Thrombin Generation Is Associated with Venous Thromboembolism Recurrence, but Not with Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study

Author:

Vrotniakaite-Bajerciene Kristina12ORCID,Rütsche Sereina12,Calzavarini Sara12,Quarroz Claudia12,Stalder Odile3,Mean Marie45,Righini Marc6ORCID,Staub Daniel7ORCID,Beer Juerg H.8,Frauchiger Beat9,Osterwalder Joseph10,Kucher Nils11,Matter Christian M.1213ORCID,Husmann Marc14,Banyai Martin15,Aschwanden Markus7,Mazzolai Lucia16,Hugli Olivier17ORCID,Rodondi Nicolas418,Aujesky Drahomir4,Angelillo-Scherrer Anne12

Affiliation:

1. Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland

2. Department for BioMedical Research, University of Bern, 3010 Bern, Switzerland

3. Clinical Trials Unit (CTU) Bern, University of Bern, 3010 Bern, Switzerland

4. Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland

5. Department of Medicine, Lausanne University Hospital, Lausanne University, 1005 Lausanne, Switzerland

6. Division of Angiology and Hemostasis, Geneva University Hospital, 1205 Geneva, Switzerland

7. Division of Angiology, Basel University Hospital, 4031 Basel, Switzerland

8. Department of Internal Medicine, Cantonal Hospital of Baden, 5404 Baden, Switzerland

9. Department of Internal Medicine, Cantonal Hospital of Frauenfeld, 8501 Frauenfeld, Switzerland

10. Cantonal Hospital of St. Gallen, 9000 St. Gallen, Switzerland

11. Clinic of Angiology, University Hospital Zurich, 8091 Zurich, Switzerland

12. Department of Cardiology, University Heart Center, University Hospital Zurich, 8091 Zurich, Switzerland

13. Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital and University of Zurich, 8091 Zurich, Switzerland

14. Center for Vascular Diseases, Zurich-Stadelhofen, Stadelhoferstrasse 8, 8001 Zurich, Switzerland

15. Gefässpraxis Luzern Swiss AG, Pilatusstrasse 34, 6003 Lucerne, Switzerland

16. Service of Angiology, Lausanne University Hospital, Lausanne University, 1005 Lausanne, Switzerland

17. Emergency Department, Lausanne University Hospital, Lausanne University, 1005 Lausanne, Switzerland

18. Institute of Primary Health Care (BIHAM), University of Bern, 3010 Bern, Switzerland

Abstract

It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, or mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding, and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65 years with acute VTE were followed for 2 years, starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding, and mortality. Thrombin generation was assessed in 551 patients 1 year after the index VTE. At this time, 59% of the patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12–14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28–3.73) in the presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identify among elderly patients those at higher risk of VTE recurrence.

Funder

Swiss National Science Foundation

Publisher

MDPI AG

Subject

General Medicine

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