Prediction of recurrent venous thromboembolism by measuring ProC Global

Sabine Eichinger; Gregor Hron; Mirko Hirschl; Christine Bialonczyk; Erich Minar; Marietta Kollars; Paul A. Kyrle

doi:10.1160/TH07-05-0376

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(06): 1232-1236
DOI: 10.1160/TH07-05-0376

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Prediction of recurrent venous thromboembolism by measuring ProC Global

Sabine Eichinger

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

,

Gregor Hron

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

,

Mirko Hirschl

²Department of Angiology, Hanuschkrankenhaus, Vienna, Austria

,

Christine Bialonczyk

³Department of Dermatology, Wilhelminenspital, Vienna, Austria

,

Erich Minar

⁴Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Marietta Kollars

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

,

Paul A. Kyrle

¹Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

› Author Affiliations

Abstract

Summary

In patients with venous thromboembolism (VTE) a laboratory assay that globally measures the overall thrombophilic tendency is not available. We hypothesized that determination of ProC^® Global, a plasma assay which tests the global function of the protein C pathway, could be used to stratify patients according to their risk of recurrent VTE. We prospectively followed 774 patients with first spontaneous VTE for a mean time of 52 months. ProC Global normalized ratio (NR) was measured in plasma by use of a commercially available assay based on activated partial thromboplastin time. Ninety-eight of the 774 patients had recurrent VTE. Patients with ProC Global NR ≥ 0.75 had a relative risk of recurrence of 0.59 (95% CI 0.40–0.87) as compared with those with lower ratio. After four years, cumulative probability of recurrence was 8.6% in patients with ProC Global NR ≥ 0.75 and 17.4% in patients with a lower ratio (p=0.006). Patients with a high ProC Global NR have a low risk of recurrent VTE. ProC Global NR can be used to stratify patients with a first unprovoked VTE according to their risk of recurrence.

Keywords

Venous thrombosis - recurrence - ProC Global

Full Text

References

References
1 Mannucci PM. Laboratory detection of inherited thrombophilia: a historical perspective. Semin Thromb Hemost 2005; 31: 5-10.
2 Palareti G, Legnani C, Cosmi B. et al. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87: 7-12.
3 Eichinger S, Minar E, Bialonczyk C. et al. D-dimer levels and risk of recurrent venous thromboembolism. J Am Med Assoc 2003; 290: 1071-1074.
4 Tripodi A, Chantarangkul V, Martinelli I. et al. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004; 104: 3631-3634.
5 Hron G, Eichinger S, Weltermann A. et al. Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time. J Thromb Haemost 2006; 4: 750-751.
6 Brummel-Ziedins KE, Vossen CY, Butenas S. et al. Thrombin generation profiles in deep venous thrombosis. J Thromb Haemost 2005; 3: 2497-2505.
7 Hron G, Kollars M, Binder BR. et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. J Am Med Assoc 2006; 296: 397-402.
8 Eichinger S, Hron G, Weltermann A. et al. Endogenous thrombin potential (ETP) for assessing the risk of recurrent venous thromboembolism. Blood 2005; 106: 1622A.
9 Dati F, Hafner G, Erbes H. et al. ProC Global: the first functional screening assay for the complete protein C pathway. Clin Chem 1997; 43: 1719-1723.
10 Grand’Maison A, Bates SM, Johnston M. et al. “ProC Global”; a functional screening test that predicts recurrent venous thromboembolism. Thromb Haemost 2005; 93: 600-604.
11 Kyrle PA, Minar E, Bialonczyk C. et al. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350: 2558-2563.
12 Brandt JT, Triplett DA, Alving B. et al. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995; 74: 1185-1190.
13 Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: NY: John Wiley & Sons; 1980
14 Kaplan EL, Meier P. Nonparametreic estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-481.
15 Schulman S, Ogren M. New concepts in optimal management of anticoagulant therapy for extended treatment of venous thromboembolism. Thromb Haemost 2006; 96: 258-266.
16 Mannucci PM. The measurement of multifactorial thrombophilia. Thromb Haemost 2002; 88: 1-2.
17 Kraus M, Noah M, Fickenscher K. The PCAT – a simple screening assay for assessing the functionality of the protein C anticoagulant pathway. Thromb Res 1995; 79: 217-222.
18 Toulon P, Halbmeyer WM, Hafner G. et al. Screening for abnormalities in the protein C anticoagulant pathway using the ProC Global assay. Results of a European multicenter evaluation. Blood Coag Fibrinol 2000; 11: 447-454.
19 Sarig G, Aberbach I, Schliamser L. et al. Evaluation of ProC Global assay in women with a history of venous thromboembolism on hormonal therapy. Thromb Haemost 2006; 96: 578-583.
20 Buller HR, Agnelli G, Hull RD. et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 401S-428S.