• 四川大學(xué)華西醫(yī)院血液科血液學(xué)研究室（成都，610041）;

原發(fā)免疫性血小板減少癥（ITP）是一種常見的出血性疾病，其發(fā)病機(jī)制仍不十分清楚?，F(xiàn)有治療方案在ITP的治療中取得一定的療效，如糖皮質(zhì)激素、靜脈注射免疫球蛋白以及脾切除等，但仍有較多患者面臨復(fù)發(fā)難治的問題?，F(xiàn)將近年ITP發(fā)病機(jī)制、診斷和治療等方面的研究進(jìn)展作一綜述。

引用本文： 李艷秋,牛挺. 原發(fā)免疫性血小板減少癥研究進(jìn)展. 華西醫(yī)學(xué), 2012, 27(10): 1570-1574. doi: 復(fù)制

1. 　Watson-Williams EJ, Macpherson AI, Davidson S. The treatment of idiopathic thrombocytopenic purpura: a review of ninety-three cases[J]. Lancet, 1958, 2(7040): 221-226.
2. 　Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia[J]. Blood, 2010, 115(2): 168-186.
3. 　Van Leeuwen EF, van der Ven JT, Engelfriet CP, et al. Specificity of autoantibodies in autoimmune thrombocytopenia[J]. Blood, 1982, 59(1): 23-26.
4. 　Vaughan J, Valbracht J, Nguyen M, et al. Epstein-Bar virus-induced autoimmune responses. I. Immunoglobulin M autoantibodies to proteins mimicking Epstein-Bar virus nuclear antigen-1[J]. J Clin Invest, 1995, 95(3): 1306-1315.
5. 　Schneider P, Mackay F, Steiner V, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth[J]. J Exp Med, 1999, 189(11): 1747-1756.
6. 　Mackay IR, Groom J, Mackay CR. Levels of BAFF in serum in primary biliary cirrhosis and autoimmune diabetes[J]. Autoimmunity, 2002, 35(8): 551-553.
7. 　Schneider P, Tschopp J. BAFF and the regulation of B cell survival[J]. Immunol Lett, 2003, 88(1): 57-62.
8. 　Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease[J]. Nature, 2000, 404(6781): 995-999.
9. 　Reyes S LI, León B F, Rozas V MF, et al. BAFF: a regulatory cytokine of B lymphocytes involved in autoimmunity and lymphoid cancer[J]. Rev Med Chil, 2006, 134(9): 1175-1184.
10. 　Mackay F, Browning JB. A fundamental survival factor for B cells[J]. Nat Rev Immunol, 2002, 2(7): 465-475.
11. 　Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations[J]. J Exp Med, 1999, 190(11): 1697-1710.
12. 　Emmerich F, Bal G, Barakat A, et al. High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura[J]. Br J Haematol, 2007, 136(2): 309-314.
13. 　Mcmillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura[J]. Semin Hematol, 2000, 37(3): 239-248.
14. 　Cines DB, Mckenzie SE, Siegel DL. Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura[J]. J Pediatr Hematol Oncol, 2003, 25(Suppl 1): S52-S56.
15. 　Zhou B, Zhao H, Yang RC, et al. Multi-dysfunctional pathophysiology in ITP[J]. Crit Rev Oncol Hematol, 2005, 54(2): 107-116.
16. 　Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance[J]. Cell, 2000, 101(5): 455-458.
17. 　Sakaguchi S, Toda M, Asano M, et al. T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases[J]. J Autoimmun, 1996, 9(2): 211-220.
18. 　Sakakura M, Wada H, Tawara I, et al. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura[J]. Thromb Res, 2007, 120(2): 187-193.
19. 　Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion Lead to different functional properties[J]. Annu Rev Immunol, 1989, 7: 145-173.
20. 　Panitsas FP, Theodoropoulou M, Kouraklis A, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response[J]. Blood, 2004, 103(7): 2645-2647.
21. 　Wang T, Zhao H, Ren H, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura[J]. Haematologica, 2005, 90(7): 914-923.
22. 　Webber NP, Mascarenhas JO, Crow MK, et al. Functional properties of lymphocytes in idiopathic thrombocytopenic purpura[J]. Hum Immunol, 2001, 62(12): 1346-1355.
23. 　Guo C, Chu X, Shi Y, et al. Correction of Th1-dominant cytokine profiles by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura[J]. J Clin Immunol, 2007, 27(6): 557-562.
24. 　Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nat Immunol, 2005, 6(11): 1123-1132.
25. 　Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 cells[J]. Annu Rev Immunol, 2009, 27: 485-517.
26. 　Zhang J, Ma D, Zhu X, et al. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura[J]. Haematologica, 2009, 94(9): 1326-1329.
27. 　Fridman WH, Bonnerot C, Daeron M, et al. Structural bases of Fc gamma receptor functions[J]. Immunol Rev, 1992, 125: 49-76.
28. 　Maenaka K, van der Merwe PA, Stuart DI, et al. The human low affinity Fcgamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties[J]. J Biol Chem, 2001, 276(48): 44898-44904.
29. 　Takai T. Roles of Fc receptors in autoimmunity[J]. Nat Rev Immunol, 2002, 2(8): 580-592.
30. 　Clarkson SB, Bussel JB, Kimberly RP, et al. Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody[J]. N Engl J Med, 1986, 314(19): 1236-1239.
31. 　Asahi A, Nishimoto T, Okazaki Y, et al. Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcgammaRⅡB in immune thrombocytopenic purpura patients[J]. J Clin Invest, 2008, 118(8): 2939-2949.
32. 　Vainchenker W, Deschamps JF, Bastin JM, et al. Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: immunofluorescent staining and platelet peroxidase detection in megakaryocyte colonies and in in vivo cells from normal and leukemic patients[J]. Blood, 1982, 59(3): 514-521.
33. 　Diggs LW, Hewlett JS. A study of the bone marrow from 36 patients with idiopathic hemorrhagic, thrombopenic purpura[J]. Blood, 1948, 3(10): 1090-1104.
34. 　Kaluzhny Y, Yu G, Sun S, et al. BclxL overexpression in megakaryocytes leads to impaired platelet fragmentation[J]. Blood, 2002, 100(5): 1670-1678.
35. 　Ogilvy S, Metcalf D, Print CG, et al. Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival[J]. Proc Natl Acad Sci USA, 1999, 96(26): 14943-14948.
36. 　Suerbaum S, Michetti P. Helicobacter pylori infection[J]. N Engl J Med, 2002, 347(5): 1175-1186.
37. 　Gasbarrini A, Franceschi F, Tartaglione R, et al. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori[J]. Lancet, 1998, 352(9131): 878.
38. 　Takahashi T, Yujiri T, Shinohara K, et al. Molecular mimicry by Helicobacter pylori CagA protein May be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura[J]. Br J Haematol, 2004, 124(1): 91-96.
39. 　Yamanishi S, Iizumi T, Watanabe E, et al. Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease[J]. Infect Immun, 2006, 74(1): 248-256.
40. 　Yoshimura C, Nomura S, Plasma-soluble fas NM. (APO-1,CD95) and soluble Fas ligand in immune thrombocytopenic purpura[J]. Eur J Haematol, 2000, 64(4): 219-224.
41. 　Du WT, Zhao HF, Xu JH, et al. The role of T-cell immunoglobulin- and mucin-domain-containing molecule-3 polymorphisms in idiopathic thrombocytopenic purpura[J]. Hum Immunol, 2009, 70(6): 398-402.
42. 　Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group[J]. Blood, 2009, 113(11): 2386-2393.
43. 　Stasi R, Amadori S, Osborn J, et al. Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia[J]. PLoS Med, 2006, 3(3): e24.
44. 　侯明. 成人特發(fā)性血小板減少性紫癜診斷和治療專家共識(shí)[J]. 中華血液學(xué)雜志, 2009, 30(9): 647-648.
45. 　中華醫(yī)學(xué)會(huì)血液學(xué)分會(huì)血栓與止血學(xué)組. 成人原發(fā)免疫性血小板減少癥診治的中國專家共識(shí)(修訂版)[J]. 中華血液學(xué)雜志, 2011, 32(3): 214-216.
46. 　Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data[J]. J Thromb Haemost, 2006, 4(11): 2377-2383.
47. 　Arnold DM, Kelton JG. Current options for the treatment of idiopathic thrombocytopenic purpura[J]. Semin Hematol, 2007, 44(4 Suppl 5): S12-S23.
48. 　Neunert C, Lim W, Crowther M, et al. The American society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia[J]. Blood, 2011, 117(16): 4190-4207.
49. 　Kojouri K, Vesely SK, Terrell DR, et al. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications[J]. Blood, 2004, 104(9): 2623-2634.
50. 　Wang T, Xu M, Ji L, et al. Splenectomy for adult chronic idiopathic thrombocytopenic purpura: experience from a single center in China[J]. Eur J Haematol, 2005, 75(5): 424-429.
51. 　Maloisel F, Andrès E, Zimmer J, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results[J]. Am J Med, 2004, 116(9): 590-594.
52. 　Ferrara M, Capozzi L, Russo R. Effect of Helicobacter pylori eradication on platelet count in children with chronic idiopathic thrombocytopenic purpura[J]. Hematology, 2009, 14(5): 282-285.
53. 　Michel M, Cooper N, Jean C, et al. Does helicobater pylori initiate or perpetuate immune thrombocytopenic purpura?[J]. Blood, 2004, 103(3): 890-896.
54. 　Zaja F, Baccarani M, Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia[J]. Blood, 2010, 115(14): 2755-2762.
55. 　Li Z, Mou W, Lu G, et al. Low-dose rituximab combined with short-term glucocorticoids up-regulates Treg cell levels in patients with immune thrombocytopenia[J]. Int J Hematol, 2011, 93(1): 91-98.
56. 　Kuter DJ. New thrombopoietic growth factors[J]. Blood, 2009, 9 Suppl 3(11): S347-S356.
57. 　Cremer M, Schulze H, Linthorst G, et al. Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias[J]. Ann Hematol, 1999, 78(9): 401-407.
58. 　王書杰, 楊仁池, 鄒萍, 等. 重組人血小板生成素治療特發(fā)性血小板減少性紫癜的多中心隨機(jī)對照臨床試驗(yàn)[J]. 血栓與止血學(xué), 2010, 16(4): 149-153, 157.
59. 　Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl[J]. Cytokine, 2004, 25(2): 52-60.
60. 　Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP[J]. Blood, 2009, 113(10): 2161-2171.
  1. 1. 　Watson-Williams EJ, Macpherson AI, Davidson S. The treatment of idiopathic thrombocytopenic purpura: a review of ninety-three cases[J]. Lancet, 1958, 2(7040): 221-226.
  2. 2. 　Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia[J]. Blood, 2010, 115(2): 168-186.
  3. 3. 　Van Leeuwen EF, van der Ven JT, Engelfriet CP, et al. Specificity of autoantibodies in autoimmune thrombocytopenia[J]. Blood, 1982, 59(1): 23-26.
  4. 4. 　Vaughan J, Valbracht J, Nguyen M, et al. Epstein-Bar virus-induced autoimmune responses. I. Immunoglobulin M autoantibodies to proteins mimicking Epstein-Bar virus nuclear antigen-1[J]. J Clin Invest, 1995, 95(3): 1306-1315.
  5. 5. 　Schneider P, Mackay F, Steiner V, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth[J]. J Exp Med, 1999, 189(11): 1747-1756.
  6. 6. 　Mackay IR, Groom J, Mackay CR. Levels of BAFF in serum in primary biliary cirrhosis and autoimmune diabetes[J]. Autoimmunity, 2002, 35(8): 551-553.
  7. 7. 　Schneider P, Tschopp J. BAFF and the regulation of B cell survival[J]. Immunol Lett, 2003, 88(1): 57-62.
  8. 8. 　Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease[J]. Nature, 2000, 404(6781): 995-999.
  9. 9. 　Reyes S LI, León B F, Rozas V MF, et al. BAFF: a regulatory cytokine of B lymphocytes involved in autoimmunity and lymphoid cancer[J]. Rev Med Chil, 2006, 134(9): 1175-1184.
  10. 10. 　Mackay F, Browning JB. A fundamental survival factor for B cells[J]. Nat Rev Immunol, 2002, 2(7): 465-475.
  11. 11. 　Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations[J]. J Exp Med, 1999, 190(11): 1697-1710.
  12. 12. 　Emmerich F, Bal G, Barakat A, et al. High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura[J]. Br J Haematol, 2007, 136(2): 309-314.
  13. 13. 　Mcmillan R. Autoantibodies and autoantigens in chronic immune thrombocytopenic purpura[J]. Semin Hematol, 2000, 37(3): 239-248.
  14. 14. 　Cines DB, Mckenzie SE, Siegel DL. Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura[J]. J Pediatr Hematol Oncol, 2003, 25(Suppl 1): S52-S56.
  15. 15. 　Zhou B, Zhao H, Yang RC, et al. Multi-dysfunctional pathophysiology in ITP[J]. Crit Rev Oncol Hematol, 2005, 54(2): 107-116.
  16. 16. 　Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance[J]. Cell, 2000, 101(5): 455-458.
  17. 17. 　Sakaguchi S, Toda M, Asano M, et al. T cell-mediated maintenance of natural self-tolerance: its breakdown as a possible cause of various autoimmune diseases[J]. J Autoimmun, 1996, 9(2): 211-220.
  18. 18. 　Sakakura M, Wada H, Tawara I, et al. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura[J]. Thromb Res, 2007, 120(2): 187-193.
  19. 19. 　Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion Lead to different functional properties[J]. Annu Rev Immunol, 1989, 7: 145-173.
  20. 20. 　Panitsas FP, Theodoropoulou M, Kouraklis A, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response[J]. Blood, 2004, 103(7): 2645-2647.
  21. 21. 　Wang T, Zhao H, Ren H, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura[J]. Haematologica, 2005, 90(7): 914-923.
  22. 22. 　Webber NP, Mascarenhas JO, Crow MK, et al. Functional properties of lymphocytes in idiopathic thrombocytopenic purpura[J]. Hum Immunol, 2001, 62(12): 1346-1355.
  23. 23. 　Guo C, Chu X, Shi Y, et al. Correction of Th1-dominant cytokine profiles by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura[J]. J Clin Immunol, 2007, 27(6): 557-562.
  24. 24. 　Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nat Immunol, 2005, 6(11): 1123-1132.
  25. 25. 　Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 cells[J]. Annu Rev Immunol, 2009, 27: 485-517.
  26. 26. 　Zhang J, Ma D, Zhu X, et al. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura[J]. Haematologica, 2009, 94(9): 1326-1329.
  27. 27. 　Fridman WH, Bonnerot C, Daeron M, et al. Structural bases of Fc gamma receptor functions[J]. Immunol Rev, 1992, 125: 49-76.
  28. 28. 　Maenaka K, van der Merwe PA, Stuart DI, et al. The human low affinity Fcgamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties[J]. J Biol Chem, 2001, 276(48): 44898-44904.
  29. 29. 　Takai T. Roles of Fc receptors in autoimmunity[J]. Nat Rev Immunol, 2002, 2(8): 580-592.
  30. 30. 　Clarkson SB, Bussel JB, Kimberly RP, et al. Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody[J]. N Engl J Med, 1986, 314(19): 1236-1239.
  31. 31. 　Asahi A, Nishimoto T, Okazaki Y, et al. Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcgammaRⅡB in immune thrombocytopenic purpura patients[J]. J Clin Invest, 2008, 118(8): 2939-2949.
  32. 32. 　Vainchenker W, Deschamps JF, Bastin JM, et al. Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: immunofluorescent staining and platelet peroxidase detection in megakaryocyte colonies and in in vivo cells from normal and leukemic patients[J]. Blood, 1982, 59(3): 514-521.
  33. 33. 　Diggs LW, Hewlett JS. A study of the bone marrow from 36 patients with idiopathic hemorrhagic, thrombopenic purpura[J]. Blood, 1948, 3(10): 1090-1104.
  34. 34. 　Kaluzhny Y, Yu G, Sun S, et al. BclxL overexpression in megakaryocytes leads to impaired platelet fragmentation[J]. Blood, 2002, 100(5): 1670-1678.
  35. 35. 　Ogilvy S, Metcalf D, Print CG, et al. Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival[J]. Proc Natl Acad Sci USA, 1999, 96(26): 14943-14948.
  36. 36. 　Suerbaum S, Michetti P. Helicobacter pylori infection[J]. N Engl J Med, 2002, 347(5): 1175-1186.
  37. 37. 　Gasbarrini A, Franceschi F, Tartaglione R, et al. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori[J]. Lancet, 1998, 352(9131): 878.
  38. 38. 　Takahashi T, Yujiri T, Shinohara K, et al. Molecular mimicry by Helicobacter pylori CagA protein May be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura[J]. Br J Haematol, 2004, 124(1): 91-96.
  39. 39. 　Yamanishi S, Iizumi T, Watanabe E, et al. Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease[J]. Infect Immun, 2006, 74(1): 248-256.
  40. 40. 　Yoshimura C, Nomura S, Plasma-soluble fas NM. (APO-1,CD95) and soluble Fas ligand in immune thrombocytopenic purpura[J]. Eur J Haematol, 2000, 64(4): 219-224.
  41. 41. 　Du WT, Zhao HF, Xu JH, et al. The role of T-cell immunoglobulin- and mucin-domain-containing molecule-3 polymorphisms in idiopathic thrombocytopenic purpura[J]. Hum Immunol, 2009, 70(6): 398-402.
  42. 42. 　Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group[J]. Blood, 2009, 113(11): 2386-2393.
  43. 43. 　Stasi R, Amadori S, Osborn J, et al. Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia[J]. PLoS Med, 2006, 3(3): e24.
  44. 44. 　侯明. 成人特發(fā)性血小板減少性紫癜診斷和治療專家共識(shí)[J]. 中華血液學(xué)雜志, 2009, 30(9): 647-648.
  45. 45. 　中華醫(yī)學(xué)會(huì)血液學(xué)分會(huì)血栓與止血學(xué)組. 成人原發(fā)免疫性血小板減少癥診治的中國專家共識(shí)(修訂版)[J]. 中華血液學(xué)雜志, 2011, 32(3): 214-216.
  46. 46. 　Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data[J]. J Thromb Haemost, 2006, 4(11): 2377-2383.
  47. 47. 　Arnold DM, Kelton JG. Current options for the treatment of idiopathic thrombocytopenic purpura[J]. Semin Hematol, 2007, 44(4 Suppl 5): S12-S23.
  48. 48. 　Neunert C, Lim W, Crowther M, et al. The American society of hematology 2011 evidence-based practice guideline for immune thrombocytopenia[J]. Blood, 2011, 117(16): 4190-4207.
  49. 49. 　Kojouri K, Vesely SK, Terrell DR, et al. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications[J]. Blood, 2004, 104(9): 2623-2634.
  50. 50. 　Wang T, Xu M, Ji L, et al. Splenectomy for adult chronic idiopathic thrombocytopenic purpura: experience from a single center in China[J]. Eur J Haematol, 2005, 75(5): 424-429.
  51. 51. 　Maloisel F, Andrès E, Zimmer J, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results[J]. Am J Med, 2004, 116(9): 590-594.
  52. 52. 　Ferrara M, Capozzi L, Russo R. Effect of Helicobacter pylori eradication on platelet count in children with chronic idiopathic thrombocytopenic purpura[J]. Hematology, 2009, 14(5): 282-285.
  53. 53. 　Michel M, Cooper N, Jean C, et al. Does helicobater pylori initiate or perpetuate immune thrombocytopenic purpura?[J]. Blood, 2004, 103(3): 890-896.
  54. 54. 　Zaja F, Baccarani M, Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia[J]. Blood, 2010, 115(14): 2755-2762.
  55. 55. 　Li Z, Mou W, Lu G, et al. Low-dose rituximab combined with short-term glucocorticoids up-regulates Treg cell levels in patients with immune thrombocytopenia[J]. Int J Hematol, 2011, 93(1): 91-98.
  56. 56. 　Kuter DJ. New thrombopoietic growth factors[J]. Blood, 2009, 9 Suppl 3(11): S347-S356.
  57. 57. 　Cremer M, Schulze H, Linthorst G, et al. Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias[J]. Ann Hematol, 1999, 78(9): 401-407.
  58. 58. 　王書杰, 楊仁池, 鄒萍, 等. 重組人血小板生成素治療特發(fā)性血小板減少性紫癜的多中心隨機(jī)對照臨床試驗(yàn)[J]. 血栓與止血學(xué), 2010, 16(4): 149-153, 157.
  59. 59. 　Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl[J]. Cytokine, 2004, 25(2): 52-60.
  60. 60. 　Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP[J]. Blood, 2009, 113(10): 2161-2171.