Thrombin generation and activated protein C resistance in the absence of factor V Leiden correlates with the risk of recurrent venous thromboembolism in women aged 18–65 years

Abstract

Identification of patients at high risk of recurrence after a first event of venous thromboembolism (VTE) remains difficult. Resistance to activated protein C (APC) is a known risk factor for VTE, but data on the risk of recurrence is controversial. We wanted to investigate whether APC resistance in the absence of factor V Leiden, determined with global coagulation test such as the thrombin generation assay, could be used as a marker for increased risk of recurrent VTE among women 18-65 years old after a first event of VTE. In a cohort of 243 women with a first event of VTE, plasma was collected after discontinuation of anticoagulant treatment and the patients were followed up for 46 months (median). Thrombin generation was measured via calibrated automated thrombography, at 1 pM and 10 pM of tissue factor (TF). In women without factor V Leiden (n=117), samples were analysed in the absence and in the presence of APC. Increase in ETP (endogenous thrombin potential) and peak height analysed in the presence of APC correlated significantly with higher risk of recurrence. At 1 pM, peak height correlated with increased risk of recurrence. In 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. We also found that thrombin generation at low TF (1 pM) is correlated with the risk of recurrence. Our data suggest that APC resistance in the absence of factor V Leiden is a risk factor for recurrent VTE.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study

“…The association of inflammation biomarkers with diagnosis, severity, and poor prognosis of cerebrovascular events has already been reported, especially in patients with CVST [ 15 , [20] , [21] , [22] , [23] , [24] , [25] ]. Recently, a multicenter prospective observational study was conducted in Portugal: the Pathophysiology of Venous Infarction – Prediction of Infarction and Recanalization in CVT (PRIORITy-CVT) study, including 62 patients, demonstrated that biomarkers associated with inflammation predicted poor prognosis in cerebral vein thrombosis (CVT) [ 15 ]. In this study, patients had more unfavorable outcomes than the FPCCVT cohort (21% vs 3% of deaths, respectively).…”

“…No study has yet evaluated the association of D-dimer with CVST clinical manifestations. Besides, thrombin generation (TG) has been proposed as a global assay to evidence hypocoagulable [ 10 , 11 ] and hypercoagulable states [ [12] , [13] , [14] ]: increased TG is an independent predictor of recurrent venous thrombosis [ 15 ]. Inflammation biomarkers, such as fibrinogen and high-sensitivity C-reactive protein (hs-CRP), have been recently described as possible predictors of poor prognosis in CVST [ 16 ].…”