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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. 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. 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 (r s = 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). 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. • TPO-RAs lead to a significant increase in platelet microparticle levels. • TPO-RA treatment does not induce enhanced platelet aggregation responses. • TPO-RA-treated ITP patients yield impaired aggregation responses to ADP and collagen. • TPO-RAs may exert selective effects on ristocetin-induced aggregation. [ABSTRACT FROM AUTHOR]