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Thromb Haemost 2010; 104(02): 207-212
DOI: 10.1160/TH09-10-0693
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Total tissue factor pathway inhibitor and venous thrombosis

The Longitudinal Investigation of Thromboembolism Etiology
Neil A. Zakai
1   Departments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
,
Pamela L. Lutsey
2   School of Public Health, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota, USA
,
Aaron R. Folsom
2   School of Public Health, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota, USA
,
Susan R. Heckbert
3   Department of Epidemiology, University of Washington, Seattle, Washington, USA
,
Mary Cushman
1   Departments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
› Author Affiliations
Financial support: ARIC is supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC 55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, with additional support from R01-HL-59367, all from the National Heart, Lung, and Blood Institute, Bethesda, MD. CHS is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129 and N01-HC-15103 and research project grant R01HL054711 from the National Heart, Lung, and Blood Institute, Bethesda, MD. LITE is supported by a grant from the National Heart, Lung, and Blood Institute (R01 HL59367).
Further Information

Publication History

Received: 10 October 2009

Accepted after major revision: 03 March 2010

Publication Date:
24 November 2017 (online)

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Summary

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor, a potent coagulation initiator. Limited evidence suggests that low TFPI levels are associated with increased risk of venous thromboembolism (VTE). We measured total TFPI in a nested case-control study in the Longitudinal Investigation of Thromboembolism Etiology. Control subjects were frequency matched 2:1 to cases on age, sex, race, and cohort. Odds ratios (ORs) for VTE by TFPI levels were computed using logistic regression models adjusting for age, race, sex, coagulation factors (factors VII, VIII, IX, XI, D-dimer), and body mass index (BMI). To evaluate for greater than additive interactions, we calculated the percent relative excess risk due to interaction between TFPI and other VTE risk factors. A total of 534 cases of VTE occurred and matched to 1,091 controls. Mean baseline TFPI in ng/ml (standard deviation) in those who developed VTE and controls was 36.4 (12.8) and 35.0 (11.1), respectively. Higher TFPI was associated with male sex, age, BMI, factors VII, VIII, IX, XI, and D-dimer. TFPI level did not differ by ethnicity, factor V Leiden, or pro-thrombin G20210A. Compared with those in the upper 95%, the bottom 5% of TFPI had an age-, sex-, race-, and study-adjusted OR (95% CI) of 1.35 (0.86, 2.12) for VTE. Adjusting for factors VII, VIII, IX, and XI the OR was 1.93 (1.05, 3.53). Further addition of D-dimer and BMI to this model decreased the OR to 1.70 (0.98, 2.93). Low TFPI did not demonstrate greater than additive interaction with other VTE risk factors.

Keywords

Venous thrombosis - tissue factor pathway inhibitor - epidemiologic studies
 

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