OC 23.3 - Recurrent venous-thromboembolism: association with thrombin generation and D-Dimer

Background: In patients with a first event of venous thrombo-embolism (VT) clinicians must decide when to stop anticoagulation, evaluating the risk of recurrent thrombosis.

Aims: The aim of this study was to evaluate the association between recurrent VT and D-Dimer and thrombin generation.

Methods: Analyses were performed in 1895 patients enrolled in the MEGA study (539 with unprovoked first VT) and followed up for recurrent VT (252 events). All patients gave informed consent and the study was approved by the Medical Ethics Committee of the Leiden University Medical Center.
Thrombin generation was measured with low and high tissue factor concentration. Results obtained with high tissue factor (normalized ratio with and without activated protein C) are shown.
The cumulative incidence of recurrent VT and incidence rates with 95% CI of recurrent VT were calculated. Hazard ratios and 95% CI were calculated by Cox proportional hazard regression models, to evaluate relative risks of VT associated with different levels of D-Dimer and thrombin generation.
For the combined analysis of D-Dimer and thrombin generation, we chose the cut-off of 215 ng/mL for D-Dimer and the highest decile for thrombin generation.

Results: In patients with a first unprovoked VT, three levels of risk of recurrent VT were identified in the combined analysis: incidence rates per 100 patient-years in low risk in patients with low D-Dimer and low thrombin generation (1.36, 95% CI 0.42-2.30); intermediate risk in patients with high D-Dimer (3.89, 95% CI 3.07-4.70) and high risk in patients with high D-Dimer and thrombin generation (9.80, 95% CI 5.28-14.33).

Conclusion(s): The use of both tests allowed to identify patients with a high risk of recurrent VT, who could benefit from long-term anticoagulation, in the absence of a severe bleeding risk.