High Thrombin Generation Measured In the Presence of Activated Protein C Is Associated with An Increased Risk of Recurrence Among Women 18–64 Years After a First Event of VTE

Patients with venous thrombosis (VTE) have a high risk of a recurrence after discontinuation of anticoagulants. Both prolonged anticoagulant treatment with increased risk for bleeding and a recurrence reduces quality of life. In women younger than 65 years old the recurrence rate is relatively low. However, identification of the patients at risk of a recurrence remains difficult.

The aim of our study was to investigate whether a global coagulation test such as thrombin generation can be used as a marker for the increased risk of a recurrence of VTE among women of 18–65 years old after a first event of deep venous thrombosis (DVT) or pulmonary embolism (PE).

139 women with an objectively documented first event of DVT or PE were enrolled into the study at diagnosis. Plasma was collected at least 4 weeks after discontinuation of anticoagulant treatment. Patients with cancer or pregnancy within 3 months after the first event were excluded. All patients were followed up prospectively for median 47 months. Recurrences of VTE were objectively documented. No participants were taking oral estrogens treatment during the follow up. Thrombin generation was measured via calibrated automated thrombography (CAT), in the absence and in the presence of activated protein C (APC). The APC sensitivity ratio (APCsr) was calculated to estimate APC-resistance. All participants were screened for factor V Leiden and G20210A mutation.

The ETP and peak height in the presence of APC (ETP_+APC, peak height_+APC) were associated with a recurrence of VTE in a log-rank test. In a multivariate cox-regression patients with the ETP_+APC > 169 nM*min had hazard ratios (HR) for recurrent VTE of 8.8 (p=0,008) compared to patients with the ETP_+APC < 169 nM*min. Patients with the peak height_+APC > 58 nM had HR of 7.2 (p=0,014). Patients with the APCsr > 3.32 had HR of 6,7 (p=0,006) for recurrence of VTE. Age, inherited thrombophilia (factor V Leiden, G20210A mutation) and BMI> 30 were included into the multivariate analysis. Conclusion: High thrombin generation in the presence of APC in women after a first event of VTE is indicative for an increased risk of a recurrence. Our data suggest that acquired APC resistance is a risk factor for recurrent VTE.

No relevant conflicts of interest to declare.