title: Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis.
abstract: There is now strong experimental evidence that tissue factor pathway inhibitor (TFPI) is a critical inhibitor to modulate tissue factor-induced coagulation, but the role of TFPI as a risk factor for thrombosis is yet to be to be determined. This study investigated the role of low TFPI levels for the development of deep-vein thrombosis (DVT). We determined TFPI activity and TFPI-free and total antigen levels in the subjects enrolled in the Leiden Thrombophilia Study, which is a large population-based case-control study of 474 patients and 474 controls. The odds ratio (OR) for DVT in subjects who had TFPI-free antigen levels below the 10th percentile, as compared with those who had TFPI-free antigen levels above this cutoff, was 1.7 (95% confidence interval [CI], 1.1-2.6). The ORs for low TFPI activity and low total antigen were also mildly increased. When the 5th percentile was used as a cutoff, the ORs were 2.1 (95% CI, 1.1-4.1) for both TFPI-free antigen and TFPI total antigen. Exogenous female hormones had a profound lowering effect on TFPI levels, with lower levels in oral contraceptive users than in premenopausal nonusers, who had lower levels than men and postmenopausal women. These results indicate that low levels of TFPI, especially low TFPI-free and total antigen in plasma, constitute a risk factor for DVT.
authors.affiliation: Department of Hematology, Ullevål University Hospital, Oslo, Norway. a.e.a.dahm@klinmed.uio.no
authors.forename: Anders
authors.initials: A
authors.lastname: Dahm
authors.forename: Astrid
authors.initials: A
authors.lastname: Van Hylckama Vlieg
authors.forename: Bjorn
authors.initials: B
authors.lastname: Bendz
authors.forename: Frits
authors.initials: F
authors.lastname: Rosendaal
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Bertina
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects; D008297:Male; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology*
chemical_list: D003276:Contraceptives, Oral; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor