Abstract
BACKGROUND: There is clinical need for a laboratory biomarker to identify patients who, following an unprovoked venous thrombosis (VTE), are at low VTE recurrence risk and can discontinue anticoagulation after a limited treatment duration (3-6 m). This secondary analysis of the ExACT study aimed to evaluate whether quantitation of peripheral blood endothelial progenitor cells (EPCs) could improve prediction of VTE recurrence risk. METHODS: The ExACT study was a non-blinded, multicentre RCT comparing extended vs discontinued anticoagulation following a first unprovoked VTE. Adult patients were eligible if they had completed ≥3 months anticoagulation and remained anticoagulated. The primary outcome was time to first recurrent VTE from randomisation. Blood samples were taken at baseline and results correlated with clinical outcome over 2 years follow up. (Trial registration: ISRCTN:73819751 and EUDRACT:2101-022119-20). FINDINGS: 281 patients were recruited, randomised (between July 2011 and February 2015) and followed up for 24 months (Male:Female 2:1, mean age 63). Of these, 273 patients were included in the final analysis. Blood samples were received at baseline for Full Blood Count(n = 216), d-dimers(n = 205) and endothelial progenitor cell (EPC) quantitation by flow cytometry(n = 193). VTE recurrence was lower in the extended vs discontinued anticoagulation arms (5% vs 23%, HR 0.20(95%CI:0.09-0.46,p < 0.001)). Level of EPCs were lower in patients who later developed VTE recurrence (43.41 ± 7.69 cells/ml vs 87.1 ± 7.15 cells/ml, p = 0.02). Survival free from VTE recurrence was significantly improved in patients with EPCs ≥ 100 cells/ml vs EPCs < 100 cells/ml (HR 0.10(95%CI:0.01-0.75,p = 0.025)). INTERPRETATION: If confirmed, EPC quantitation may represent a novel biomarker that identifies patients at low VTE recurrence risk who are suitable for limited duration anticoagulation.