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Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia

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Abstract

Haemostatic complication is common for patients with hematologic malignancies. Recent studies suggest that the procoagulant activity (PCA) of extracellular vesicles (EV) may play a major role in venous thromboembolism and disseminated intravascular coagulation (DIC) in acute leukaemia. To study the impact of EVs from leukaemic patients on thrombin generation and to assess EV-PCA as a potential biomarker for thrombotic complications in patients with acute leukaemia. Blood samples from a cohort of patients with newly diagnosed acute leukaemia were obtained before treatment (D-0), 3 and 7 days after treatment (D-3 and D-7). Extracellular vesicles were isolated and concentrated by ultracentrifugation. EV-PCA was assessed by thrombin generation assay, and EV-associated tissue factor activity was measured using a commercial bio-immunoassay (Zymuphen MP-TF®). Of the 53 patients, 6 had increased EV-PCA at D-0 and 4 had a thrombotic event. Patients without thrombotic events (n = 47) had no elevated EV-PCA. One patient had increased EVs with procoagulant activity at D-3 and developed a DIC at D-5. This patient had no increased EVs-related tissue factor activity from D-0 to D-7 (<2 pg/ml). Eight patients had increased EVs with tissue factor activity (>2 pg/ml), of these, four had a thrombosis and two had haemorrhages. Procoagulant activity of extracellular vesicles could have a predictive value in excluding the risk of thrombotic events. Our findings also suggest a possible association between thrombotic events and EV-PCA.

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Abbreviations

VTE:

Venous thromboembolism

DIC:

Disseminated intravascular coagulation

AML:

Acute myeloblastic leukaemia

ALL:

Acute lymphoblastic leukaemia

EVs:

Extracellular vesicles

TF:

Tissue factor

PL:

Procoagulant phospholipids

PCA:

Procoagulant activity

TGA:

Thrombin generation assay

BMI:

Body mass index

D-0:

Before treatment

D-3:

3 days after treatment

D-7:

7 days after treatment

NPP:

Normal pooled plasma

UC:

Ultracentrifugation

SD:

Standard deviation

CTL:

Healthy volunteers control

TFPI:

Tissue factor pathway inhibitor

NPV:

Negative predictive value

PPV:

Positive predictive value

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Acknowledgements

The work was supported by Grant No 7.4545.11 from F.R.S. - FNRS Télévie Belgium.

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Authors and Affiliations

  1. Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Haematology Laboratory, NARILIS, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium

    Damien Gheldof, Hélène Haguet, Anne Sonet, Bernard Chatelain & François Mullier

  2. Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), NARILIS, University of Namur, Namur, Belgium

    Jean-Michel Dogné, Céline Bouvy, Christian Chatelain & François Mullier

  3. Biobank, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium

    Carlos Graux & Fabienne George

  4. Université catholique de Louvain, CHU UCL Namur, Haematology Department, rue Dr Gaston Therasse, 1, 5530, Yvoir, Belgium

    Anne Sonet

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  1. Damien Gheldof
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  2. Hélène Haguet
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  3. Jean-Michel Dogné
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  7. Anne Sonet
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  8. Christian Chatelain
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  9. Bernard Chatelain
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  10. François Mullier
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Correspondence to Damien Gheldof.

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Gheldof, D., Haguet, H., Dogné, JM. et al. Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia. J Thromb Thrombolysis 43, 224–232 (2017). https://doi.org/10.1007/s11239-016-1471-z

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