease; Human; Factor IX; Risk factor; Cardiovascular disease; Case control study; Vein; Epidemiology; Coagulation factor; Thrombosis; Public health; Venous disease
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V95.12.3678

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.