title: Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura.
abstract: Eltrombopag, a thrombopoietin receptor agonist, has been approved for the treatment of patients with immune thrombocytopenia because of its abilities to enhance platelet production and reduce hemorrhage. Both platelet count and platelet adhesion are crucial to stop bleeding. Although eltrombopag is known to improve platelet counts, its effects on platelet adhesion are not yet known. This study aimed to assess the efficacy of eltrombopag on platelet production and platelet adhesive affinity. To evaluate the efficacy of low-dose eltrombopag (25 mg) for patients with chronic refractory immune thrombocytopenic purpura (ITP) and to determine the ex vivo platelet adhesion ability before and after treatment with eltrombopag, we conducted an open-label, multicenter study in which 25 Taiwanese patients with chronic ITP were enrolled. During the 6-month evaluation, the starting and maximum doses of eltrombopag were 25 and 50 mg, respectively, to maintain the platelet count of ≥50,000 per μL. Flow-based adhesion assay was used to detect the percentage of platelets adhering to immobilized von Willebrand factor-collagen on microslides. Of the enrolled patients, 48% achieved a platelet count of ≥50,000 per μL. Interestingly, 83% of all responders required 25 mg of eltrombopag daily to achieve the target platelet count. In addition, the percentage of bleeding patients was significantly reduced in both responders and nonresponders by 50% from the baseline level throughout the treatment period. The ex vivo platelet adhesion capacity was elevated after the 6-month eltrombopag treatment in both responders and nonresponders. Furthermore, glycoprotein VI (GPVI) expression was significantly upregulated after treatment with eltrombopag. Low-to-intermediate dose of eltrombopag showed good efficacy to expedite platelet production and augment platelet adhesion. These 2 factors might explain the efficacy of eltrombopag in ameliorating hemorrhage in patients with ITP.
authors.affiliation: Department of Hematology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.affiliation: Department of Hematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Kao
authors.affiliation: National Cheng-Kung University Hospital, Tainan, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Pingtung Christian Hospital, Pingtung, Taiwan.
authors.forename: Tsai-Yun
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Keelung Chang-Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Erh-Jung
authors.initials: EJ
authors.lastname: Hsueh
authors.affiliation: Cathay General Hospital, Taipei, Taiwan.
authors.forename: Yii-Jenq
authors.initials: YJ
authors.lastname: Lan
authors.affiliation: Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Yung-Chuan
authors.initials: YC
authors.lastname: Sung
authors.affiliation: China Medical University Hospital, Taichung, Taiwan.
authors.forename: Sheng-Feng
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Institute Molecular Medicine, National Tsing-Hua University, Hsinchu, Taiwan.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Bai
authors.affiliation: Department of Hematology, Mackay Medical College, New Taipei, Taiwan. Electronic address: cgchen@life.nthu.edu.tw.
authors.forename: Caleb G
authors.initials: CG
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; D010980:Platelet Membrane Glycoproteins; D011720:Pyrazoles; C098341:platelet membrane glycoprotein VI; C520809:eltrombopag