Total tissue factor pathway inhibitor and venous thrombosis

Neil A. Zakai; Pamela L. Lutsey; Aaron R. Folsom; Susan R. Heckbert; Mary Cushman

doi:10.1160/TH09-10-0693

Thrombosis and Haemostasis, Table of Contents

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

¹Departments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA

,

Pamela L. Lutsey

²School of Public Health, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota, USA

,

Aaron R. Folsom

²School of Public Health, Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota, USA

,

Susan R. Heckbert

³Department of Epidemiology, University of Washington, Seattle, Washington, USA

,

Mary Cushman

¹Departments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA

› Author Affiliations

Abstract

PDF Download

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

PDF (185 kb)

References

References
1 Lindahl AK. Tissue factor pathway inhibitor: a potent inhibitor of in-vitro coagulation and in-vivo thrombus formation. Curr Opin Lipidol 1994; 05: 434-439.
2 Holst J, Lindblad B, Bergqvist D. et al. Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1–161) in experimental venous thrombosis--a comparison with low molecular weight heparin. Thromb Haemost 1994; 71: 214-219.
3 Dahm A, Rosendaal FR, Andersen TO. et al. Tissue factor pathway inhibitor anti-coagulant activity: risk for venous thrombosis and effect of hormonal state. Br J Haematol 2006; 132: 333-338.
4 Hoke M, Kyrle PA, Minar E. et al. Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism. Thromb Haemost 2005; 94: 787-790.
5 Cushman M, Tsai AW, White RH. et al. Deep vein thrombosis and pulmonary em-bolism in two cohorts: the Longitudinal Investigation of Thromboembolism Etiology. Am J Med 2004; 117: 19-25.
6 The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives The ARIC investigators. Am J Epidemiol 1989; 129: 687-702.
7 Fried LP, Borhani NO, Enright P. et al. The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991; 01: 263-276.
8 Tsai AW, Cushman M, Rosamond WD. et al. Coagulation factors, inflammation markers, and venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).[see comment]. Am J Med 2002; 113: 636-642.
9 Chambless LE, McMahon R, Wu K. et al. Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study. Ann Epidemiol 1992; 02: 723-733.
10 Folsom AR, Wu KK, Rosamond WD. et al. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997; 96: 1102-1108.
11 Cushman M, Folsom AR, Wang L. et al. Fibrin fragment D-dimer and the risk of future venous thrombosis. [see comment]. Blood 2003; 101: 1243-1248.
12 Dahm A, Van Hylckama Vlieg A, Bendz B. et al. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood 2003; 101: 4387-4392.
13 Koster T, Rosendaal FR, Reitsma PH. et al. Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms--the Leiden Thrombophilia Study (LETS). Thromb Haemost 1994; 71: 719-722.
14 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Wille-brand factor on occurrence of deepvein thrombosis. Lancet 1995; 345: 152-155.
15 van Hylckama Vlieg A, van der Linden IK, Bertina RM. et al. High levels of factor IX increase the risk of venous thrombosis. Blood 2000; 95: 3678-3682.
16 Meijers JC, Tekelenburg WL, Bouma BN. et al. High levels of coagulation factor XI as a risk factor for venous thrombosis. New Engl J Med 2000; 342: 696-701.
17 Zakai NA, Ohira T, White R. et al. Activated partial thromboplastin time and risk of future venous thromboembolism. Am J Med 2008; 121: 231-238.
18 Knol MJ, van der Tweel I, Grobbee DE. et al. Estimating interaction on an additive scale between continuous determinants in a logistic regression model. Int J Epidemiol 2007; 36: 1111-1118.
19 Duering C, Kosch A, Langer C. et al. Total tissue factor pathway inhibitor is an independent risk factor for symptomatic paediatric venous thromboembolism and stroke. Thromb Haemost 2004; 92: 707-712.
20 Amini-Nekoo A, Futers TS, Moia M. et al. Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis. Br J Haematol 2001; 113: 537-543.
21 Andreescu AC, Cushman M, Rosendaal FR. D-dimer as a risk factor for deep vein thrombosis: the Leiden Thrombophilia Study. Thromb Haemost 2002; 87: 47-51.
22 Hoibraaten E, Qvigstad E, Andersen TO. et al. The effects of hormone replacement therapy (HRT) on hemostatic variables in women with previous venous thromboembolism--results from a randomized, double-blind, clinical trial. Thromb Haemost 2001; 85: 775-781.