Thromb Haemost 2005; 94(04): 787-790
DOI: 10.1160/TH05-06-0412
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism

Matthias Hoke
1   Department of Internal Medicine I, Div. of Hematology/Hemostasis, Medical University of Vienna, Vienna, Austria
,
Paul A. Kyrle
1   Department of Internal Medicine I, Div. of Hematology/Hemostasis, Medical University of Vienna, Vienna, Austria
,
Erich Minar
2   Department of Internal Medicine II, Div. of Angiology, Medical University of Vienna, Vienna, Austria
,
Christine Bialonzcyk
3   Wilhelminenspital, Department of Dermatology, Vienna, Austria
,
Mirko Hirschl
4   Hanuschkrankenhaus, Department of Angiology, Vienna, Austria
,
Barbara Schneider
5   Institute of Medical Statistics, Medical University of Vienna, Vienna, Austria
,
Marietta Kollars
1   Department of Internal Medicine I, Div. of Hematology/Hemostasis, Medical University of Vienna, Vienna, Austria
,
Ansgar Weltermann
1   Department of Internal Medicine I, Div. of Hematology/Hemostasis, Medical University of Vienna, Vienna, Austria
,
Sabine Eichinger
1   Department of Internal Medicine I, Div. of Hematology/Hemostasis, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received13 June 2005

Accepted after revision23 July 2005

Publication Date:
07 December 2017 (online)

Summary

Tissue factor pathway inhibitor (TFPI) regulates factor X activation. LowTFPI 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 spontaneousVTE, 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 ≤ 5th percentile to 2.7 (95% CI 1.0–7.4) in patients with levels ≤ 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 ≤ 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 factorV 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 freeTFPI are at an increased risk of recurrent VTE.

 
  • References

  • 1 Broze Jr GJ, Miletich JP. Characterization of the inhibition of tissue factor in serum. Blood 1987; 69: 150-5.
  • 2 Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP. Structure and biology of tissue factor pathway inhibitor. Thromb Haemost 2001; 86: 959-72.
  • 3 Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze Jr. G J. Plasma antigen levels of the lipoproteinassociated coagulation inhibitor in patients samples. Blood 1991; 78: 387-93.
  • 4 Sakata T, Mannami T, Baba S, Kokubo Y. et al. Potential of free-form TFPI and PAI-1 to be useful markers of early atherosclerosis in a Japanese general population (the Suita Study): association with the intimal-medial thickness of carotid arteries. Atherosclerosis 2004; 176: 355-60.
  • 5 Abumiya T, Yamaguchi T, Terasaki T. et al. Decreased plasma tissue factor pathway inhibitor activity in ischemic stroke patients. Thromb Haemost 1995; 74: 1050-4.
  • 6 Blann AD, Amiral J, McCollum CN. et al. Differences in free and total tissue factor pathway inhibitor, and tissue factor in peripheral artery disease compared to healthy controls. Atherosclerosis 2000; 152: 29-34.
  • 7 Creasey AA, Chang AC, Feigen L. et al. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91: 2850-60.
  • 8 Abraham E, Reinhart K, Opal S. et al. OPTIMIST Trial Study Group. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003; 290: 238-47.
  • 9 Ariens RA, Alberio G, Moia M. et al. Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis. Thromb Haemost 1999; 81: 203-7.
  • 10 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: 4387-92.
  • 11 Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001; 344: 1222-31.
  • 12 Eichinger S, Weltermann A, Minar E. et al. Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism. Arch Intern Med 2004; 164: 92-6.
  • 13 van't Veer C, Kalafatis M, Bertina R M. et al. Increased tissue factor-initiated prothrombin activation as a result of the Arg506 –> Gln mutation in factor V Leiden. J Biol Chem 1997; 272: 20721-9.
  • 14 Eitzman DT, Westrick RJ, Bi X. et al. Lethal perinatal thrombosis in mice resulting from the interaction of tissue factor pathway inhibitor deficiency and factor V Leiden. Circulation 2002; 105: 2139-42.
  • 15 The PIOPED. Investigators. Value of the ventilation/ perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990; 263: 2753-69.
  • 16 Bertina RM, Koeleman BP, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
  • 17 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
  • 18 Weltermann A, Eichinger S, Bialonczyk C. et al. The risk of recurrent venous thromboembolism among patients with high factor IX levels. J Thromb Haemost 2003; 1: 28-32.
  • 19 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-62.
  • 20 Kalbfleisch JD, Prentice RL. >The statistical analysis of failure time data.. New York: John Wiley; 1980
  • 21 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81.
  • 22 Van Dreden P, Grosley M, Cost H. Total and free levels of tissue factor pathway inhibitor: a risk factor in patients with factor V Leiden? Blood Coagul Fibrinolysis. 1999; 10: 115-6.