Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Clinical applications of thrombopoietic growth factors

David J Kuter, MD, DPhil
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


The use of hematopoietic growth factors has markedly changed the practice of medicine. Erythroid growth factors (eg, erythropoietin, darbepoetin) and myeloid growth factors (eg, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor) have allowed the specific stimulation of the production of erythrocytes and neutrophils, respectively. (See "Introduction to recombinant hematopoietic growth factors".)

With the discovery of thrombopoietin (TPO) and the development of a variety of peptide and non-peptide TPO receptor agonists, clinically effective thrombopoietic growth factors have now entered the clinical armamentarium. This topic review will discuss the thrombopoietins and TPO receptor agonists that have been developed, their activity in preclinical models, and the available clinical studies. The biology of TPO is discussed separately. (See "Biology and physiology of thrombopoietin".)


The potential clinical applications of thrombopoietic growth factors are suggested by analyzing the use of platelet transfusions (figure 1). (See "Clinical and laboratory aspects of platelet transfusion therapy", section on 'Indications for platelet transfusion'.)

Two TPO receptor agonists (romiplostim, eltrombopag) have been approved for the treatment of chronic immune thrombocytopenia (chronic ITP). (See "Immune thrombocytopenia (ITP) in adults: Second-line and subsequent therapies", section on 'Thrombopoietin receptor agonists'.)

One thrombopoietic growth factor (eltrombopag) has been approved for the treatment of thrombocytopenia in patients with hepatitis C who are being treated with interferon (see "Management of the side effects of peginterferon and ribavirin used for treatment of chronic hepatitis C virus infection", section on 'Thrombocytopenia') and for the treatment of aplastic anemia. (See "Treatment of aplastic anemia in adults", section on 'Eltrombopag'.)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 06, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol 2013; 98:10.
  2. Kuter DJ. Milestones in understanding platelet production: a historical overview. Br J Haematol 2014; 165:248.
  3. Sheridan WP, Kuter DJ. Mechanism of action and clinical trials of Mpl ligand. Curr Opin Hematol 1997; 4:312.
  4. Kuter DJ. New thrombopoietic growth factors. Clin Lymphoma Myeloma 2009; 9 Suppl 3:S347.
  5. Kuter DJ. New thrombopoietic growth factors. Blood 2007; 109:4607.
  6. Katsube T, Ishibashi T, Kano T, Wajima T. Population Pharmacokinetic and Pharmacodynamic Modeling of Lusutrombopag, a Newly Developed Oral Thrombopoietin Receptor Agonist, in Healthy Subjects. Clin Pharmacokinet 2016; 55:1423.
  7. Kim ES. Lusutrombopag: First Global Approval. Drugs 2016; 76:155.
  8. Kuter DJ. Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med 2009; 60:193.
  9. Vadhan-Raj S, Murray LJ, Bueso-Ramos C, et al. Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Ann Intern Med 1997; 126:673.
  10. Basser RL, Begley CG. Thrombopoietin. Cancer Invest 2001; 19:660.
  11. Cwirla SE, Balasubramanian P, Duffin DJ, et al. Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine. Science 1997; 276:1696.
  12. Molineux G. The development of romiplostim for patients with immune thrombocytopenia. Ann N Y Acad Sci 2011; 1222:55.
  13. Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 2004; 76:628.
  14. Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine 2004; 25:52.
  15. Bussel JB, Kuter DJ, George JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 2006; 355:1672.
  16. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008; 371:395.
  17. Kuter DJ, Rummel M, Boccia R, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med 2010; 363:1889.
  18. Kuter DJ, Bussel JB, Newland A, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol 2013; 161:411.
  19. Sekeres MA, Kantarjian H, Fenaux P, et al. Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes. Cancer 2011; 117:992.
  20. 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 2010; 28:437.
  21. 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 2010; 116:3163.
  22. Duffy KJ, Shaw AN, Delorme E, et al. Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics. J Med Chem 2002; 45:3573.
  23. Duffy KJ, Darcy MG, Delorme E, et al. Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis. J Med Chem 2001; 44:3730.
  24. Duffy KJ, Price AT, Delorme E, et al. Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 2. Rational design of naphtho[1,2-d]imidazole thrombopoietin mimics. J Med Chem 2002; 45:3576.
  25. Erickson-Miller CL, DeLorme E, Tian SS, et al. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol 2005; 33:85.
  26. Jenkins JM, Williams D, Deng Y, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007; 109:4739.
  27. Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373:641.
  28. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011; 377:393.
  29. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007; 357:2237.
  30. Saleh MN, Bussel JB, Cheng G, et al. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood 2013; 121:537.
  31. McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007; 357:2227.
  32. Desmond R, Townsley DM, Dumitriu B, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 2014; 123:1818.
  33. Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 2012; 367:11.
  34. Desjardins RE, Tempel DL, Lucek R, Kuter DJ. Single and multiple oral doses of AKR-501 (TM477) increase the platelet count in healthy volunteers (abstract). Blood 2006; 108:145a.
  35. Terrault NA, Hassanein T, Howell CD, et al. Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure. J Hepatol 2014; 61:1253.
  36. Bussel JB, Kuter DJ, Aledort LM, et al. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood 2014; 123:3887.
  37. Kaye JA. FDA Licensure of NEUMEGA to prevent severe chemotherapy-induced thrombocytopenia. In: Thrombopoietin: From Molecule to Medicine, Murphy MJ, Kuter DJ (Eds), AlphaMed Press, Miamisburg 1998. p.207.
  38. Teramura M, Kobayashi S, Yoshinaga K, et al. Effect of thrombopoietin (c-Mpl ligand) alone and in combination with other hematopoietic growth factors on human megakaryocytopoiesis in serum-free cultures. Int J Hematol 1997; 66:373.
  39. Teramura M, Kobayashi S, Yoshinaga K, et al. Effect of interleukin 11 on normal and pathological thrombopoiesis. Cancer Chemother Pharmacol 1996; 38 Suppl:S99.
  40. Robb L, Li R, Hartley L, et al. Infertility in female mice lacking the receptor for interleukin 11 is due to a defective uterine response to implantation. Nat Med 1998; 4:303.
  41. Nandurkar HH, Robb L, Tarlinton D, et al. Adult mice with targeted mutation of the interleukin-11 receptor (IL11Ra) display normal hematopoiesis. Blood 1997; 90:2148.
  42. Tsimberidou AM, Giles FJ, Khouri I, et al. Low-dose interleukin-11 in patients with bone marrow failure: update of the M. D. Anderson Cancer Center experience. Ann Oncol 2005; 16:139.
  43. Aribi A, Kantarjian H, Koller C, et al. The effect of interleukin 11 on thrombocytopenia associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 2008; 113:1338.
  44. Tepler I, Elias L, Smith JW 2nd, et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 1996; 87:3607.
  45. Isaacs C, Robert NJ, Bailey FA, et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol 1997; 15:3368.
  46. 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 2003; 122:764.
  47. Kuter DJ, Begley CG. Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. Blood 2002; 100:3457.
  48. Nichol JL. Thrombopoietin levels after chemotherapy and in naturally occurring human diseases. Curr Opin Hematol 1998; 5:203.
  49. Emmons RV, Reid DM, Cohen RL, et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood 1996; 87:4068.
  50. McMillan R, Wang L, Tomer A, et al. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004; 103:1364.
  51. Ballem PJ, Segal GM, Stratton JR, et al. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest 1987; 80:33.
  52. Rice L, Nichol JL, McMillan R, et al. Cyclic immune thrombocytopenia responsive to thrombopoietic growth factor therapy. Am J Hematol 2001; 68:210.
  53. 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 2002; 100:728.
  54. Kuter DJ, Bussel J, Newland A, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenic purpura (ITP): 3-year update from an open-label extension study. Blood 2008; 112:154a.
  55. Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009; 113:2161.
  56. Martin TG 3rd, Somberg KA, Meng YG, et al. Thrombopoietin levels in patients with cirrhosis before and after orthotopic liver transplantation. Ann Intern Med 1997; 127:285.
  57. Peck-Radosavljevic M, Wichlas M, Zacherl J, et al. Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production. Blood 2000; 95:795.
  58. Afdhal NH, Dusheiko GM, Giannini EG, et al. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 2014; 146:442.
  59. Afdhal NH, Giannini EG, Tayyab G, et al. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 2012; 367:716.
  60. Makar RS, Zhukov OS, Sahud MA, Kuter DJ. Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. Am J Hematol 2013; 88:1041.
  61. Townsley DM, Scheinberg P, Winkler T, et al. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med 2017; 376:1540.
  62. Will B, Kawahara M, Luciano JP, et al. Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood 2009; 114:3899.
  63. Komatsu N, Okamoto T, Yoshida T, et al. Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increased platelet counts (plt) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS) (abstract). Blood 2000; 96:296a.
  64. Giagounidis A, Mufti GJ, Fenaux P, 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; 120:1838.
  65. 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 2012; 120:386.
  66. Platzbecker U, Wong RS, Verma A, et al. Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial. Lancet Haematol 2015; 2:e417.
  67. Balduini CL, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol 2011; 154:161.
  68. Pecci A, Gresele P, Klersy C, et al. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood 2010; 116:5832.
  69. Harker LA, Carter RA, Marzec UM, et al. Correction of thrombocytopenia and ineffective platelet production in patients infected with human immunodeficiency virus (HIV) by PEG-rHuMGDF therapy (abstract). Blood 1998; 92:707a.
  70. Kuter DJ. Managing thrombocytopenia associated with cancer chemotherapy. Oncology (Williston Park) 2015; 29:282.
  71. Hokom MM, Lacey D, Kinstler OB, et al. Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice. Blood 1995; 86:4486.
  72. Columbyova L, Loda M, Scadden DT. Thrombopoietin receptor expression in human cancer cell lines and primary tissues. Cancer Res 1995; 55:3509.
  73. Erickson-Miller CL, Pillarisetti K, Kirchner J, et al. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors. BMC Cancer 2012; 12:405.
  74. 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 1997; 336:404.
  75. 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 1997; 89:3118.
  76. 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 2000; 132:364.
  77. Moskowitz CH, Hamlin PA, Gabrilove J, et al. Maintaining the dose intensity of ICE chemotherapy with a thrombopoietic agent, PEG-rHuMGDF, may confer a survival advantage in relapsed and refractory aggressive non-Hodgkin lymphoma. Ann Oncol 2007; 18:1842.
  78. Zhang X, Chuai Y, Nie W, et al. Thrombopoietin receptor agonists for prevention and treatment of chemotherapy-induced thrombocytopenia in patients with solid tumours. Cochrane Database Syst Rev 2017; 11:CD012035.
  79. Winer ES, Safran H, Karaszewska B, et al. Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study. Cancer Med 2015; 4:16.
  80. Parameswaran R, Lunning M, Mantha S, et al. Romiplostim for management of chemotherapy-induced thrombocytopenia. Support Care Cancer 2014; 22:1217.
  81. 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 2000; 95:2530.
  82. 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 1999; 94:3694.
  83. Kuter DJ. What is the potential for thrombopoietic agents in acute leukemia? Best Pract Res Clin Haematol 2011; 24:553.
  84. Kuter DJ. What is the role of novel thrombopoietic agents in the management of acute leukemia? Best Pract Res Clin Haematol 2016; 29:372.
  85. Geissler K, Yin JA, Ganser A, et al. Prior and concurrent administration of recombinant human megakaryocyte 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 2003; 82:677.
  86. Nash RA, Kurzrock R, DiPersio J, et al. A phase I trial of recombinant human thrombopoietin in patients with delayed platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2000; 6:25.
  87. Schuster MW, Beveridge R, Frei-Lahr D, et al. The effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet recovery in breast cancer patients undergoing autologous bone marrow transplantation. Exp Hematol 2002; 30:1044.
  88. Glaspy J, Vredenburgh J, Demetri GD, et al. Effects of PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) before high dose chemotherapy (HDC) with peripheral blood progenitor cell (PBPC) support (abstract). Blood 1997; 90:580a.
  89. Fibbe WE, Heemskerk DP, Laterveer L, et al. Accelerated reconstitution of platelets and erythrocytes after syngeneic transplantation of bone marrow cells derived from thrombopoietin pretreated donor mice. Blood 1995; 86:3308.
  90. Somlo G, Sniecinski I, ter Veer A, et al. Recombinant human thrombopoietin in combination with granulocyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy. Blood 1999; 93:2798.
  91. Marshall AL, Goodarzi K, Kuter DJ. Romiplostim in the management of the thrombocytopenic surgical patient. Transfusion 2015; 55:2505.
  92. Moussa MM, Mowafy N. Preoperative use of romiplostim in thrombocytopenic patients with chronic hepatitis C and liver cirrhosis. J Gastroenterol Hepatol 2013; 28:335.
  93. Kaushansky K. Thrombopoietin and the hematopoietic stem cell. Blood 1998; 92:1.
  94. Solar GP, Kerr WG, Zeigler FC, et al. Role of c-mpl in early hematopoiesis. Blood 1998; 92:4.
  95. Piacibello W, Sanavio F, Garetto L, et al. Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood. Blood 1997; 89:2644.
  96. Yagi M, Ritchie KA, Sitnicka E, et al. Sustained ex vivo expansion of hematopoietic stem cells mediated by thrombopoietin. Proc Natl Acad Sci U S A 1999; 96:8126.
  97. Thon JN, Italiano JE. Platelet formation. Semin Hematol 2010; 47:220.
  98. Choi ES, Nichol JL, Hokom MM, et al. Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood 1995; 85:402.
  99. Kuter DJ, Goodnough LT, Romo J, et al. Thrombopoietin therapy increases platelet yields in healthy platelet donors. Blood 2001; 98:1339.
  100. Goodnough LT, Kuter DJ, McCullough J, et al. Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin. Blood 2001; 98:1346.
  101. Vadhan-Raj S, Kavanagh JJ, Freedman RS, et al. Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study. Lancet 2002; 359:2145.
  102. Ballmaier M, Schulze H, Strauss G, et al. Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin. Blood 1997; 90:612.
  103. Ballmaier M, Germeshausen M, Schulze H, et al. c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood 2001; 97:139.
  104. van den Oudenrijn S, Bruin M, Folman CC, et al. Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia. Br J Haematol 2000; 110:441.
  105. Orita T, Tsunoda H, Yabuta N, et al. A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor. Blood 2005; 105:562.
  106. Kuter DJ. Thrombopoietin: biology, clinical applications, role in the donor setting. J Clin Apher 1996; 11:149.
  107. Li J, Yang C, Xia Y, et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001; 98:3241.
  108. 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 2002; 99:2599.
  109. Sarpatwari A, Bennett D, Logie JW, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica 2010; 95:1167.
  110. Severinsen MT, Engebjerg MC, Farkas DK, et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2011; 152:360.
  111. Harker LA, Marzec UM, Hunt P, et al. Dose-response effects of pegylated human megakaryocyte growth and development factor on platelet production and function in nonhuman primates. Blood 1996; 88:511.
  112. Harker LA, Hunt P, Marzec UM, et al. Regulation of platelet production and function by megakaryocyte growth and development factor in nonhuman primates. Blood 1996; 87:1833.
  113. Harker LA. Platelets in thrombotic disorders: quantitative and qualitative platelet disorders predisposing to arterial thrombosis. Semin Hematol 1998; 35:241.
  114. Fontana V, Jy W, Ahn ER, et al. Increased procoagulant cell-derived microparticles (C-MP) in splenectomized patients with ITP. Thromb Res 2008; 122:599.
  115. Yan XQ, Lacey D, Fletcher F, et al. Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice. Blood 1995; 86:4025.
  116. Frey BM, Rafii S, Teterson M, et al. Adenovector-mediated expression of human thrombopoietin cDNA in immune-compromised mice: insights into the pathophysiology of osteomyelofibrosis. J Immunol 1998; 160:691.
  117. Villeval JL, Cohen-Solal K, Tulliez M, et al. High thrombopoietin production by hematopoietic cells induces a fatal myeloproliferative syndrome in mice. Blood 1997; 90:4369.
  118. Yanagida M, Ide Y, Imai A, et al. The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats. Br J Haematol 1997; 99:739.
  119. Ulich TR, del Castillo J, Senaldi G, et al. Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice. Blood 1996; 87:5006.
  120. Douglas VK, Tallman MS, Cripe LD, Peterson LC. Thrombopoietin administered during induction chemotherapy to patients with acute myeloid leukemia induces transient morphologic changes that may resemble chronic myeloproliferative disorders. Am J Clin Pathol 2002; 117:844.
  121. Kuter DJ, Mufti GJ, Bain BJ, et al. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 2009; 114:3748.
  122. Kuter DJ, Bain B, Mufti G, et al. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007; 139:351.
  123. Janssens A, Rodeghiero F, Anderson D, et al. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Ann Hematol 2016; 95:1077.
  124. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022291s014lbl.pdf (Accessed on August 29, 2016).
Topic Outline