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. 2024 Dec:244:109211.
doi: 10.1016/j.thromres.2024.109211. Epub 2024 Nov 8.

A study of platelet function in patients with chronic immune thrombocytopenia treated with thrombopoietin receptor agonists

Christos Stafylidis  1 , Sevastianos Chatzidavid  2 , Panagiotis Diamantopoulos  2 , Dimitra Vlachopoulou  2 , Stavroula Syriopoulou  2 , Panagiota Katsiampoura  2 , Nefeli Giannakopoulou  2 , Abraham Pouliakis  3 , Ioanna Anastasopoulou  4 , Olga Katsarou  4 , Marina Mantzourani  2 , Nora-Athina Viniou  2
Affiliations

A study of platelet function in patients with chronic immune thrombocytopenia treated with thrombopoietin receptor agonists

Christos Stafylidis et al. Thromb Res. 2024 Dec.

Abstract

Background: Thrombopoietin receptor agonists (TPO-RAs) are widely used in immune thrombocytopenia (ITP) and are associated with increased thrombotic risk. However, data regarding their impact on platelet function is scarce.

Methods: Platelet function was evaluated in chronic ITP patients enrolled over one year, using light transmission aggregometry and platelet-derived microparticle (PMP) levels measurement with flow cytometry. Aggregation responses to various concentrations of ADP, collagen, ristocetin, and PMP levels were compared between TPO-RA-treated patients, patients treated with other agents and healthy individuals.

Results: TPO-RA-treated patients (n = 24) displayed significantly reduced aggregation responses to 2.5 μM, 5 μM, and 10 μM of ADP and collagen compared to 15 healthy individuals (59.5 % vs. 87.6 %, p < .0001, 43.6 % vs. 79.9 %, p < .0001, 26.1 % vs. 75.2 %, p < .0001, 67.2 % vs. 86 %, p < .0001, respectively). Reduced responses to ADP and collagen were also recorded in patients treated with other agents (n = 16) compared to healthy controls but without difference between the two treatment groups. Aggregation response to ristocetin was normal in all three groups. None of the patients yielded enhanced platelet aggregation. In TPO-RA-treated patients, a strong positive correlation between platelet counts and aggregation response to ristocetin was observed (rs = 0.65, p = .0005). PMP levels were significantly elevated in TPO-RA-treated patients compared to patients treated with other agents (49.5 vs 4.5 events/uL, p < .0001) and healthy controls (5 events/uL, p < .0001).

Conclusions: These results suggest that TPO-RAs may not enhance platelet aggregation responses, whereas impaired responses may be a disease feature. Furthermore, TPO-RAs may increase PMP levels and thus be implicated in the modulation of platelet function in ITP patients.

Keywords: Immune thrombocytopenia; Microparticles; Platelet aggregation; Platelet function; Thrombopoietin receptor agonists.

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Conflict of interest statement

Declaration of competing interest Nora-Athina Viniou reports a relationship with Novartis that includes: consulting or advisory. Nora-Athina Viniou reports a relationship with Astellas Pharma Inc. that includes: consulting or advisory. Nora-Athina Viniou reports a relationship with Janssen-Cilag that includes: consulting or advisory. Nora-Athina Viniou reports a relationship with Roche that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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