Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial.

Charlotte Bradbury; Tracey Buckley; Yong Zhong Sun; Peter Rose; David Fitzmaurice

doi:10.1016/j.eclinm.2019.11.011

Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial.

Charlotte Bradbury, Tracey Buckley, Yong Zhong Sun, Peter Rose, David Fitzmaurice

School of Cellular and Molecular Medicine

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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 (3-6m). 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.
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.

Original language	English
Article number	100218
Number of pages	9
Journal	EClinicalMedicine
Volume	17
DOIs	https://doi.org/10.1016/j.eclinm.2019.11.011
Publication status	Published - 27 Nov 2019

Keywords

anticoagulation
D-dimers
endothelial progenitor cells
recurrence
venous thrombosis
VTE

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Dr Charlotte A Bradbury
- c.bradburybristol.acuk
- Bristol Medical School (THS) - Consultant Senior Lecturer
Person: Academic

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Bradbury, C., Buckley, T., Sun, Y. Z., Rose, P., & Fitzmaurice, D. (2019). Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial. EClinicalMedicine, 17, Article 100218. https://doi.org/10.1016/j.eclinm.2019.11.011

@article{03eff100cb0e48a88bd5707ee73e72bb,

title = "Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial.",

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 (3-6m). 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.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. ",

keywords = "anticoagulation, D-dimers, endothelial progenitor cells, recurrence, venous thrombosis, VTE",

author = "Charlotte Bradbury and Tracey Buckley and Sun, {Yong Zhong} and Peter Rose and David Fitzmaurice",

year = "2019",

month = nov,

day = "27",

doi = "10.1016/j.eclinm.2019.11.011",

language = "English",

volume = "17",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Lancet Publishing Group",

}

Bradbury, C, Buckley, T, Sun, YZ, Rose, P & Fitzmaurice, D 2019, 'Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial.', EClinicalMedicine, vol. 17, 100218. https://doi.org/10.1016/j.eclinm.2019.11.011

Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial. / Bradbury, Charlotte; Buckley, Tracey; Sun, Yong Zhong et al.
In: EClinicalMedicine, Vol. 17, 100218, 27.11.2019.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE

T2 - Results from the ExACT Randomised Controlled Trial.

AU - Bradbury, Charlotte

AU - Buckley, Tracey

AU - Sun, Yong Zhong

AU - Rose, Peter

AU - Fitzmaurice, David

PY - 2019/11/27

Y1 - 2019/11/27

N2 - 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 (3-6m). 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.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.

AB - 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 (3-6m). 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.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.

KW - anticoagulation

KW - D-dimers

KW - endothelial progenitor cells

KW - recurrence

KW - venous thrombosis

KW - VTE

U2 - 10.1016/j.eclinm.2019.11.011

DO - 10.1016/j.eclinm.2019.11.011

M3 - Article (Academic Journal)

C2 - 31891148

SN - 2589-5370

VL - 17

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 100218

ER -

Bradbury C, Buckley T, Sun YZ, Rose P, Fitzmaurice D. Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial. EClinicalMedicine. 2019 Nov 27;17:100218. doi: 10.1016/j.eclinm.2019.11.011

Patients with High levels of Circulating Endothelial Progenitor Cells (EPC) following at least three months of anticoagulation for unprovoked Venous Thromboembolism (VTE) are at low risk of recurrent VTE: Results from the ExACT Randomised Controlled Trial.

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