Thromb Haemost 2008; 99(01): 223-228
DOI: 10.1160/TH07-08-0515
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Thrombin generation in first-degree relatives of patients with venous thromboembolism who have factor V Leiden

A pilot study
Francis Couturaud
1   G.E.T.B.O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), EA 3878, Department of Internal Medicine and Chest Diseases
,
Jèrôme Duchemin
2   Haematology Unit, University Hospital of Brest, Brest, Francew
,
Christophe Leroyer
1   G.E.T.B.O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), EA 3878, Department of Internal Medicine and Chest Diseases
,
Bènèdicte Delahousse
3   Haematology Unit, University Hospital of Tours, Tours, France
,
Jean François Abgrall
2   Haematology Unit, University Hospital of Brest, Brest, Francew
,
Dominique Mottier
1   G.E.T.B.O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), EA 3878, Department of Internal Medicine and Chest Diseases
,
for the Groupe d’Etude de la Thrombose de Bretagne Occidentale (G.E.T.B.O) › Author Affiliations
Further Information

Publication History

Received: 22 August 2007

Accepted after major revision: 15 November 2007

Publication Date:
24 November 2017 (online)

Summary

The thrombin generation test appears to be a highly sensitive and specific test in the detection of thrombophilia in patients with venous thromboembolism. We aimed to determine the accuracy of the thrombin generation test to detect factorV Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden. Sixty-two first-degree relatives of 21 index cases were tested for factor V Leiden, the G20210A prothrombin gene mutation and thrombin generation. Information about oestrogen therapy and previousVTE was also collected. The normalized Thrombomodulin sensitivity ratio (n-TMsr) was defined as the ratio of endogenous thrombin potential determined in the presence and absence of thrombomodulin which was normalized against the same ratio determined in normal control plasma. The mean n-TMsr was 1.37 (± 0.33) in the 45 relatives with one or more prothrombotic state (factor V Leiden, G20210A prothrombin mutation, oestrogen therapy or hormonal therapy) and 1.02 (± 0.34) in the 17 relatives without prothrombotic state (p = 0.001). The positive predictive value was 90.3 (95%CI, 73.1 – 97.4). In relatives with an abnormal n-TMsr, the adjusted odds ratio for having a prothrombotic state was 8.3 (95%CI, 1.9 – 36.9) and the adjusted odds ratio for having the factor V Leiden was 14.3 (95%CI, 2.9 – 71.2).An abnormal thrombin generation test appears highly predictive for having factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden.

 
  • References

  • 1 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293: 2351-2361.
  • 2 Ho WK, Hankey GJ, Quinlan DJ. et al. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med 2006; 166: 729-736.
  • 3 Middeldorp S, Henkens CMA, Koopman MMW. et al. The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med 1998; 128: 15-20.
  • 4 Simioni P, Sanson BJ, Prandoni P. et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost 1999; 81: 198-202.
  • 5 Couturaud F, Kearon C, Leroyer C. et al. for the Groupe d’Etude de la Thrombose de Bretagne Occidentale (G.E.T.B.O) Incidence of venous thromboembolism in first-degree relatives of patients with venous thromboembolism who have factor V Leiden. Thromb Haemost 2006; 96: 744-749.
  • 6 Kearon C, Gent M, Hirsh J. et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340: 901-907.
  • 7 Ridker PM, Goldhaber SZ, Danielson E. et al. PREVENT investigators. Long term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425-1434.
  • 8 Baglin T. The measurement and application of thrombin generation. Brit J Haematol 2005; 130: 653-661.
  • 9 Hemker HC, Giesen P, Al Dieri R. et al. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb 2002; 32: 249-253.
  • 10 De Visser MCH, Van Hylckama Vlieg A, Tans G. et al. Determinants of the APTT- and ETP-based APC sensitivity tests. J Thromb Haemost 2005; 3: 1488-1494.
  • 11 Curvers J, Thomassen MMC, Rimmer J. et al. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistancce test. Thromb Haemost 2002; 88: 5-11.
  • 12 Dargaud Y, Trzeciak C, Bordet JC. et al. Use of calibrated automated thrombinography ± thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost 2006; 96: 562-567.
  • 13 Hron G, Kollars M, Binder BR. et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296: 397-402.
  • 14 Hull RD, Hirsh J, Carter CJ. et al. Pulmonary angiography, ventilation lung scanning and venography for clinically suspected pulmonary embolism with abnormal pulmonary perfusion lung scan. Ann Intern Med 1983; 98: 891-899.
  • 15 Kearon C, Julian J, Newman TE. et al. Non invasive diagnosis of deep venous thrombosis. Ann Intern Med 1998; 128: 663-677.
  • 16 The PIOPED investigators.. Value of the ventilation perfusion lung scan in acute pulmonary embolism. JAMA 1990; 263: 2753.
  • 17 Leroyer C, Mercier B, Escoffe M. et al. Factor V Leiden prevalence in venous thromboembolism patients. Chest 1997; 111: 1603-1606.
  • 18 Bevers EM, Janssen MP, Willems GM. et al. No evidence for enhanced thrombin formation through displacement of annexin V by antiphospholipid antibodies. Thromb Haemost 2000; 83: 792-794.
  • 19 Mayer LD, Hope MJ, Cullis PR. Vesicles of variables sizes produced by a rapid extrusion procedure. Biochem Biophys Acta 1986; 858: 161-168.
  • 20 Duchemin J, Pittet JL, Tartary M. et al. A new assay based on TG inhibition to detect both protein C and protein S deficiencies in plasma. Thromb Haemost 1994; 71: 331-338.