原發免疫性血小板減少癥研究進展_《華西醫學》

作者：

李艷秋 ,  牛挺

四川大學華西醫院血液科血液學研究室（成都，610041）;

關鍵詞：

原發免疫性血小板減少癥發病機制診斷治療

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原發免疫性血小板減少癥（ITP）是一種常見的出血性疾病，其發病機制仍不十分清楚。現有治療方案在ITP的治療中取得一定的療效，如糖皮質激素、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發難治的問題。現將近年ITP發病機制、診斷和治療等方面的研究進展作一綜述。

引用本文： 李艷秋,牛挺. 原發免疫性血小板減少癥研究進展. 華西醫學, 2012, 27(10): 1570-1574. doi: 復制

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. 成人特發性血小板減少性紫癜診斷和治療專家共識[J]. 中華血液學雜志, 2009, 30(9): 647-648.
45.	中華醫學會血液學分會血栓與止血學組. 成人原發免疫性血小板減少癥診治的中國專家共識(修訂版)[J]. 中華血液學雜志, 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性血小板減少性紫癜的多中心隨機對照臨床試驗[J]. 血栓與止血學, 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. 　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. 成人特發性血小板減少性紫癜診斷和治療專家共識[J]. 中華血液學雜志, 2009, 30(9): 647-648.
45. 　中華醫學會血液學分會血栓與止血學組. 成人原發免疫性血小板減少癥診治的中國專家共識(修訂版)[J]. 中華血液學雜志, 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性血小板減少性紫癜的多中心隨機對照臨床試驗[J]. 血栓與止血學, 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.

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原發免疫性血小板減少癥研究進展

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《華西醫學》

原發免疫性血小板減少癥研究進展

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