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P.17 掲載の参考文献

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• 6) 坂本明彦, 加藤尚志, 船津高志:細胞膜上におけるトロンボポエチン受容体の一分子ダイナミクス. 生化学 83:912-919, 2011

• 7) Feese MD, Tamada T, Kato Y et al:Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing anti-body fragment. Proc Natl Acad Sci USA 101:1816-1821, 2004

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• 10) Tong W, Ibarra YM, Lodish HF:Signals emanating from the membrane proximal region of the thrombo-poietn receptor(mpl)support hematopoietic stem cell self-renewal. Exp Hematol 35:1447-1455, 2007

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• 13) Ichikawa M, Asai T, Saito T et al:AML-1 is required for megakaryocytic maturation and lymphocytic dif-ferentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat Med 10:299-304, 2004

• 14) Hart A, Melet F, Grossfeld P et al:Fli-1 is required for murine vascular and megakaryocytic develop-ment and is hemizygously deleted in patients with thrombocytopenia. Immunity 13:167-177, 2000

• 15) Garzon R, Pichiorri F, Palumbo T et al:MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci USA 103:5078-5083, 2006
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• 16) Zhang L, Sankaran VG, Lodish HF:MicroRNAs in erythroid and megakaryocytic differentiation and megakaryocyte-erythroid progenitor lineage commitment. Leukemia:[Epub ahead of print], 2012

• 17) Motohashi H, Kimura M, Fujita R et al:NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation. Blood 115:677-686, 2010
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• 18) Josefsson EC, James C, Henley KJ et al:Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets. J Exp Med 208:2017-2031, 2011
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• 19) White MJ, Schoenwaelder SM, Josefsson EC et al:Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function. Blood 119:4283-4290, 2012
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• 20) Raslova H, Kauffmann A, Sekkai D et al:Interrelation between polyploidization and megakaryocyte differentiation:a gene profiling approach. Blood 109:3225-3234, 2007
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• 21) Kamatani Y, Matsuda K, Okada Y et al:Genomewide association study of hematological and biochemical traits in a Japanese population. Nat Genet 42:210-215, 2010

• 22) Gieger C, Radhakrishnan A, Cvejic A et al:New gene functions in megakaryopoiesis and platelet formation. Nature 480:201-208, 2011
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• 23) Khandekar G, Kim S, Jagadeeswaran P:Zebrafish thrombocytes:functions and origins. Adv Hematol 2012:857058, 2012
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• 24) Hagiwara T, Kodama I, Horie K et al:Proliferative properties of human umbilical cord blood megakaryocyte progenitor cells to human thrombopoietin. Exp Hematol 26:228-235, 1998
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• 25) Eto K, Murphy R, Kerrigan SW et al:Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling. Proc Natl Acad Sci USA 99:12819-12824, 2002
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• 26) Nakamura S, Takayama N, Nakauchi H et al:Platelet production system using an immortalized megakaryocyte cell line derived from human pluripotent stem cells. 53rd ASH Annual Meeting Abstr, 2011

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• 30) Thon JN, Montalvo A, Patel-Hett S et al:Cytoskeletal mechanics of proplatelet maturation and platelet release. J Cell Biol 191:861-874, 2010
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• 31) Fuentes R, Wang Y, Hirsch J et al:Infusion of mature megakaryocytes into mice yields functional platelets. J Clin Invest 120:3917-3922, 2010
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• 32) Levin J:The Evolution of Mammalian Platelets. In:Platelets, Second Edition, ed by Michelson AD, Academic Press, San Diego, 2007, pp.3-22

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P.29 掲載の参考文献

• 1) Kato T, Ogami K, Shimada Y et al:Purification and characterization of thrombopoietin. J Biochem 118:229-236, 1995
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• 2) Sohma Y, Akahori H, Seki N et al:Molecular cloning and chromosomal localization of the human thrombo-poietin gene. FEBS Lett 353:57-61, 1994

• 3) Kuter DJ, Beeler DL, Rosenberg RD:The purification of megapoietin:a physiological regulator of mega-karyocyte growth and platelet production. Proc Natl Acad Sci USA 91:11104-11108, 1994

• 4) de Sauvage FJ, Hass PE, Spencer SD et al:Stimula-tion of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 369:533-538, 1994

• 5) Lok S, Kaushansky K, Holly RD et al:Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 369:565-568, 1994
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• 6) Kaushansky K, Lok S, Holly RD et al:Promotion of megakaryocyte progenitor expansion and differentia-tion by the c-Mpl ligand thrombopoietin. Nature 369:568-571, 1994

• 7) Bartley TD, Bogenberger J, Hunt P et al:Identifica-tion and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 77:1117-1124, 1994

• 8) Komatsu N, Okamoto T, Yoshida T et al:Pegylated recombinant human megakaryocyte growth and development factor(PEG-rHuMGDF)increased platelet counts(PLT)in patients(pts)with aplastic anemia(AA)and myelodysplastic syndrome(MDS). Blood 96:296a(abstract), 2000

• 9) Nomura S, Dan K, Hotta T et al:Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic throm-bocytopenic purpura. Blood 100:728-730, 2002

• 10) Kuter DJ:Biology and chemistry of thrombopoietic agents. Semin Hematol 47:243-248, 2010
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• 11) Thrombopoiesis and Thrombopoietins:Molecular, Cellular, Preclinical, and Clinical Biology, ed by Kuter DJ, Hunt P, Sheridan W et al, Humana Press, New Jersey, 1997

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• 14) Ishibashi T, Kimura H, Uchida T et al:Human inter-leukin 6 is a direct promoter of maturation of mega-karyocytes in vitro. Proc Natl Acad Sci USA 86:5953-5957, 1989

• 15) Asano S, Okano A, Ozawa K et al:In vivo effects of recombinant human interleukin-6 in primates:stimu-lated production of platelets. Blood 75:1602-1605, 1990

• 16) Teramura M, Kobayashi S, Hoshino S et al:Interleu-kin-11 enhances human megakaryocytopoiesis in vitro. Blood 79:327-331, 1992

• 17) Kawakita M, Ogawa M, Goldwasser E et al:Charac-terization of human megakaryocyte colony-stimulat-ing factor in the urinary extracts from patients with aplastic anemia and idiopathic thrombocytopenic purpura. Blood 61:556-560, 1983

• 18) Miura M, Jackson CW, Lyles SA:Increases in circu-lating megakaryocyte growth-promoting activity in the plasma of rats following whole body irradiation. Blood 63:1060-1066, 1984

• 19) Miyazaki H, Tamura S, Sudo T et al:Production and characterization of monoclonal antibodies against rat platelet GPIIb/IIIa. Thromb Res 59:941-953, 1990
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• 20) Miyazaki H, Inoue H, Yanagida M et al:Purification of rat megakaryocyte colony-forming cells using a monoclonal antibody against rat platelet glycoprotein IIb/IIIa. Exp Hematol 20:855-861, 1992
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• 21) Miyazaki H, Horie K, Shimada Y et al:A simple and quantitative liquid culture system to measure mega-karyocyte growth using highly purified CFU-MK. Exp Hematol 23:1224-1228, 1995

• 22) Shimada Y, Kato T, Ogami K et al:Production of thrombopoietin(TPO)by rat hepatocytes and hepa-toma cell lines. Exp Hematol 23:1388-1396, 1995

• 23) Ogami K, Shimada Y, Sohma Y et al:The sequence of a rat cDNA encoding thrombopoietin. Gene 158:309-310, 1995
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• 24) Vigon I, Mornon JP, Cocault L et al:Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene:identification of a member of the hematopoietic growth factor receptor superfamily. Proc Natl Acad Sci USA 89:5640-5644, 1992

• 25) Wendling F, Maraskovsky E, Debili N et al:cMpl ligand is a humoral regulator of megakaryocytopoie-sis. Nature 369:571-574, 1994

• 26) Feese MD, Tamada T, Kato Y et al:Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment. Proc Natl Acad Sci USA 101:1816-1821, 2004
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• 27) Nomura S, Ogami K, Kawamura K et al:Cellular localization of thrombopoietin mRNA in the liver by in situ hybridization. Exp Hematol 25:565-572, 1997
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• 28) Kato T, Horie K, Hagiwara T et al:GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin(TPO). Exp Hematol 24:1209-1214, 1996
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• 29) Horie K, Miyazaki H, Hagiwara T et al:Action of thrombopoietin at the megakaryocyte progenitor level is critical for the subsequent proplatelet production. Exp Hematol 25:169-176, 1997(Erratum in:Exp Hematol 25:270, 1997)

• 30) Matsumura I, Kanakura Y:Molecular control of megakaryopoiesis and thrombopoiesis. Int J Hematol 75:473-483, 2002
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• 31) Matsumura I, Kanakura Y, Kato T et al:The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells. Blood 88:3074-3082, 1996
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• 32) Oda A, Miyakawa Y, Druker BJ et al:Thrombopoietin-induced signal transduction and potentiation of platelet activation. Thromb Haemost 82:377-384, 1999
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• 33) Kobayashi M, Laver JH, Kato T et al:Thrombopoietin supports proliferation of human primitive hematopoietic cells in synergy with steel factor and/or interleukin-3. Blood 88:429-436, 1996
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• 34) Yoshihara H, Arai F, Hosokawa K et al:Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 1:685-697, 2007
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• 35) Shibuya K, Akahori H, Takahashi K et al:Multilin-eage hematopoietic recovery by a single injection of pegylated recombinant human megakaryocyte growth and development factor in myelosuppressed mice. Blood 91:37-45, 1998

執筆者一覧

P.40 掲載の参考文献

• 1) Kuter DJ, Begley CG:Recombinant human thrombo-poietin:basic biology and evaluation of clinical stud-ies. Blood 100:3457-3469, 2002

• 2) Basser RL, Rasko JE, Clarke K et al:Thrombopoietic effects of pegylated recombinant human megakaryo-cyte growth and development factor(PEG-rHuMGDF)in patients with advanced cancer. Lancet 348:1279-1281, 1996

• 3) Vadhan-Raj S, Murray LJ, Bueso-Ramos C et al:Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoi-etin in patients with cancer. Ann Intern Med 126:673-681, 1997

• 4) Basser RL, Rasko JE, Clarke K et al:Randomized, blinded, placebo-controlled phase I trial of pegylated recombinant human megakaryocyte growth and development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer. Blood 89:3118-3128, 1997
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• 5) Fanucchi M, Glaspy J, Crawford J et al:Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer. N Engl J Med 336:404-409, 1997
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• 6) Basser RL, Underhill C, Davis I et al:Enhancement of platelet recovery after myelosuppressive chemotherapy by recombinant human megakaryocyte growth and development factor in patients with advanced cancer. J Clin Oncol 18:2852-2861, 2000

• 7) Vadhan-Raj S, Verschraegen CF, Bueso-Ramos C et al:Recombinant human thrombopoietin attenuates carboplatin-induced severe thrombocytopenia and the need for platelet transfusions in patients with gynecologic cancer. Ann Intern Med 132:364-368, 2000
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• 8) Vadhan-Raj S, Patel S, Bueso-Ramos C et al:Importance of predosing of recombinant human thrombopoietin to reduce chemotherapy-induced early thrombocytopenia. J Clin Oncol 21:3158-3167, 2003
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• 9) Archimbaud E, Ottmann OG, Yin JA et al:A randomized, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor(PEG-rHuMGDF)as an adjunct to chemotherapy for adults with de novo acute myeloid leukemia. Blood 94:3694-3701, 1999
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• 10) Schiffer CA, Miller K, Larson RA et al:A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia, Blood 95:2530-2535, 2000
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• 11) Geissler K, Yin JA, Ganser A et al:Prior and concurrent administration of recombinant human mega-karyocyte growth and development factor in patients receiving consolidation chemotherapy for de novo acute myeloid leukemia--a randomized, placebo-controlled, double-blind safety and efficacy study. Ann Hematol 82:677-683, 2003

• 12) Usuki K, Tahara T, Iki S et al:Serum thrombopoietin level in various hematological diseases. Stem Cells 14:558-565, 1996
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• 13) Kuter DJ:What is the potential for thrombopoietic agents in acute leukemia? Best Pract Res Clin Haematol 24:553-558, 2011
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• 14) Nash RA, Kurzrock R, DiPersio J et al:A phase I trial of recombinant human thrombopoietin in patients with delayed platelet recovery after hemato-poietic stem cell transplantation. Biol Blood Marrow Transplant 6:25-34, 2000

• 15) Wolff SN, Herzig R, Lynch J et al:Recombinant human thrombopoietin(rhTPO)after autologous bone marrow transplantation:a phase I pharmacokinetic and pharmacodynamic study. Bone Marrow Trans-plant 27:261-268, 2001

• 16) Bolwell B, Vredenburgh J, Overmoyer B et al:Phase 1 study of pegylated recombinant human megakaryo-cyte growth and development factor(PEG-rHuMGDF)in breast cancer patients after autologous peripheral blood progenitor cell(PBPC)transplanta-tion. Bone Marrow Transplant 26:141-145, 2000

• 17) Fields KK, Crump M, Bence-Bruckler I et al:Use of PEG-rHuMGDF in platelet engraftment after autolo-gous stem cell transplantation. Bone Marrow Transplant 26:1083-1088, 2000

• 18) Schuster MW, Beveridge R, Frei-Lahr D et al:The effects of pegylated recombinant human megakaryo-cyte growth and development factor(PEG-rHuMGDF)on platelet recovery in breast cancer patients undergoing autologous bone marrow trans-plantation. Exp Hematol 30:1044-1050, 2002

• 19) Somlo G, Sniecinski I, ter Veer A et al:Recombinant human thrombopoietin in combination with granulo-cyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases periph-eral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemo-therapy, Blood 93:2798-2806, 1999

• 20) Gajewski JL, Rondon G, Donato ML et al:Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor for periph-eral blood progenitor cell mobilization. Biol Blood Marrow Transplant 8:550-556, 2002

• 21) Linker C, Anderlini P, Herzig R et al:Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous trans-plantation. Biol Blood Marrow Transplant 9:405-413, 2003

• 22) Kizaki M, Miyakawa Y, Ikeda Y:Long-term administration of pegylated recombinant human megakaryocyte growth and development factor dramatically improved cytopenias in a patient with myelodysplastic syndrome. Br J Haematol 122:764-767, 2003

• 23) Matsuda A, Misumi M, Ishikawa M et al:Long-term improvement of anaemia in a patient with aplastic anaemia by short-term administration of pegylated recombinant human megakaryocyte growth and development factor. Br J Haematol 125:818-819, 2004

• 24) Yonemura Y, Miyake H, Asou N et al:Long-term efficacy of pegylated recombinant human megakaryocyte growth and development factor in therapy of aplastic anemia. Int J Hematol 82:307-309, 2005
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• 25) Luo SS, Ogata K, Yokose N et al:Effect of thrombopoietin on proliferation of blasts from patients with myelodysplastic syndromes. Stem Cells 18:112-119, 2000
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• 26) Kuter DJ, Goodnough LT, Romo J et al:Thrombopoietin therapy increases platelet yields in healthy platelet donors. Blood 98:1339-1345, 2001
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• 27) Goodnough LT, Kuter DJ, McCullough J et al:Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin. Blood 98:1346-1351, 2001
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• 28) Nomura S, Dan K, Hotta T et al:Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura. Blood 100:728-730, 2002
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• 29) Li J, Yang C, Xia Y et al:Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98:3241-3248, 2001

• 30) Basser RL, O'Flaherty E, Green M et al:Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 99:2599-2602, 2002
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P.51 掲載の参考文献

• 1) Kaushansky K, Lok S, Holly RD et al:Promotion of megakaryocyte progenitor expansion and differentia-tion by the c-Mpl ligand thrombopoietin. Nature 369:568-571, 1994

• 2) de Sauvage FJ, Hass PE, Spencer SD et al:Stimula-tion of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 369:533-538, 1994

• 3) Kuter DJ, Beeler DL, Rosenberg RD:The purification of megapoietin:a physiological regulator of mega-karyocyte growth and platelet production. Proc Natl Acad Sci USA 91:11104-11108, 1994

• 4) Bartley TD, Bogenberger J, Hunt P et al:Identifica-tion and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 77:1117-1124, 1994

• 5) Kato T, Ogami K, Shimada Y et al:Purification and characterization of thrombopoietin. J Biochem 118:229-236, 1995
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• 6) Cwirla SE, Balasubramanian P, Duffin DJ et al:Pep-tide agonist of the thrombopoietin receptor as potent as the natural cytokine. Science 276:1696-1699, 1997

• 7) Kuter DJ:Biology and chemistry of thrombopoietic agents. Semin Hematol 47:243-248, 2010
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• 8) 医薬品インタビューフォーム ロミプレート(R)皮下注250μg調整用(第1版)[http://www.info.pmda.go.jp/go/pack/3999430D1024_1_02/]

• 9) Kumagai Y, Fujita T, Ozaki M et al:Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects:a randomized, placebo-controlled study. J Clin Pharmacol 47:1489-1497, 2007
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• 10) Shirasugi Y, Ando K, Hashino S et al:A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura. Int J Hematol 90:157-165, 2009
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• 11) Shirasugi Y, Ando K, Miyazaki K 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 94:71-80, 2011
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• 12) Shirasugi Y, Ando K, Miyazaki K et al:An open-label extension study evaluating the safety and efficacy of romiplostim for up to 3.5 years in thrombocytopenic Japanese patients with immune thrombocytopenic purpura(ITP). Int J Hematol 95:652-659, 2012
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• 13) Wang B, Nichol JL, Sullivan JT:Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 76:628-638, 2004
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• 14) Bussel JB, Kuter DJ, George JN et al:AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 355:1672-1681, 2006
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• 15) Newland A, Caulier MT, Kappers-Klunne M 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 135:547-553, 2006
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• 16) Kuter DJ, Bussel JB, Lyons RM et al:Efficacy of romiplostim in patients with chronic immune throm-bocytopenic purpura:a double-blind randomised controlled trial. Lancet 371:395-403, 2008

• 17) George JN, Mathias SD, Go RS et al:Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura:results from two randomized, placebo-controlled trials. Br J Haematol 144:409-415, 2009
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• 18) Bussel JB, Kuter DJ, Pullarkat V et al:Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 113:2161-2171, 2009
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• 20) Kuter DJ, Mufti GJ, Bain BJ et al:Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 114:3748-3756, 2009
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• 21) Kutcr DJ, Rummel M, Boccia R et al:Romiplostim or standard of care in patients with immune thrombocy-topenia. N Engl J Med 363:1889-1899, 2010

P.59 掲載の参考文献

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• 2) Mukai HY, Kojima H, Todokoro K et al:Serum thrombopoietin(TPO)levels in patients with amega-karyocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost 76:675-678, 1996

• 3) Nomura S, Dan K, Hotta T et al:Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic throm-bocytopenic purpura. Blood 100:728-730, 2002

• 4) Li J, Yang C, Xia Y et al:Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98:3241-3248, 2001

• 5) Kuter DJ:New thrombopoietic growth factors. Blood 109:4607-4616, 2007
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• 6) Erickson-Miller CL, Delorme E, Tian SS et al:Pre-clinical activity of eltrombopag(SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells 27:424-430, 2009

• 7) Nurden AT, Viallard JF, Nurden P:New-generation drugs that stimulate platelet production in chronic immune thrombocytopenic purpura. Lancet 373:1562-1569, 2009
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• 8) Bussel JB, Cheng G, Saleh MN et al:Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 357:2237-2247, 2007
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• 9) Bussel JB, Provan D, Shamsi T et al:Effect of eltrom-bopag on platelet counts and bleeding during treat-ment of chronic idiopathic thrombocytopenic pur-pura:a randomised, double-blind, placebo-controlled trial. Lancet 373:641-648, 2009

• 10) Tomiyama Y, Miyakawa Y, Okamoto S et al:A lower starting dose of eltrombopag is efficacious in Japa-nese patients with previously treated chronic immune thrombocytopenia. J Thromb Haemost 10:799-806, 2012

• 11) 藤村欣吾, 宮川義隆, 倉田義之ほか:成人特発性血小板減少性紫斑病治療の参照ガイド2012年版, 臨床血液 53:433-442, 2012

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• 15) Erhardt JA, Erickson-Miller CL, Aivado M et al:Comparative analyses of the small molecule thrombo-poietin receptor agonist eltrombopag and thrombo-poietin on in vitro platelet function. Exp Hematol 37:1030-1037, 2009

• 16) Psaila B, Bussel JB, Linden MD et al:In vivo effects of eltrombopag on platelet function in immune throm-bocytopenia:no evidence of platelet activation. Blood 119:4066-4072, 2012

• 17) Bao W, Bussel JB, Heck S et al:Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood 116:4639-4645, 2010
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• 18) Fujita S, Nakanishi T, Yoshimura H et al:TGF-β1 and sCTLA-4 levels are increased in eltrombopag-exposed patients with ITP. Thromb Res 130:415-419, 2012

• 19) Maruyama T, Li J, Vaque JP et al:Control of the dif-ferentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3. Nat Immunol 12:86-95, 2011

目次

P.73 掲載の参考文献

• 1) Nurden AT, Viallard JF, Nurden P:New-generation drugs that stimulate platelet production in chronic immune thrombocytopenic purpura. Lancet 373:1562-1569, 2009
  pubmed

• 2) Kuter DJ, Begley CG:Recombinant human thrombo-poietin:basic biology and evaluation of clinical stud-ies. Blood 100:3457-3469, 2002

• 3) Kuter DJ:New thrombopoietic growth factors. Blood 109:4607-4616, 2007
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• 4) Kuter DJ, Bussel JB, Lyons RM et al:Efficacy of romiplostim in patients with chronic immune throm-bocytopenic purpura:a double-blind randomised controlled trial. Lancet 371:395-403, 2008

• 5) Cheng G, Saleh MN, Marcher C et al:Eltrombopag for management of chronic immune thrombocytopenia(RAISE):a 6-month, randomised, phase 3 study. Lancet 377:393-402, 2011

• 6) Nieto M, Calvo G, Hudson I et al:The European Medicines Agency review of eltrombopag(Revolade)for the treatment of adult chronic immune(idiopathic)thrombocytopenic purpura:summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Haematologica 96:e33-e40, 2011

• 7) ロミプレート(R)皮下注250μg調製用添付文書

• 8) Kurata Y, Hayashi S, Kiyoi T et al:Diagnostic value of tests for reticulated platelets, plasma glycocalicin, and thrombopoietin levels for discriminating between hyperdestructive and hypoplastic thrombocytopenia. Am J Clin Pathol 115:656-664, 2001
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• 9) 林悟, 西山美保, 末久悦次ほか:網状血小板測定法2法の比較検討と臨床的有用性の検討:フローサイトメトリー(FCM)法と多項目自動血球分析装置 XE-2100による自動測定(IPF)法. 臨床病理 57:1039-1044, 2009
  Medical*Online

• 10) Aledort LM, Hayward CP, Chen MG et al:Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies. Am J Hematol 76:205-213, 2004
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• 11) Gernsheimer TB, George JN, Aledort LM et al:Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia(ITP). J Thromb Haemost 8:1372-1382, 2010
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• 12) Bussel JB, Kuter DJ, Pullarkat V et al:Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 113:2161-2171, 2009
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• 13) レボレード(R)錠を正しくご使用いただくために:適正使用ガイド, (池田康夫, 金倉譲総監修)2011年12月

• 14) Tomiyama Y, Miyakawa Y, Okamoto S et al:A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J Thromb Haemost 10:799-806, 2012
  pubmed

• 15) レボレード(R)錠の適正使用に関するお願い～血栓塞栓症について～, 2012年7月

• 16) Kuter DJ, Mufti GJ, Bain BJ et al:Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 114:3748-3756, 2009
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• 17) Mufti G, Bagg A, Hasserjian R et al:Bone marrow reticulin in patients with immune thrombocytopenic purpura. Blood 108:3982(abstract), 2006

• 18) Giagounidis A, Mufti GJ, Kantarjian HM et al:Treatment with the thrombopoietin(TPO)-receptor agonist romiplostim in thrombocytopenic patients(Pts)with low or intermediate-1(Int-1)risk myelodysplastic syndrome(MDS):results of a randomized, double-blind, placebo(PBO)-controlled study[abstract]. Blood 118:117, 2011

• 19) Olnes MJ, Scheinberg P, Calvo KR et al:Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 367:11-19, 2012
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• 20) Bussel JB, Kuter DJ, George JN et al:AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 355:1672-1681, 2006
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• 21) Li J, Yang C, Xia Y et al:Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98:3241-3248, 2001

• 22) Molineux G:The development of romiplostim for patients with immune thrombocytopenia. Ann NY Acad Sci 1222:55-63, 2011
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• 23) Jawa V, Hokom M, Hu Z et al:Assessment of immunogenicity of romiplostim in clinical studies with ITP subjects. Ann Hematol 89(suppl 1):S75-S85, 2010

• 24) Bussel JB, Buchanan GR, Nugent DJ et al:A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood 118:28-36, 2011
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Part 1 血小板産生機構とトロンボポエチンの基礎をみる

P.85 掲載の参考文献

• 1) 倉田義之:臨床調査個人票(平成21年度)集計による特発性血小板減少性紫斑病の全国疫学調査厚生労働科学研究費補助金 難治性疾患克服研究事業「血液凝固異常症に関する調査研究」平成23年度総括・分担研究報告書(研究代表者 村田満). 62-73, 平成24年3月

• 2) McMillan R, Tani P, Millard F et al:Platelet-associ-ated and plasma anti-glycoprotein autoantibodies in chronic ITP. Blood 70:1040-1045, 1978

• 3) Heyns AP, Badenhorst PN, Lotter MG et al:Platelet turnover and kinetics in immune thrombocytopenic purpura:results with autologous 111In-labeled plate-let and homologous 51Cr-labeled platelet differ. Blood 67:86-92, 1986

• 4) Chang M, Nakagawa PA, Williams SA et al:Immune thrombocytopenic purpura(ITP)plasma and purified ITP monoclonal autoantibodies inhibit megakaryocy-topoiesis in vitro. Blood 102:887-895, 2003

• 5) McMillan R, Wang L, Tomer A et al:Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 103:1364-1369, 2004
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• 6) Nugent D, McMillan R, Nichol JL et al:Pathogenesis of chronic immune thrombocytopenia:increased platelet destruction and/or decreased platelet pro-duction. Br J Haematol 146:585-596, 2009
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• 7) Emmons RV, Reid DM, Cohen RL et al:Human thrombopoietin levels are high when thrombocytope-nia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood 87:4068-4071, 1996

• 8) George JN, Woolf SH, Raskob GE et al:Idiopathic thrombocytopenic purpura:a practice guideline developed by explicit methods for the American Soci-ety of Hematology. Blood 88:3-40, 1996

• 9) British Committee for Standards in Haematology Gen-eral Haematology Task Force:Guidelines for the investigation and management of idiopathic thrombo-cytopenic purpura in adults, children and in preg-nancy. Br J Haematol 120:574-596, 2003

• 10) Provan D, Stasi R, Newland AC et al:International consensus report on the investigation and manage-ment of primary immune thrombocytopenia. Blood 115:168-186, 2010

• 11) Neunert C, Lim W, Crowther M et al:The American Society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190-4207, 2011
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• 12) 藤村欣吾, 宮川義隆, 倉田義之ほか:成人特発性血小板減少性紫斑病治療の参照ガイド2012年版, 臨床血液 53:433-442, 2012

• 13) Nomura S, Dan K, Hotta T et al:Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic throm-bocytopenic purpura. Blood 100:728-730, 2002

• 14) Kuter DJ, Bussel JB, Lyons RM et al:Efficacy of romiplostim in patients with chronic immune throm-bocytopenic purpura:a double-blind randomized controlled trial. Lancet 371:395-403, 2008

• 15) Bussel JB, Cheng G, Saleh MN et al:Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 357:2237-2247, 2007
  pubmed

• 16) Cheng G, Saleh MN, Marcher C et al:Eltrombopag for management of chronic immune thrombocytopenia(RAISE):a 6-month, randomized, phase 3 study. Lancet 377:393-402, 2011

• 17) Kuter DJ, Rummel M, Boccia R et al:Romiplostim or standard of care in patients with immune thrombocy-topenia. N Engl J Med 363:1889-1899, 2010
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• 18) Shirasugi Y, Ando K, Miyazaki K et al:An open-label extension study evaluating the safety and efficacy of romiplostim for up to 3.5 years in thrombocytopenic Japanese patients with immune thrombocytopenic purpura(ITP). Int J Hematol 95:652-659, 2012
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• 19) Fujimura K, Kuwana M, Kurata Y et al:Is eradication therapy useful as the first line of treatment in Helicobacter pylori-positive idiopathic thrombocytopenic purpura? Analysis of 207 eradicated chronic ITP cases in Japan. Int J Hematol 81:162-168, 2005
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Part 2 トロンボポエチン受容体作動薬の基礎と臨床をみる

P.98 掲載の参考文献

• 1) 宮川義隆:ITPの新しい治療薬. 血栓止血誌 21:262-270, 2010

• 2) 宮川義隆:特発性血小板減少性紫斑病の新しい治療薬. 血液フロンティア 21:83-94, 2011

• 3) Homeida S, Ebdon C, Batty P et al:New thrombopoi-etin receptor agonists for platelet disorders. Drugs of Today 48:293-301, 2012

• 4) McHutchison JG, Dusheiko G, Shiffman ML et al:Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 357:2227-2236, 2007
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• 5) Afdhal N, Dusheiko G, Giannini E et al:Final results of ENABLE-1, a phase 3, multicenter study of eltrombopag as an adjunct for antiviral treatment of hepatitis C virus-related chronic liver disease associ-ated with thrombocytopenia. 62th annual meeting of the American association for the study of liver dis-ease. abstract, 2011[http://www.natap.org/2011/AASLD/AASLD_110.htm]

• 6) Dusheiko G, Afdhal N, Giannini E et al:Results of ENABLE-2, a phase 3, placebo-controlled, multi-center study of eltrombopag, pegintereferon alpha-2b, and ribavirin treatment in patients with hepatitis C and thrombocytopenia. 47th annual meeting of European association for the study of the liver dis-ease. abstract, 2012[http://www.natap.org/2012/EASL/EASL_97.htm]

• 7) Kawaguchi T, Komori A, Seike M et al:Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia:a ran-domized, open-label, phase II study. J Gastroenterol:(epub ahead of print), 2012

• 8) Afdhal N, Giannini E, Tayyab GN et al:1185 Eltrom-bopag in chronic liver disease patients with thrombo-cytopenia undergoing an elective invasive proce-dures:results from elevate, a randomized clinical trial. J Hepatol 52(Suppl 1):S460, abstract, 2010

• 9) Clinical study report for study TPL 104054, a randomised double-blind, placebo-controlled, multicenter study to evaluate the safety and efficacy of eltrombopag to reduce the need for platelet transfusion in thrombocytopenic subjects with chronic liver disease undergoing elective invasive procedures. ELEVATE:eltrombopag evaluated for its ability to overcome thrombocytopenia and enable procedures. [http://www.gsk-clinicalstudyregister.com/result_comp_list.jsp?compound=eltrombopag&studyType=All&phase=All&population=All&marketing=All]

• 10) Olnes MJ, Scheinberg P, Calvo KR et al:Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 367:11-19, 2012
  pubmed

• 11) Kantarjian H, Fenaux P, Sekeres MA et al:Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol 28:437-444, 2010
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• 12) Giagounidis A, Mufti GJ, Kantarjia HM et al:Treatment with the thrombopoietin(TPO)-receptor agonist romiplostim in thrombocytopenic patients(Pts)with low or intermediate-1(Int-1)risk myelodysplastic syndrome(MDS):results of a randomized, double-blind, placebo(PBO)-controlled study. ASH Annual Meeting Abstracts 118:117, 2011

• 13) Kantarjian HM, Giles FJ, Greenberg PL et al:Phase 2 study of romiplostim in patients with low-or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood 116:3163-3170, 2010
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• 14) Kellum A, Jagiello-Gruszfeld A, Bondarenko IN et al:A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safetyof eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors. Curr Med Res Opin 26:2339-2346, 2010

• 15) Nakamura T, Miyakawa Y, Miyamura A et al:A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. Blood 107:4300-4307, 2006

• 16) Yamane A, Nakamura T, Suzuki H et al:Interferon-alpha 2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes. Blood 112:542-550, 2008

• 17) Nogami W, Yoshida H, Koizumi K et al:The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoie-sis. Haematologica 93:1495-1504, 2008

• 18) Roth M, Will B, Simkin G et al:Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood 120:386-394, 2012
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Part 3 トロンボポエチン受容体作動薬の安全性と副作用をみる - 副作用の頻度とその対策 -

P.105 掲載の参考文献

• 1) 藤村欣吾, 宮川義隆, 倉田義之ほか:成人特発性血小板減少性紫斑病治療の参照ガイド2012年版. 臨床血液 53:433-442, 2012

P.108 掲載の参考文献

• 1) Neunert C, Lim W, Crowther M et al:The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190-4207, 2011
  pubmed

• 2) Bussel JB, Buchanan GR, Nugent DJ et al:A random-ized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood 118:28-36, 2011

• 3) Klaassen RJ, Mathias SD, Buchanan G et al:Pilot study of the effect of romiplostim on child health-related quality of life(HRQoL)and parental burden in immune thrombocytopenia(ITP). Pediatr Blood Cancer 58:395-398, 2012
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• 4) Bussel J, Grainger J, Despotovic J et al:Eltrombopag for the treatment of childhood chronic ITP:the PETIT study, a placebo-controlled clinical trial. Hae-matologica 97(suppl 1):201-202, 2012

P.109 掲載の参考文献

• 1) Neunert C, Lim W, Crowther M et al:The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190-4207, 2011
  pubmed

• 2) Provan D, Stasi R, Newland AC et al:International Consensus Report on the investigation and manage-ment of primary immune thrombocytopenia. Blood 115:168-186, 2010

• 3) ロミプレート(R)皮下注250μg調製用, 添付文書[2011年4月作成(第1版)]

• 4) レボレード(R)錠12.5mg・25mg, 添付文書[2010年10月作成(第1版)]

P.110 掲載の参考文献

• 1) ITP治療の参照ガイド作成委員会:成人特発性血小板減少性紫斑病治療の参照ガイド2012年版. 臨床血液 53:433-442, 2012

• 2) Neunert C, Lim W, Crowther M et al:The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190-4207, 2011
  pubmed

• 3) Stasi R, Newland A, Thornton P et al:Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate. Ann Hematol 89:1185-1195, 2010
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• 4) Kuter DJ, Phil D, Rummel A et al:Romiplostim or standard of care in patients with immune thrombocy-topenia. N Engl J Med 363:1889-1899, 2010

• 5) Ghanima W, Godeau B, Cines DB et al:How I treat immune thrombocytopenia(ITP):the choice between splenectomy or a medical therapy as a second-line treatment. Blood 120:960-969, 2012
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