The risk of a first and a recurrent venous thrombosis associated with an elevated D‐dimer level and an elevated thrombin potential: results of the THE‐VTE study

Background D‐dimer and thrombin generation have been associated with the risk of recurrent venous thrombosis. However, for both measurements, different assays are available, and in vitro thrombin generation may be affected by the problem of contact activation during blood sampling. Objectives To determine the association between hypercoagulability and first and recurrent thrombosis by the use of different D‐dimer and thrombin generation assays, to assess whether the addition of corn trypsin inhibitor (CTI) prior to blood sampling to inhibit contact activation improved the association between thrombin generation and thrombosis risk, and to calculate the DASH score with two different D‐dimer assays. Methods A case–control study (626 patients and 361 controls) with subsequent follow‐up of the cases was performed (2987 patient‐years after stopping of anticoagulant therapy). Blood was drawn 2–3 months after discontinuation of anticoagulation for the first event in citrate tubes with and without CTI. Results/Conclusions An elevated D‐dimer level and elevated thrombin generation were associated with an increased risk of a first event regardless of the assay used (odds ratios: 1.8–3.4). An elevated D‐dimer level but not elevated thrombin generation was associated with the risk of recurrence. Patients with elevated D‐dimer levels had a more than two‐fold increased recurrence rate (Vidas – hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4–3.8; HemosIL – HR 2.4, 95% CI 1.5–3.9; Thrombinoscope and Technoclone assay – HR 1.3). Elimination of contact factor activation did not improve the predictive value of thrombin generation. In patients with unprovoked first events, the DASH score had a similar predictive value for deep vein thrombosis and pulmonary embolism, both when calculated with Vidas D‐dimer and when calculated with HemosIL D‐dimer.