ABSTRACT
Essentials Thrombopoietin (TPO) lowers the threshold for platelet activation. TPO receptor agonists (RAs) may therefore also lead to platelet activation. Patients with chronic liver disease and thrombocytopenia participated in a randomized trial. The TPO-RA avatrombopag did not increase platelet activation in vivo or reactivity in vitro. BACKGROUND: The thrombopoietin (TPO) receptor agonist (TPO-RA) avatrombopag has recently been Food and Drug Administration-approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure. The TPO receptor c-mpl is expressed on the platelet surface, and TPO lowers the threshold for platelet activation. TPO-RAs may therefore also lead to platelet activation. OBJECTIVES: To evaluate the effects of avatrombopag on platelet activation. PATIENTS/METHODS: CLD patients with thrombocytopenia participated in a randomized, double-blind, placebo-controlled, parallel-group study. No patient received a platelet transfusion within 10 days of study blood draws. Platelet activation was evaluated with whole blood flow cytometry (which, unlike other methods, is accurate in thrombocytopenic samples). RESULTS: Avatrombopag, but not placebo, increased platelet counts. As measured by platelet surface P-selectin and activated glycoprotein IIb-IIIa: (i) the numbers of circulating activated platelets were not increased in avatrombopag-treated patients as compared with placebo-treated patients; and (ii) platelet reactivity to low and high concentrations of ADP and thrombin receptor-activating peptide was not increased in avatrombopag-treated patients as compared with placebo-treated patients. CONCLUSIONS: In this randomized, double-blind, placebo-controlled, parallel-group study of CLD patients with thrombocytopenia, avatrombopag increased platelet counts but did not increase platelet activation in vivo or platelet reactivity in vitro.
