Platelet aggregation response in immune thrombocytopenia patients treated with romiplostim
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The thrombopoietin receptor agonist romiplostim is used for the long-term treatment of chronic immune thrombocytopenia (ITP). ITP patients have an increased thrombotic risk, which could be exacerbated if romiplostim increased platelet hyperreactivity or caused spontaneous platelet aggregation. To investigate this possibility, this study examined platelet function in romiplostim-treated ITP patients and healthy subjects. Light transmission platelet aggregometry utilizing arachidonic acid, collagen, epinephrine, ristocetin, ADP, and saline (to assess spontaneous aggregation) was performed for each subject. In addition, the ADP AC50 (ADP concentration that induced half-maximal aggregation) was determined for each patient as a sensitive measurement of altered platelet reactivity. Fifteen ITP patients and 7 healthy subjects entered the study. All ITP patients had active disease and were receiving weekly romiplostim as the sole ITP-directed therapy. Platelet aggregation in response to the strong agonists arachidonic acid, collagen, and ristocetin was not significantly different between ITP patients and healthy subjects (P = 0.2442, P = 0.0548, and P = 0.0879, respectively). Platelet aggregation in response to weak agonists was significantly reduced in ITP patients compared with that in healthy subjects: median (range) aggregation to ADP, 45% (15–84%) versus 89% (70–95%) (P = 0.0010), and epinephrine, 21% (1.6–90%) versus 88% (79–94%) (P = 0.0085). The median AC50 of ADP was threefold higher in ITP patients versus that in healthy subjects (6.3 μM vs 2.1 μM) (P = 0.0049). Significant spontaneous aggregation was not observed in any patient. Platelets from romiplostim-treated ITP patients do not show evidence for spontaneous aggregation or hyperreactivity, but instead have a modestly reduced aggregation response to ADP and epinephrine.
KeywordsPlatelet aggregation Immune thrombocytopenia ITP Romiplostim Thrombosis Thrombopoietin receptor agonist Platelet function testing
H. Al-Samkari analyzed data, created tables and figures, and wrote and revised the manuscript; E. Van Cott analyzed data, wrote a portion of the “Materials and methods” section of the manuscript, and critically revised the manuscript; D. Kuter designed the study, collected and analyzed data, created tables and figures, critically revised the manuscript, and supervised the study.
This study was funded by an unrestricted grant from Amgen, Inc. for performance of platelet aggregation studies (contract number 200712852).
Compliance with ethical standards
Conflict of interest
H. Al-Samkari has a consultancy with Agios. E. Van Cott declares she has no conflict of interest. D. Kuter has received research funding from the following: Protalex, Bristol-Myers Squibb, Rigel, Bioverativ, Agios, Syntimmune, Principia, Alnylam; consultancy with the following: ONO, Pfizer, 3SBios, Eisai, GlaxoSmithKline, Genzyme, Shire, Amgen, Shionogi, Rigel, Syntimmune, MedImmune, Novartis, Bioverativ, Argenx, Zafgen; and does paid expert testimony for Amgen and CRICO.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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