PB1459 - A decreased endogenous thrombin potential is associated with recurrent venous thromboembolism

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Geke C. Poolen, MSc

PhD student
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands

Co-Author(s)

Romy De Laat-Kremers, PhD

Post-doctoral Research Project Leader
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
VS

Veronica Schmalschlager

Research Technician
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands Synapse Research Institute, Maastricht, The Netherlands.
Maastricht, Limburg, Netherlands
HM

Harmen Middelveld

Research Technician
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands Synapse Research Institute, Maastricht, The Netherlands.
Maastricht, Limburg, Netherlands
Geert-Jan Geersing, MD, PhD

Associate Professor
Department General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Utrecht, Utrecht, Netherlands
Rolf T. Urbanus, PhD

Associate professor
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Utrecht, Utrecht, Netherlands
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Roger E.G Schutgens, MD, PhD, MSc (he/him/his)

Internist-hematologist, Professor
Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht and University Utrecht, Utrecht, The Netherlands
Utrecht, Utrecht, Netherlands

Background: Recurrence of venous thromboembolism (VTE) is difficult to predict with clinical parameters only. Thrombin generation (TG) parameters might be useful in the prediction of recurrent VTE. However, the association between recurrence and TG is unclear and sometimes contradictory. Thrombin dynamics (TD) can be used to further unravel TG data by discriminating prothrombin conversion and thrombin inactivation.

Aims: To investigate the association of TG and TD parameters with VTE recurrence.

Methods: We used stored samples from the Vista trial, a randomized controlled trial evaluating treatment duration of VTE based on the Vienna Prediction Model. 869 patients with unprovoked VTE were recruited at nine local thrombosis services in the Netherlands. Two years of follow-up was obtained and primary outcome was recurrence. Plasma samples were collected during (T=0; N=600) and one month after stopping anticoagulation (T=28; N=514). TG was measured by calibrated automated thrombinography and TD parameters were calculated. Associations between parameters and recurrence were analyzed with logistic regression after correction for age, sex, d-dimer, index event and hormone use.

Results: 11% of patients had recurrent VTE (Table 1). None of the TG parameters were associated with recurrence when measured during anticoagulation (T=0). In a multivariate analysis, a 100-point increase of ETP at T=28 was associated with a reduced risk of recurrence measured with PPP reagent low (OR 0.91, 95%CI 0.84-0.99) and PPP reagent (OR 0.89, 95%CI 0.81-0.99) (Table 2). Other TG parameters (at T=28) were not associated with recurrence. TD parameters of prothrombin conversion and thrombin inactivation were not associated with recurrent VTE either. Furthermore, D-dimer levels were associated with increased recurrence risk (OR 1.04 per 100ug/ml increase, 95%CI 1.02-1.07).

Conclusion(s): We observed increased D-dimer levels and a decreased ETP in our patient population with recurrent VTE. This could indicate an increased turn-over of coagulation factors in patients with an increased risk of recurrent VTE.