title: Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism.
abstract: Tissue factor pathway inhibitor (TFPI) regulates factor X activation. Low TFPI is a risk factor for a first venous thrombosis. We evaluated whether low TFPI confers an increased risk of recurrent venous thromboembolism (VTE). TFPI-free antigen was measured in 611 patients with a first spontaneous VTE, and who were prospectively followed after withdrawal of anticoagulation. The endpoint was symptomatic recurrent VTE. The relative risk (RR) of recurrence increased from 1.0 (95% CI 0.4-2.6) in patients with TFPI levels < or = 5th percentile to 2.7 (95% CI 1.0-7.4) in patients with levels < or = 2nd percentile as compared with higher levels. At five years, the probability of recurrence was 48.6% (95th CI 19.0-78.1) among patients with TFPI < or = 2nd percentile and 16.8% (95th CI 13.8-19.8) among those with higher levels (p=0.04). Compared to patients with wild type factor V and high TFPI, the RR of recurrence was 1.1 (95% CI 0.7-1.7) in patients with factor V Leiden and high TFPI, 2.3 (95% CI 0.6-9.5) in patients with wild type factor V and low TFPI and 3.5 (95% CI 0.9-14.3) in patients with factor V Leiden and low TFPI. In a multivariate analysis,the high risk of recurrence in carriers of factor V Leiden and low TFPI slightly decreased [RR 2.8 (95% CI 0.6-9.5)]. We conclude that thrombosis patients with low levels of free TFPI are at an increased risk of recurrent VTE.
authors.affiliation: Department of Internal Medicine I, Div of Hematology/Hemostasis, Medical University of Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoke
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kyrle
authors.forename: Erich
authors.initials: E
authors.lastname: Minar
authors.forename: Christine
authors.initials: C
authors.lastname: Bialonzcyk
authors.forename: Mirko
authors.initials: M
authors.lastname: Hirschl
authors.forename: Barbara
authors.initials: B
authors.lastname: Schneider
authors.forename: Marietta
authors.initials: M
authors.lastname: Kollars
authors.forename: Ansgar
authors.initials: A
authors.lastname: Weltermann
authors.forename: Sabine
authors.initials: S
authors.lastname: Eichinger
mesh_terms: D015331:Cohort Studies; D005165:Factor V / Q000378:metabolism; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000097:blood* / Q000453:epidemiology*; D012008:Recurrence; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood* / Q000453:epidemiology*
chemical_list: D008074:Lipoproteins; C095381:factor V Leiden; C051928:lipoprotein-associated coagulation inhibitor; D005165:Factor V