A Review of Romiplostim Mechanism of Action and Clinical Applicability

References

• BusselJ, KulasekararajA, CooperN, et al. Mechanisms and therapeutic prospects of thrombopoietin receptor agonists. Semin Hematol. 2019;56(4):262–278. doi:10.1053/j.seminhematol.2019.09.00131836033
   PubMed Web of Science ®Google Scholar
• KaushanskyK. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115(12):3339–3347. doi:10.1172/JCI2667416322778
   PubMed Web of Science ®Google Scholar
• GhanimaW, CooperN, RodeghieroF, GodeauB, BusselJB. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019;104(6):1112–1123. doi:10.3324/haematol.2018.21284531073079
   PubMed Web of Science ®Google Scholar
• KuterDJ. New thrombopoietic growth factors. Clin Lymphoma Myeloma. 2009;9:S347–S356. doi:10.3816/CLM.2009.s.03419778863
   PubMedGoogle Scholar
• Nplate®. Romiplostim. Thousand Oaks, CA: Amgen Inc.; 2019.
   Google Scholar
• EMA. European Medicines Agency. Romiplostim summary of product characteristics. Available from: https://ec.europa.eu/health/documents/community-register/2021/20210122150420/anx_150420_en.pdf. Accessed 415, 2021.
   Google Scholar
• KuterDJ, BegleyCG. Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. Blood. 2002;100(10):3457–3469. doi:10.1182/blood.V100.10.345712411315
   PubMed Web of Science ®Google Scholar
• KatoT, MatsumotoA, OgamiK, TaharaT, MoritaH, MiyazakiH. Native thrombopoietin: structure and function. Stem Cell. 1998;16(5):322–328. doi:10.1002/stem.160322
   Web of Science ®Google Scholar
• KuterDJ. Milestones in understanding platelet production: a historical overview. Br J Haematol. 2014;165(2):248–258. doi:10.1111/bjh.1278124528208
   PubMed Web of Science ®Google Scholar
• KaushanskyK. Thrombopoietin. N Engl J Med. 1998;339(11):746–754. doi:10.1056/NEJM1998091033911079731092
   PubMed Web of Science ®Google Scholar
• Nakamura-IshizuA, SudaT. Multifaceted roles of thrombopoietin in hematopoietic stem cell regulation. Ann N Y Acad Sci. 2020;1466(1):51–58. doi:10.1111/nyas.1416931292976
   PubMed Web of Science ®Google Scholar
• KaushanskyK, LokS, HollyRD, et al. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature. 1994;369(6481):568–571. doi:10.1038/369568a08202159
   PubMed Web of Science ®Google Scholar
• KuterDJ, BeelerDL, RosenbergRD. The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production. Proc Natl Acad Sci U S A. 1994;91(23):11104–11108. doi:10.1073/pnas.91.23.111047972018
   PubMed Web of Science ®Google Scholar
• BroudyVC, LinNL, KaushanskyK. Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro. Blood. 1995;85(7):1719–1726. doi:10.1182/blood.V85.7.1719.bloodjournal85717197535585
   PubMed Web of Science ®Google Scholar
• KuH, YonemuraY, KaushanskyK, OgawaM. Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice. Blood. 1996;87(11):4544–4551. doi:10.1182/blood.V87.11.4544.bloodjournal871145448639822
   PubMed Web of Science ®Google Scholar
• RaskoJE, O’FlahertyE, BegleyCG. Mpl ligand (MGDF) alone and in combination with stem cell factor (SCF) promotes proliferation and survival of human megakaryocyte, erythroid and granulocyte/macrophage progenitors. Stem Cell. 1997;15(1):33–42. doi:10.1002/stem.150033
   Web of Science ®Google Scholar
• SitnickaE, LinN, PriestleyGV, et al. The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells. Blood. 1996;87(12):4998–5005. doi:10.1182/blood.V87.12.4998.bloodjournal871249988652812
   PubMed Web of Science ®Google Scholar
• LeeJW, LeeSE, JungCW, et al. Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial. Lancet Haematol. 2019;6(11):e562–e572. doi:10.1016/S2352-3026(19)30153-X31474546
   PubMed Web of Science ®Google Scholar
• IshikawaM, MatsudaA, OkamuraD, et al. The progression of severe aplastic anemia to hypoplastic leukemia in a long-term observation after the administration of pegylated rHuMGDF. Hematol Rep. 2018;10(3):7679. doi:10.4081/hr.2018.767930283622
   PubMed Web of Science ®Google Scholar
• de LavalB, PawlikowskaP, BarbieriD, et al. Thrombopoietin promotes NHEJ DNA repair in hematopoietic stem cells through specific activation of Erk and NF-kappaB pathways and their target, IEX-1. Blood. 2014;123(4):509–519. doi:10.1182/blood-2013-07-51587424184684
   PubMed Web of Science ®Google Scholar
• MitchellWB, PinheiroMP, BouladN, et al. Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia. Am J Hematol. 2014;89(12):E228–E234. doi:10.1002/ajh.2383225132654
   PubMed Web of Science ®Google Scholar
• BranehogI, WeinfeldA. Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP) before and during treatment with corticosteroids. Scand J Haematol. 2009;12(1):69–79. doi:10.1111/j.1600-0609.1974.tb00182.x
   Google Scholar
• ChangM, NakagawaPA, WilliamsSA, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood. 2003;102(3):887–895. doi:10.1182/blood-2002-05-147512676790
   PubMed Web of Science ®Google Scholar
• BallemPJ, SegalGM, StrattonJR, GernsheimerT, AdamsonJW, SlichterSJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80(1):33–40. doi:10.1172/JCI1130603597777
   PubMed Web of Science ®Google Scholar
• McMillanR, WangL, TomerA, NicholJ, PistilloJ. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood. 2004;103(4):1364–1369. doi:10.1182/blood-2003-08-26722003-08-267214576051
   PubMed Web of Science ®Google Scholar
• CooperN, GhanimaW. Immune thrombocytopenia. N Engl J Med. 2019;381(10):945–955. doi:10.1056/NEJMcp181047931483965
   PubMed Web of Science ®Google Scholar
• LevPR, GrodzielskiM, GoetteNP, et al. Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism contributing to decreased platelet count. Br J Haematol. 2014;165(6):854–864. doi:10.1111/bjh.1283224673454
   PubMed Web of Science ®Google Scholar
• IraqiM, PerdomoJ, YanF, ChoiPY, ChongBH. Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro. Haematologica. 2015;100(5):623–632. doi:10.3324/haematol.2014.11563425682608
   PubMed Web of Science ®Google Scholar
• van LeeuwenEF, van der VenJT, EngelfrietCP, von Dem BorneAE. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood. 1982;59(1):23–26. doi:10.1182/blood.V59.1.23.237032627
   PubMed Web of Science ®Google Scholar
• NajaouiA, BakchoulT, StoyJ, et al. Autoantibody-mediated complement activation on platelets is a common finding in patients with immune thrombocytopenic purpura (ITP). Eur J Haematol. 2012;88(2):167–174. doi:10.1111/j.1600-0609.2011.01718.x21985182
   PubMed Web of Science ®Google Scholar
• GernsheimerT, StrattonJ, BallemPJ, SlichterSJ. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. N Engl J Med. 1989;320(15):974–980. doi:10.1056/NEJM1989041332015052927480
   PubMed Web of Science ®Google Scholar
• NorrisPAA, SegelGB, BurackWR, et al. FcgammaRI and FcgammaRIII on splenic macrophages mediate phagocytosis of anti-glycoprotein IIb/IIIa autoantibody-opsonized platelets in immune thrombocytopenia. Haematologica. 2020;106(1):250–254. doi:10.3324/haematol.2020.248385
   Web of Science ®Google Scholar
• RochaAM, SouzaC, RochaGA, et al. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica. 2011;96(10):1560–1564. doi:10.3324/haematol.2011.04641721972211
   PubMed Web of Science ®Google Scholar
• RochaAM, SouzaC, RochaGA, et al. The serum levels of the cytokines involved in the Th17 and Th1 cell commitment are increased in individuals with borderline thrombocytopenia. J Hematol Oncol. 2013;6:28. doi:10.1186/1756-8722-6-2823587441
   PubMed Web of Science ®Google Scholar
• StasiR, CooperN, Del PoetaG, et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood. 2008;112(4):1147–1150. doi:10.1182/blood-2007-12-12926218375792
   PubMed Web of Science ®Google Scholar
• ZhangF, ChuX, WangL, et al. Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2006;76(5):427–431. doi:10.1111/j.1600-0609.2005.00622.x16480433
   PubMed Web of Science ®Google Scholar
• TakahashiR, SekineN, NakatakeT. Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Blood. 1999;93(6):1951–1958. doi:10.1182/blood.V93.6.1951.406a33_1951_195810068668
   PubMed Web of Science ®Google Scholar
• HoffmanR, ZaknoenS, YangHH, et al. An antibody cytotoxic to megakaryocyte progenitor cells in a patient with immune thrombocytopenic purpura. N Engl J Med. 1985;312(18):1170–1174. doi:10.1056/NEJM1985050231218074039036
   PubMed Web of Science ®Google Scholar
• SempleJW, MilevY, CosgraveD, et al. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Blood. 1996;87(10):4245–4254. doi:10.1182/blood.V87.10.4245.bloodjournal871042458639783
   PubMed Web of Science ®Google Scholar
• PorcelijnL, HuiskesE, OldertG, SchipperusM, ZwagingaJJ, de HaasM. Detection of platelet autoantibodies to identify immune thrombocytopenia: state of the art. Br J Haematol. 2018;182(3):423–426. doi:10.1111/bjh.1540429808904
   PubMed Web of Science ®Google Scholar
• NewlandA, LeeEJ, McDonaldV, BusselJB. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018;10(1):9–25. doi:10.2217/imt-2017-009728967793
   PubMed Web of Science ®Google Scholar
• Teraz-OroszA, CooperN, CrawleyJTB, SallesC II. Detection of anti-platelet antibodies in immune thrombocytopenia by flow cytometry. Br J Haematol. 2019;184(5):844–847. doi:10.1111/bjh.1518729532906
   PubMed Web of Science ®Google Scholar
• LiS, WangL, ZhaoC, LiL, PengJ, HouM. CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura. Br J Haematol. 2007;139(4):605–611. doi:10.1111/j.1365-2141.2007.06737.x17979946
   PubMed Web of Science ®Google Scholar
• OlssonB, AnderssonPO, JernasM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9(9):1123–1124. doi:10.1038/nm92112937414
   PubMed Web of Science ®Google Scholar
• ChapmanLM, AggreyAA, FieldDJ, et al. Platelets present antigen in the context of MHC class I. J Immunol. 2012;189(2):916–923. doi:10.4049/jimmunol.120058022706078
   PubMed Web of Science ®Google Scholar
• ZuffereyA, SpeckER, MachlusKR, et al. Mature murine megakaryocytes present antigen-MHC class I molecules to T cells and transfer them to platelets. Blood Adv. 2017;1(20):1773–1785. doi:10.1182/bloodadvances.201700702129296823
   PubMed Web of Science ®Google Scholar
• PeerschkeEI, PanickerS, BusselJ. Classical complement pathway activation in immune thrombocytopenia purpura: inhibition by a novel C1s inhibitor. Br J Haematol. 2016;173(6):942–945. doi:10.1111/bjh.1364826305671
   PubMed Web of Science ®Google Scholar
• MasonKD, CarpinelliMR, FletcherJI, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128(6):1173–1186. doi:10.1016/j.cell.2007.01.03717382885
   PubMed Web of Science ®Google Scholar
• QuachME, ChenW, LiR. Mechanisms of platelet clearance and translation to improve platelet storage. Blood. 2018;131(14):1512–1521. doi:10.1182/blood-2017-08-74322929475962
   PubMed Web of Science ®Google Scholar
• QiaoJ, LiuY, LiD, et al. Imbalanced expression of Bcl-xL and Bax in platelets treated with plasma from immune thrombocytopenia. Immunol Res. 2016;64(2):604–609. doi:10.1007/s12026-015-8760-z26712345
   PubMed Web of Science ®Google Scholar
• KuwanaM, OkazakiY, Ikeda. Detection of circulating B cells producing anti-GPIb autoantibodies in patients with immune thrombocytopenia. PLoS One. 2014;9(1):e86943. doi:10.1371/journal.pone.008694324466297
   PubMed Web of Science ®Google Scholar
• GrozovskyR, BegonjaAJ, LiuK, et al. The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling. Nat Med. 2015;21(1):47–54. doi:10.1038/nm.377025485912
   PubMed Web of Science ®Google Scholar
• LevenRM, ClarkB, TablinF. Effect of recombinant interleukin-6 and thrombopoietin on isolated guinea pig bone marrow megakaryocyte protein phosphorylation and proplatelet formation. Blood Cells Mol Dis. 1997;23(2):252–268. doi:10.1006/bcmd.1997.01429410469
   PubMed Web of Science ®Google Scholar
• KaserA, BrandacherG, SteurerW, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood. 2001;98(9):2720–2725. doi:10.1182/blood.v98.9.272011675343
   PubMed Web of Science ®Google Scholar
• EulenfeldR, DittrichA, KhouriC, et al. Interleukin-6 signalling: more than Jaks and STATs. Eur J Cell Biol. 2012;91(6–7):486–495. doi:10.1016/j.ejcb.2011.09.01022138086
   PubMed Web of Science ®Google Scholar
• GrozovskyR, GianniniS, FaletH, HoffmeisterKM. Regulating billions of blood platelets: glycans and beyond. Blood. 2015;126(16):1877–1884. doi:10.1182/blood-2015-01-56912926330242
   PubMed Web of Science ®Google Scholar
• CwirlaSE, BalasubramanianP, DuffinDJ, et al. Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine. Science. 1997;276(5319):1696–1699. doi:10.1126/science.276.5319.16969180079
   PubMed Web of Science ®Google Scholar
• WangB, NicholJL, SullivanJT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76(6):628–638. doi:10.1016/j.clpt.2004.08.01015592334
   PubMed Web of Science ®Google Scholar
• BroudyVC, LinNL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine. 2004;25(2):52–60.14693160
   PubMed Web of Science ®Google Scholar
• KuterDJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013;98(1):10–23. doi:10.1007/s12185-013-1382-023821332
   PubMed Web of Science ®Google Scholar
• BusselJB, KuterDJ, GeorgeJN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355(16):1672–1681. doi:10.1056/NEJMoa05462617050891
   PubMed Web of Science ®Google Scholar
• KuterDJ, BusselJB, LyonsRM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371(9610):395–403. doi:10.1016/S0140-6736(08)60203-218242413
   PubMed Web of Science ®Google Scholar
• KuterDJ, RummelM, BocciaR, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010;363(20):1889–1899. doi:10.1056/NEJMoa100262521067381
   PubMed Web of Science ®Google Scholar
• ShirasugiY, AndoK, MiyazakiK, et al. Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial. Int J Hematol. 2011;94(1):71–80. doi:10.1007/s12185-011-0886-821706145
   PubMed Web of Science ®Google Scholar
• BaoW, BusselJB, HeckS, et al. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood. 2010;116(22):4639–4645. doi:10.1182/blood-2010-04-28171720688957
   PubMed Web of Science ®Google Scholar
• KapurR, AslamR, SpeckER, RebetzJM, SempleJW. Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP). Platelets. 2020;31(3):399–402. doi:10.1080/09537104.2019.162470931146647
   PubMed Web of Science ®Google Scholar
• SchifferliA, NimmerjahnF, KühneT. Immunomodulation in primary immune thrombocytopenia: a possible role of the Fc fragment of romiplostim? Front Immunol. 2019;10:1196. doi:10.3389/fimmu.2019.0119631214173
   PubMed Web of Science ®Google Scholar
• CurraoM, BalduiniCL, BalduiniA, LinB. High doses of romiplostim induce proliferation and reduce proplatelet formation by human megakaryocytes. PLoS One. 2013;8(1):e54723. doi:10.1371/journal.pone.005472323359807
   PubMed Web of Science ®Google Scholar
• RothM, WillB, SimkinG, et al. Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood. 2012;120(2):386–394. doi:10.1182/blood-2011-12-39966722627766
   PubMed Web of Science ®Google Scholar
• WangYM, KrzyzanskiW, DoshiS, XiaoJJ, Perez-RuixoJJ, ChowAT. Pharmacodynamics-mediated drug disposition (PDMDD) and precursor pool lifespan model for single dose of romiplostim in healthy subjects. Validation studies. AAPS J. 2010;12(4):729–740. doi:10.1208/s12248-010-9234-920963535
   PubMed Web of Science ®Google Scholar
• KrzyzanskiW, SutjandraL, Perez-RuixoJJ, SloeyB, ChowAT, WangYM. Pharmacokinetic and pharmacodynamic modeling of romiplostim in animals. Pharm Res. 2013;30(3):655–669. doi:10.1007/s11095-012-0894-223250851
   PubMed Web of Science ®Google Scholar
• NewlandA, CaulierMT, Kappers-KlunneM, et al. An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. Br J Haematol. 2006;135(4):547–553. doi:10.1111/j.1365-2141.2006.06339.x17061981
   PubMed Web of Science ®Google Scholar
• NewlandA, GodeauB, PriegoV, et al. Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol. 2016;172(2):262–273. doi:10.1111/bjh.1382726537623
   PubMed Web of Science ®Google Scholar
• KuterDJ, BusselJB, NewlandA, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411–423. doi:10.1111/bjh.1226023432528
   PubMed Web of Science ®Google Scholar
• BusselJB, KuterDJ, PullarkatV, LyonsRM, GuoM, NicholJL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113(10):2161–2171. doi:10.1182/blood-2008-04-15007818981291
   PubMed Web of Science ®Google Scholar
• CinesDB, WasserJ, RodeghieroF, et al. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017;102(8):1342–1351. doi:10.3324/haematol.2016.16196828411254
   PubMed Web of Science ®Google Scholar
• BusselJB, BuchananGR, NugentDJ, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011;118(1):28–36. doi:10.1182/blood-2010-10-31390821502541
   PubMed Web of Science ®Google Scholar
• TarantinoMD, BusselJB, BlanchetteVS, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10039):45–54. doi:10.1016/s0140-6736(16)00279-827103127
   PubMed Web of Science ®Google Scholar
• TarantinoMD, BusselJB, BlanchetteVS, et al. Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia. Haematologica. 2019;104(11):2283–2291. doi:10.3324/haematol.2018.20228330846500
   PubMed Web of Science ®Google Scholar
• BusselJB, HsiehL, BuchananGR, et al. Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatr Blood Cancer. 2015;62(2):208–213. doi:10.1002/pbc.2513625345874
   PubMed Web of Science ®Google Scholar
• SteurerM, QuittetP, PapadakiHA, et al. A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice. Eur J Haematol. 2017;98(2):112–120. doi:10.1111/ejh.1280727557853
   PubMed Web of Science ®Google Scholar
• DoobareeIU, NewlandA, McDonaldV, et al. Primary immune thrombocytopenia (ITP) treated with romiplostim in routine clinical practice: retrospective study from the United Kingdom ITP registry. Eur J Haematol. 2019;102(5):416–423. doi:10.1111/ejh.1322130758874
   PubMed Web of Science ®Google Scholar
• CarpenedoM, CantoniS, CocciniV, FedeleM, MorraE, PoglianiEM. Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice. Hematol Rep. 2015;7(1):5673. doi:10.4081/hr.2015.567325852848
   PubMed Web of Science ®Google Scholar
• CervinekL, MayerJ, DoubekM. Sustained remission of chronic immune thrombocytopenia after discontinuation of treatment with thrombopoietin-receptor agonists in adults. Int J Hematol. 2015;102(1):7–11. doi:10.1007/s12185-015-1793-125833724
   PubMed Web of Science ®Google Scholar
• GhadakiB, NaziI, KeltonJG, ArnoldDM. Sustained remissions of immune thrombocytopenia associated with the use of thrombopoietin receptor agonists. Transfusion. 2013;53(11):2807–2812. doi:10.1111/trf.1213923451917
   PubMed Web of Science ®Google Scholar
• Mingot-CastellanoME, Grande-GarciaC, Valcarcel-FerreirasD, Conill-CortesC, de Olivar-oliverL. Sustained remission in patients with primary immune thrombocytopenia after romiplostim tapering and discontinuation: a case series in real life management in Spain. Case Rep Hematol. 2017;2017:4109605. doi:10.1155/2017/410960528695025
   PubMed Web of Science ®Google Scholar
• LozanoML, Mingot-CastellanoME, PereraMM, et al. Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia. Sci Rep. 2019;9(1):16680. doi:10.1038/s41598-019-53209-y31723222
   PubMed Web of Science ®Google Scholar
• WangM, QinP, ZhouH, et al. Recombinant human thrombopoietin (rhTPO) and high-dose dexamethasone (HD-DXM) versus high-dose dexamethasone monotherapy as frontline treatment in newly diagnosed adult immune thrombocytopenia (ITP): a prospective, multicentre, randomised, controlled trial. Blood. 2017;130(suppl 1):13. doi:10.1182/blood.V130.Suppl_1.13.13
   Google Scholar
• CinesDB, GernsheimerT, WasserJ, et al. Integrated analysis of long-term safety in patients with chronic immune thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist romiplostim. Int J Hematol. 2015;102(3):259–270. doi:10.1007/s12185-015-1837-626201709
   PubMed Web of Science ®Google Scholar
• GraingerJ, BusselJ, TarantinoM, et al. Updated results from the single-arm, open-label, long-term efficacy and safety study of subcutaneous (SC) romiplostim in children with immune thrombocytopenia (ITP). Blood. 2019;134(Suppl1):1095. doi:10.1182/blood-2019-13124131409673
   PubMed Web of Science ®Google Scholar
• WongRSM, SalehMN, KhelifA, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527–2536. doi:10.1182/blood-2017-04-74870729042367
   PubMed Web of Science ®Google Scholar
• GhanimaW, JunkerP, HasselbalchHC, et al. Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents. Br J Haematol. 2011;155(2):248–255. doi:10.1111/j.1365-2141.2011.08845.x21902682
   PubMed Web of Science ®Google Scholar
• RodeghieroF, StasiR, GiagounidisA, et al. Long-term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials. Eur J Haematol. 2013;91:423–436. doi:10.1111/ejh.1218123927437
   PubMedGoogle Scholar
• KuterDJ, MuftiGJ, BainBJ, HasserjianRP, DavisW, RutsteinM. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood. 2009;114(18):3748–3756. doi:10.1182/blood-2009-05-22476619671919
   PubMed Web of Science ®Google Scholar
• LozanoML, Mingot-CastellanoME, PereraM, et al. Predictive factors for thrombopoietin receptor agonist free responses in chronic ITP patients: a multicenter retrospective study with long-term follow-up. Blood. 2019;134(suppl 1):2370. doi:10.1182/blood-2019-125580
   Web of Science ®Google Scholar
• CukerA, PrakET, CinesDB. Can immune thrombocytopenia be cured with medical therapy? Semin Thromb Hemost. 2015;41(4):395–404. doi:10.1055/s-0034-154400125793364
   PubMed Web of Science ®Google Scholar
• Gómez-AlmaguerD, Herrera-RojasMA, Jaime-PérezJC, et al. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014;123(25):3906–3908. doi:10.1182/blood-2014-01-54936024802773
   PubMed Web of Science ®Google Scholar
• GudbrandsdottirS, BirgensHS, FrederiksenH, et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013;121(11):1976–1981. doi:10.1182/blood-2012-09-45569123293082
   PubMed Web of Science ®Google Scholar
• ZajaF, BaccaraniM, MazzaP, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood. 2010;115(14):2755–2762. doi:10.1182/blood-2009-07-22981520130241
   PubMed Web of Science ®Google Scholar
• NewlandA, BusselJB, BirdR, et al. Predictors of remission in adults with immune thrombocytopenia (ITP) treated with romiplostim. Blood. 2018;132(Supplement 1):735. doi:10.1182/blood-2018-99-10979129945953
   PubMed Web of Science ®Google Scholar
• BusselJB, WangX, LopezA, EisenM. Case study of remission in adults with immune thrombocytopenia following cessation of treatment with the thrombopoietin mimetic romiplostim. Hematology. 2016;21(4):257–262. doi:10.1179/1607845415y.000000004126251926
   PubMed Web of Science ®Google Scholar
• KuterDJ, NewlandA, ChongBH, et al. Romiplostim in adult patients with newly diagnosed or persistent immune thrombocytopenia (ITP) for up to 1 year and in those with chronic ITP for more than 1 year: a subgroup analysis of integrated data from completed romiplostim studies. Br J Haematol. 2019;185(3):503–513. doi:10.1111/bjh.1580330793285
   PubMed Web of Science ®Google Scholar
• SchifferliA, HolbroA, ChitlurM, et al. A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up. Am J Hematol. 2018;93(6):751–759. doi:10.1002/ajh.2508629516627
   PubMed Web of Science ®Google Scholar
• KuterDJ. Managing thrombocytopenia associated with cancer chemotherapy. Oncology. 2015;29(4):282–294.25952492
   PubMed Web of Science ®Google Scholar
• WeyckerD, HatfieldM, GrossmanA, et al. Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice. BMC Cancer. 2019;19(1):151. doi:10.1186/s12885-019-5354-530764783
   PubMed Web of Science ®Google Scholar
• DenduluriN, PattDA, WangY, et al. Dose delays, dose reductions, and relative dose intensity in patients with cancer who received adjuvant or neoadjuvant chemotherapy in community oncology practices. J Natl Compr Canc Netw. 2015;13(11):1383–1393. doi:10.6004/jnccn.2015.016626553767
   PubMed Web of Science ®Google Scholar
• LymanGH, DaleDC, TomitaD, WhittakerS, CrawfordJ. A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting. Breast Cancer Res Treat. 2013;139(3):863–872. doi:10.1007/s10549-013-2582-223771731
   PubMed Web of Science ®Google Scholar
• GernsheimerTB, BrownSB, TriulziDJ, et al. Effects of tranexamic acid prophylaxis on bleeding outcomes in hematologic malignancy: the a-TREAT trial. Blood. 2020;136(Supplement 1):1–2. doi:10.1182/blood-2020-13892032430499
   PubMed Web of Science ®Google Scholar
• McElroyPL, WeiP, BuckK, et al. Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia. Exp Hematol. 2015;43(6):479–487. doi:10.1016/j.exphem.2015.02.00425754671
   PubMed Web of Science ®Google Scholar
• DemeterJ, IstenesI, FodorA, et al. Efficacy of romiplostim in the treatment of chemotherapy induced thrombocytopenia (CIT) in a patient with mantle cell lymphoma. Case reports. Pathol Oncol Res. 2011;17(1):141–143. doi:10.1007/s12253-010-9276-420628840
   PubMed Web of Science ®Google Scholar
• JacobsonAE, ShahN, SettyBA. Romiplostim for therapy-related thrombocytopenia in pediatric malignancies [Brief report]. Pediatr Blood Cancer. 2017;64(8):e26473. doi:10.1002/pbc.26473
   Web of Science ®Google Scholar
• Al-SamkariH, MarshallAL, GoodarziK, KuterDJ. The use of romiplostim in treating chemotherapy-induced thrombocytopenia in patients with solid tumors. Haematologica. 2018;103(4):e169–e172. doi:10.3324/haematol.2017.18016629242295
   PubMed Web of Science ®Google Scholar
• ParameswaranR, LunningM, ManthaS, et al. Romiplostim for management of chemotherapy-induced thrombocytopenia. Support Care Cancer. 2014;22(5):1217–1222. doi:10.1007/s00520-013-2074-224414994
   PubMed Web of Science ®Google Scholar
• DardisC, MiltonK, PatelN. Thrombopoietin receptor agonists are effective in treating chemotherapy-induced thrombocytopenia in patients with gliomas undergoing myelotoxic treatment. Oncomedicine. 2017;2:37–41. doi:10.7150/oncm.17909
   Google Scholar
• Entrena UreñaL, Fernandez JimenezD, Mesa MoralesZ, Hernandez MohedoF, Jurado ChaconM. The role of romiplostim in chemotherapy-induced thrombocytopenia treatment. Haematologica. 2016;101:590.
   Web of Science ®Google Scholar
• FanaleM, StiffP, NoonanK, McCoyJ, RutsteinM, MoskowitzC. Safety of romiplostim for treatment of severe chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma receiving multi-cycle chemotherapy: results from an open-label dose- and schedule-finding study. Eur J Cancer. 2009;7(2–3):563. doi:10.1016/S1359-6349(09)71900-7
   Web of Science ®Google Scholar
• SoffGA, MiaoY, BendheimG, et al. Romiplostim treatment of chemotherapy-induced thrombocytopenia. J Clin Oncol. 2019;37(31):2892–2898. doi:10.1200/JCO.18.0193131545663
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Study of romiplostim for chemotherapy-induced thrombocytopenia in adult subjects with non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer (NCT03937154). Available from: https://clinicaltrials.gov/ct2/show/NCT03937154. Accessed 79, 2019.
   Google Scholar
• ClinicalTrials.gov. Study of romiplostim for chemotherapy induced thrombocytopenia (NCT02052882). Available from: https://clinicaltrials.gov/ct2/show/NCT02052882. Accessed 79, 2019.
   Google Scholar
• ClinicalTrials.gov. Study of romiplostim for chemo-induced thrombocytopenia in adults subjects with gastrointestinal or colorectal cancer (NCT03362177). Available from: https://clinicaltrials.gov/ct2/show/NCT03362177. Accessed 726, 2019.
   Google Scholar
• Al-SamkariH, ParnesAD, GoodarziK, WeitzmanJI, ConnorsJM, KuterDJ. A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies. Haematologica. 2020. doi:10.3324/haematol.2020.251900
   Web of Science ®Google Scholar
• SoffGA, Ray-CoquardI, Marfil-RiveraLJ, et al. Literature review of TPOR agonists for CIT [abstract 1563P]. Ann Oncol. 2017;28(suppl 5):mdx388. doi:10.1093/annonc/mdx388.023
   Google Scholar
• KaushanskyK, LichtmanMA, PrchalJT, et al. Williams Hematology. 9th ed. McGraw-Hill; 2016.
   Google Scholar
• MarshJC. Bone marrow failure syndromes. Clin Med. 2005;5(4):332–336. doi:10.7861/clinmedicine.5-4-332
   Web of Science ®Google Scholar
• MarshJC, GibsonFM, PrueRL, et al. Serum thrombopoietin levels in patients with aplastic anaemia. Br J Haematol. 1996;95(4):605–610. doi:10.1046/j.1365-2141.1996.d01-1966.x8982033
   PubMed Web of Science ®Google Scholar
• KojimaS, MatsuyamaT, KoderaY, TaharaT, KatoT. Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme-linked immunosorbent assay. Br J Haematol. 1997;97(3):538–543. doi:10.1046/j.1365-2141.1997.992915.x9207395
   PubMed Web of Science ®Google Scholar
• NicholJL. Endogenous TPO (eTPO) levels in health and disease: possible clues for therapeutic intervention. Stem Cell. 1998;16(Suppl 2):165–175. doi:10.1002/stem.5530160719
   PubMedGoogle Scholar
• YoungNS. Aplastic anemia. N Engl J Med. 2018;379(17):1643–1656. doi:10.1056/NEJMra141348530354958
   PubMed Web of Science ®Google Scholar
• Promacta®. Eltrombopag. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019.
   Google Scholar
• TomiyamaY, JangJH, LeeJ-W, et al. Efficacy and safety of romiplostim in patients with acquired aplastic anemia ineligible or refractory to immunosuppressive therapy: interim analysis of phase 2/3 clinical trial. Blood. 2018;132(Supplement 1):1306. doi:10.1182/blood-2018-99-112478
   Web of Science ®Google Scholar
• JangJH, TomiyamaY, MiyazakiK, et al. Efficacy and safety of romiplostim in refractory aplastic anaemia: a phase II/III, multicentre, open-label study. Br J Haematol. 2021;192(1):190–199. doi:10.1111/bjh.1719033152120
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Study of AMG531(Romiplostim) in patients with aplastic anemia (NCT03957694). Available from: https://clinicaltrials.gov/ct2/show/NCT03957694. Accessed 1218, 2020.
   Google Scholar
• ClinicalTrials.gov. Study of AMG531 (Romiplostim) in patients with aplastic anemia (NCT04095936). Available from: https://clinicaltrials.gov/ct2/show/NCT04095936. Accessed 1218, 2020.
   Google Scholar
• ZhaoLP, Sicre De FontbruneF, ContejeanA, et al. Nationwide survey in France on the use of romiplostim in patients with refractory severe aplastic anemia. Bone Marrow Transplant. 2019;54(7):1161–1163. doi:10.1038/s41409-019-0452-130670823
   PubMed Web of Science ®Google Scholar
• HosokawaK, YamazakiH, TanabeM, ImiT, SugimoriN, NakaoS. High-dose romiplostim accelerates hematologic recovery in patients with aplastic anemia refractory to eltrombopag. Leukemia. 2021;35(3):906–909. doi:10.1038/s41375-020-0950-632616921
   PubMed Web of Science ®Google Scholar
• IseM, IizukaH, KamodaY, HiraoM, KidaM, UsukiK. Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study. Int J Hematol. 2020;112(6):787–794. doi:10.1007/s12185-020-02971-132876852
   PubMed Web of Science ®Google Scholar
• AlvaradoLJ, AndreoniA, HuntsmanHD, ChengH, KnutsonJR, LarochelleA. Heterodimerization of TPO and IFNγ impairs human hematopoietic stem/progenitor cell signaling and survival in chronic inflammation. Blood. 2017;130(suppl 1):4. doi:10.1182/blood.V130.Suppl_1.4.428684446
   PubMed Web of Science ®Google Scholar
• AlvaradoLJ, HuntsmanHD, ChengH, et al. Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-gamma. Blood. 2019;133(19):2043–2055. doi:10.1182/blood-2018-11-88448630803992
   PubMed Web of Science ®Google Scholar
• KimMJ, ParkSH, OpellaSJ, et al. NMR structural studies of interactions of a small, nonpeptidyl Tpo mimic with the thrombopoietin receptor extracellular juxtamembrane and transmembrane domains. J Biol Chem. 2007;282(19):14253–14261. doi:10.1074/jbc.M61161620017369254
   PubMed Web of Science ®Google Scholar
• Erickson-MillerCL, DelormeE, TianSS, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cell. 2009;27(2):424–430. doi:10.1634/stemcells.2008-0366
   PubMed Web of Science ®Google Scholar
• ScheinbergP. Stem cell stimulation continues to pay off in aplastic anaemia. Lancet Haematol. 2019;6(11):e543–e544. doi:10.1016/S2352-3026(19)30181-431474547
   PubMed Web of Science ®Google Scholar
• BuninDI, BakkeJ, GreenCE, JavitzHS, FieldenM, ChangPY. Romiplostim (Nplate®) as an effective radiation countermeasure to improve survival and platelet recovery in mice. Int J Radiat Biol. 2019;96(1):145–154. doi:10.1080/09553002.2019.160546531021662
   PubMed Web of Science ®Google Scholar
• YamaguchiM, HirouchiT, YokoyamaK, NishiyamaA, MurakamiS, KashiwakuraI. The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation. Sci Rep. 2018;8(1):10659. doi:10.1038/s41598-018-29013-530006622
   PubMed Web of Science ®Google Scholar
• YamaguchiM, HirouchiT, YoshiokaH, WatanabeJ, KashiwakuraI. Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation. Free Radic Biol Med. 2019;136:60–75. doi:10.1016/j.freeradbiomed.2019.03.02330926566
   PubMed Web of Science ®Google Scholar
• HirouchiT, ItoK, NakanoM, et al. Mitigative effects of a combination of multiple pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation. Curr Pharm Biotechnol. 2015;17(2):190–199. doi:10.2174/138920101666615082612533126306743
   PubMed Web of Science ®Google Scholar
• MonzenS, KimuraS, YamaguchiM, KashiwakuraI. Protective effect of the c-mpl agonist romiplostim on megakaryocytopoiesis of human CD34(+) hematopoietic progenitor cells exposed to ionizing radiation. J Interferon Cytokine Res. 2018;38(5):206–212. doi:10.1089/jir.2017.010429708814
   PubMed Web of Science ®Google Scholar
• WongK, ChangPY, FieldenM, et al. Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. Int J Radiat Biol. 2019:1–12. doi:10.1080/09553002.2019.1625488
   Web of Science ®Google Scholar
• Al-SamkariH, MarshallAL, GoodarziK, KuterDJ. Romiplostim for the management of perioperative thrombocytopenia. Br J Haematol. 2018;182(1):106–113. doi:10.1111/bjh.1528029767837
   PubMed Web of Science ®Google Scholar
• MarshallAL, GoodarziK, KuterDJ. Romiplostim in the management of the thrombocytopenic surgical patient. Transfusion. 2015;55(10):2505–2510. doi:10.1111/trf.1318126033367
   PubMed Web of Science ®Google Scholar
• ColtoffA, ShreenivasA, AfsharS, SteinbergA. A single-institution experience of performing bloodless transplant in Jehovah’s witness patients. Hematol Oncol Stem Cell Ther. 2019;12(1):44–49. doi:10.1016/j.hemonc.2018.11.00330605629
   PubMedGoogle Scholar
• MoussaMM, MowafyN. Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis. Research support, non-U.S. Gov’t. J Gastroenterol Hepatol. 2013;28(2):335–341. doi:10.1111/j.1440-1746.2012.07246.x22849409
   PubMed Web of Science ®Google Scholar
• ArnoldDM, HeddleNM, CookRJ, et al. Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial. Lancet Haematol. 2020;7(9):e640–e648. doi:10.1016/S2352-3026(20)30227-132853584
   PubMed Web of Science ®Google Scholar
• BusselJB, KuterD. Preparing patients with immune thrombocytopenia for surgery: what are the options? Lancet Haematol. 2020;7(9):e626–e627. doi:10.1016/S2352-3026(20)30253-232853578
   PubMed Web of Science ®Google Scholar
• PulanicD, LozierJN, PavleticSZ. Thrombocytopenia and hemostatic disorders in chronic graft versus host disease. Bone Marrow Transplant. 2009;44(7):393–403. doi:10.1038/bmt.2009.19619684626
   PubMed Web of Science ®Google Scholar
• NashRA, GooleyT, DavisC, AppelbaumFR. The problem of thrombocytopenia after hematopoietic stem cell transplantation. Oncologist. 1996;1(6):371–380. doi:10.1634/theoncologist.1-6-37110388019
   PubMedGoogle Scholar
• MichniackiTF, EbensCL, ChoiSW. Immune-mediated cytopenias after hematopoietic cell transplantation: pathophysiology, clinical manifestations, diagnosis, and treatment strategies. Curr Oncol Rep. 2019;21(10):87. doi:10.1007/s11912-019-0838-731414187
   PubMed Web of Science ®Google Scholar
• ChoiCM, SchmaierAH, SnellMR, LazarusHM. Thrombotic microangiopathy in haematopoietic stem cell transplantation: diagnosis and treatment. Drugs. 2009;69(2):183–198. doi:10.2165/00003495-200969020-0000419228075
   PubMed Web of Science ®Google Scholar
• BrunoB, GooleyT, SullivanKM, et al. Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(3):154–162. doi:10.1053/bbmt.2001.v7.pm1130254911302549
   PubMed Web of Science ®Google Scholar
• BolwellB, PohlmanB, SobecksR, et al. Prognostic importance of the platelet count 100 days post allogeneic bone marrow transplant. Bone Marrow Transplant. 2004;33(4):419–423. doi:10.1038/sj.bmt.170433014688814
   PubMed Web of Science ®Google Scholar
• KuzminaZ, EderS, BohmA, et al. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study. Leukemia. 2012;26(4):746–756. doi:10.1038/leu.2011.25721926960
   PubMed Web of Science ®Google Scholar
• ZajaF, GerominA, PatriarcaF, et al. Prognostic significance of delayed thrombocytopenia after allogeneic stem cell transplant. Am J Hematol. 2011;86(9):790–792. doi:10.1002/ajh.2208621830231
   PubMed Web of Science ®Google Scholar
• BentoL, BastidaJM, Garcia-CadenasI, et al. Thrombopoietin receptor agonists for severe thrombocytopenia after allogeneic stem cell transplantation: experience of the Spanish Group of hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2019;25(9):1825–1831. doi:10.1016/j.bbmt.2019.05.02331152794
   PubMed Web of Science ®Google Scholar
• FominykhM, VoloshinS, SchmidtA, et al. Romiplostim after hematopoietic stem cell transplantation: results of a pilot study. Haematologica. 2012;97:397.
   Google Scholar
• RiveraD, BastidaJM, CorralLL, et al. Usefulness of thrombopoietin receptor agonists for thrombocytopenia after allogeneic stem cell transplantation. An eight-year single center experience. Blood. 2017;130(suppl 1):3222.
   Google Scholar
• XueE, LawrenceT, GernsheimerTB, MilanoF. Retrospective evaluation of the use of romiplostim after hematopoietic stem cell transplantation. Blood. 2019;134(suppl 1):5660. doi:10.1182/blood-2019-128673
   Web of Science ®Google Scholar
• PoonLM, Di StasiA, PopatU, ChamplinRE, CiureaSO. Romiplostim for delayed platelet recovery and secondary thrombocytopenia following allogeneic stem cell transplantation. Am J Blood Res. 2013;3(3):260–264.23997988
   PubMedGoogle Scholar
• BattipagliaG, RuggeriA, BrissotE, et al. Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation. Bone Marrow Transplant. 2015;50(12):1574–1577. doi:10.1038/bmt.2015.18226281029
   PubMed Web of Science ®Google Scholar
• ChristakopoulasGE, DeForTE, HageSM, et al. Romiplostim improves platelet recovery after UCB transplant [abstract no. 1979]. Blood. 2019;134(Supplement_1):1979. doi:10.1182/blood-2019-125424
   Web of Science ®Google Scholar
• Peffault de LatourR, ChevretS, RuggeriAL, et al. Romiplostim in patients undergoing hematopoietic stem cell transplantation: results of a phase 1/2 multicenter trial. Blood. 2020;135(3):227–229. doi:10.1182/blood.201900035831805185
   PubMed Web of Science ®Google Scholar
• MahatU, RotzSJ, HannaR. Use of thrombopoietin receptor agonists in prolonged thrombocytopenia after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2020;26(3):e65–e73. doi:10.1016/j.bbmt.2019.12.00331830528
   PubMedGoogle Scholar
• BuchbinderD, HsiehL, KranceR, NugentDJ. Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease. Pediatr Transplant. 2014;18(7):E252–E254. doi:10.1111/petr.1232525118016
   PubMed Web of Science ®Google Scholar
• LiS, WuR, WangB, et al. Eltrombopag for delayed platelet recovery and secondary thrombocytopenia following allogeneic stem cell transplantation in children. J Pediatr Hematol Oncol. 2019;41(1):38–41. doi:10.1097/MPH.000000000000126330080752
   PubMed Web of Science ®Google Scholar
• MasettiR, VendeminiF, QuarelloP, et al. Eltrombopag for thrombocytopenia following allogeneic hematopoietic stem cell transplantation in children. Pediatr Blood Cancer. 2020;67(5):e28208. doi:10.1002/pbc.2820832065469
   PubMed Web of Science ®Google Scholar
• MaximovaN, ZanonD, RovereF, MaestroA, SchillaniG, PaparazzoR. Romiplostim for secondary thrombocytopenia following allogeneic stem cell transplantation in children. Int J Hematol. 2015;102(5):626–632. doi:10.1007/s12185-015-1821-126084627
   PubMed Web of Science ®Google Scholar
• UekiH, IgarashiS, KimuraS, et al. Evans syndrome after unrelated bone marrow transplantation for refractory cytopenia of childhood. Pediatr Transplant. 2014;18(7):E246–E251. doi:10.1111/petr.1232325074497
   PubMed Web of Science ®Google Scholar
• GropperS, AlthausK, NajmJ, et al. A patient with Fechtner syndrome successfully treated with romiplostim. Case reports letter. Thromb Haemost. 2012;107(3):590–591. doi:10.1160/TH11-07-047422273764
   PubMed Web of Science ®Google Scholar
• YamanouchiJ, HatoT, KunishimaS, NiiyaT, NakamuraH, YasukawaM. A novel MYH9 mutation in a patient with MYH9 disorders and platelet size-specific effect of romiplostim on macrothrombocytopenia. Ann Hematol. 2015;94(9):1599–1600. doi:10.1007/s00277-015-2416-x26051904
   PubMed Web of Science ®Google Scholar
• PecciA, RagabI, BozziV, et al. Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim. EMBO Mol Med. 2018;10(1):63–75. doi:10.15252/emmm.20170816829191945
   PubMed Web of Science ®Google Scholar
• SeoA, Ben-HaroshM, SirinM, et al. Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin. Blood. 2017;130(7):875–880. doi:10.1182/blood-2017-02-76803628559357
   PubMed Web of Science ®Google Scholar
• PecciA, GreseleP, KlersyC, et al. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood. 2010;116(26):5832–5837. doi:10.1182/blood-2010-08-30472520844233
   PubMed Web of Science ®Google Scholar
• ZaninettiC, GreseleP, BertomoroA, et al. Eltrombopag for the treatment of inherited thrombocytopenias: a Phase II clinical trial. Haematologica. 2020;105(3):820–828. doi:10.3324/haematol.2019.22396631273088
   PubMed Web of Science ®Google Scholar
• NeunertCE, RoseMJ. Romiplostim for the management of pediatric immune thrombocytopenia: drug development and current practice. Blood Adv. 2019;3(12):1907–1915. doi:10.1182/bloodadvances.201900027931239245
   PubMed Web of Science ®Google Scholar
• Van HelmondJ, GaneshJ, AhmedR. Atypical presentation of Wiskott Aldrich syndrome in an infant [abstract]. Pediatr Blood Cancer. 2019;66(S1):S228–S229.
   Google Scholar
• GerritsAJ, LevenEA, FrelingerAL 3rd, et al. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood. 2015;126(11):1367–1378. doi:10.1182/blood-2014-09-60257326224646
   PubMed Web of Science ®Google Scholar
• DusheikoG. Thrombopoietin agonists for the treatment of thrombocytopenia in liver disease and hepatitis C. Clin Liver Dis. 2009;13(3):487–501. doi:10.1016/j.cld.2009.05.01219628164
   PubMed Web of Science ®Google Scholar
• DOPTELET®. Avatrombopag. Durham, NC: AkaRx, Inc.; 2020.
   Google Scholar
• MULPLETA®. Lusutrombopag Tablets. Florham Park, NJ: Shionogi Inc.; 2020.
   Google Scholar
• CastelloteJ, GirbauA, ArajolC, XiolX. Romiplostim in chronic liver disease with severe thrombocytopenia undergoing an elective invasive procedure. Case reports letter. Rev Esp Enferm Dig. 2011;103(10):556. doi:10.4321/S1130-0108201100100001522054278
   PubMed Web of Science ®Google Scholar
• VoicanCS, NaveauS, PerlemuterG. Successful antiviral therapy for hepatitis C virus-induced cirrhosis after an increase in the platelet count with romiplostim: two case reports. Eur J Gastroenterol Hepatol. 2012;24(12):1455–1458. doi:10.1097/MEG.0b013e328357d5f222890208
   PubMed Web of Science ®Google Scholar
• SteensmaDP. Myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2015;90(7):969–983. doi:10.1016/j.mayocp.2015.04.00126141335
   PubMed Web of Science ®Google Scholar
• BasoodM, OsterHS, MittelmanM. Thrombocytopenia in patients with myelodysplastic syndromes: still an unsolved problem. Mediterr J Hematol Infect Dis. 2018;10(1):e2018046. doi:10.4084/MJHID.2018.04630002802
   PubMed Web of Science ®Google Scholar
• SteensmaDP. Myelodysplastic syndromes current treatment algorithm 2018. Blood Cancer J. 2018;8(5):47. doi:10.1038/s41408-018-0085-429795386
   PubMed Web of Science ®Google Scholar
• KantarjianHM, FenauxP, SekeresMA, et al. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol. 2018;5(3):e117–e126. doi:10.1016/S2352-3026(18)30016-429396092
   PubMed Web of Science ®Google Scholar
• DodilletH, KreuzerKA, MonsefI, SkoetzN. Thrombopoietin mimetics for patients with myelodysplastic syndromes. Cochrane Database Syst Rev. 2017;9:CD009883. doi:10.1002/14651858.CD009883.pub228962071
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. A pilot study of a thrombopoietin-receptor agonist, eltrombopag, in patients with low to int-2 risk myelodysplastic syndrome (MDS) (NCT00961064). Available from: https://clinicaltrials.gov/ct2/show/NCT00961064. Accessed 1110, 2020.
   Google Scholar
• ClinicalTrials.gov. Validation of a predictive model of response to romiplostim in patients with IPSS low or intermediate-1 risk MDS and thrombocytopenia (Europe) (NCT02335268). Available from: https://clinicaltrials.gov/ct2/show/NCT02335268. Accessed 1110, 2020.
   Google Scholar
• ClinicalTrials.gov. TPO-mimetic use in children for hemotopoietic failure (NCT04478227). Available from: https://clinicaltrials.gov/ct2/show/NCT04478227. Accessed 1110, 2020.
   Google Scholar
• GreenbergPL, Garcia-ManeroG, MooreM, et al. A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving decitabine. Research support, non-U.S. Gov’t. Leuk Lymphoma. 2013;54(2):321–328. doi:10.3109/10428194.2012.71347722906162
   PubMed Web of Science ®Google Scholar
• GiagounidisA, MuftiGJ, FenauxP, et al. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer. 2014;120(12):1838–1846. doi:10.1002/cncr.2866324706489
   PubMed Web of Science ®Google Scholar
• BusselJB, KuterDJ, AledortLM, et al. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014;123(25):3887–3894. doi:10.1182/blood-2013-07-51439824802775
   PubMed Web of Science ®Google Scholar
• KuterDJ, TarantinoMD, LawrenceT. Clinical overview and practical considerations for optimizing romiplostim therapy in patients with immune thrombocytopenia. Blood Rev. 2021;100811. doi:10.1016/j.blre.2021.10081133781612
   PubMed Web of Science ®Google Scholar
• JanssensA, TarantinoM, BirdRJ, et al. Romiplostim treatment in adults with immune thrombocytopenia of varying duration and severity. Acta Haematol. 2015;134(4):215–228. doi:10.1159/00038165726066765
   PubMed Web of Science ®Google Scholar