Platelet Apoptosis and PAI-1 are Involved in the Pro-Coagulant State of Immune Thrombocytopaenia Patients Treated with Thrombopoietin Receptor Agonists

Raul Justo Sanz; Elena Monzón Manzano; Ihosvany Fernández Bello; Maria Teresa Álvarez Román; Mónica Martín Salces; Maria Isabel Rivas Pollmar; Víctor Jiménez Yuste; Nora V. Butta

doi:10.1055/s-0039-1678706

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2019; 119(04): 645-659
DOI: 10.1055/s-0039-1678706

Cellular Haemostasis and Platelets

Georg Thieme Verlag KG Stuttgart · New York

Platelet Apoptosis and PAI-1 are Involved in the Pro-Coagulant State of Immune Thrombocytopaenia Patients Treated with Thrombopoietin Receptor Agonists

Raul Justo Sanz

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

,

Elena Monzón Manzano

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

,

Ihosvany Fernández Bello

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

,

Maria Teresa Álvarez Román

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

,

Mónica Martín Salces

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

,

Maria Isabel Rivas Pollmar

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

,

Víctor Jiménez Yuste

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

²Universidad Autónoma de Madrid, Madrid, Spain

,

Nora V. Butta

¹Hematology Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain

› Author Affiliations

Abstract

The treatment goal for patients with immune thrombocytopaenia (ITP) is to raise platelet counts to levels that minimize or stop bleeding. Thrombopoietin receptor agonists (TPO-RAs) have been successfully and extensively employed as second-line therapy for ITP. However, TPO-RAs have a small but significant increase in the risk of thrombosis. The aim of this study was to elucidate the mechanisms involved in the pro-coagulant effect of TPO-RAs to take them into account when considering their use in ITP patients with concomitant diseases/conditions that might increase risk of suffering thrombotic events. Eighty-two patients with chronic primary ITP (40 untreated and 42 undergoing TPO-RA therapy) and 112 healthy individuals were recruited. The patients with ITP undergoing TPO-RA therapy presented a pro-coagulant profile due to the formation of a more fibrinolysis-resistant clot because of increased plasminogen activator inhibitor-1 (PAI-1) levels. Increase in platelet content of PAI-1 might be the result of the effect of TPO-RA during megakaryopoiesis, as suggested by experiments performed in MEG-01 cells. Moreover, patients under TPO-RA treatment presented an enhanced pro-coagulant activity associated with microparticles and an increased platelet apoptosis that causes a higher exposure of phosphatidylserine and, consequently, a larger surface for the binding of the prothrombinase complex.

Keywords

immune thrombocytopaenia - platelet apoptosis - PAI-1 - thrombopoietin receptor agonists - platelet function

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References

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