title: Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia.
abstract: Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.
authors: Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. simon.panzer@meduniwien.ac.at
authors: Johanna
authors: J
authors: Haselboeck
authors: Alexandra
authors: A
authors: Kaider
authors: Ingrid
authors: I
authors: Pabinger
authors: Simon
authors: S
authors: Panzer
mesh_terms: D000244:Adenosine Diphosphate; D000328:Adult; D001317:Austria; D001565:Benzoates / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003094:Collagen; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D011720:Pyrazoles / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists* / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; D009842:Oligopeptides; D019007:P-Selectin; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C546937:SELP protein, human; C504808:Ser-Phe-Phe-Leu-Arg-Asn; D000244:Adenosine Diphosphate; D003094:Collagen; C520809:eltrombopag