Platelet Apoptosis and PAI-1 are Involved in the Pro-Coagulant State of Immune Thrombocytopaenia Patients Treated with Thrombopoietin Receptor Agonists.
Thromb Haemost
; 119(4): 645-659, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30743272
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Coagulantes
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Púrpura Trombocitopênica Idiopática
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Inibidor 1 de Ativador de Plasminogênio
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Apoptose
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Receptores de Trombopoetina
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article