芪龙颗粒治疗难治性特发性血小板减少性紫癜临床设计和实施
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
常规应用糖皮质激素和脾脏切除术可使70%以上的特发性血小板减少性紫癜(ITP)患者血小板数量稳定在安全水平,约30%患者使用这些措施无效,这部分患者即属于难治性特发性血小板减少性紫癜(RITP)范围。RITP具有效果差、易反复等特征,故治疗非常棘手。药物联合是RITP治疗的一大特点,但文献报道疗效差异很大,且治疗周期较长,停药后复发率高,不良反应明显,药物毒副作用导致的危害可能高于疾病本身,同时,部分药物价格昂贵,使相关的治疗费用上扬,也限制了临床应用。中西医结合治疗RITP前景可观。
     联合中医药治疗,可使RITP患者外周血小板计数维持在安全水平,并且改善临床症状,提高患者生活质量。但是,就中医药临床研究而言,存在①辨证论治无明显规律可寻;②临床研究客观性、真实性和可重复性有待提高;③安全性研究有待深入等不足,难以真正体现中医药的内在价值。
     通过长期的临床观察,我们提出“气虚血瘀”是RITP的主要病机,并拟定了“益气活血”的治则,为了客观地证实芪龙颗粒治疗“气虚血瘀”型RITP的临床疗效,我们在国内首次采用了目前公认最先进的随机对照试验(RCT)设计思路,严格临床病例纳入、排除标准及疗效评估标准,并制定临床病例报告表,进行多中心临床观察。本课题因此被首都医学发展基金批准为2005年度中医临床研究自主创新课题(课题编号:SF-2005-031)。
     课题目前尚未完成,在具体的临床试验工作中,我们遇到了一些问题和不足,同时也在解决问题中逐渐完善自我,芪龙颗粒治疗RITP的客观临床疗效有待在课题完成后进一步揭示。
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelets and bleeding,about one thrid of adults with ITP do not respond to standard doses of corticosteroids and aplenectomy and require anther therapy to raise their platelet count, those patients belong to Refractory Idiopathic thrombocytopenia purpura(RITP). The treatment of RITP is barely effective and some patients will relapse within given period.
     At present, multiple treatments play a more important method in RITP of adult, but response rates are low, or long treatment periods, or high relapse rate,or serious side effects against their use. However, the goal of treatment for patients with ITP is not to cure the RITP, but raise the platelet count high enough levels to prevent bleeding using the least toxic therapy. So the integration of traditional and western medicine is one of promising treatments for RITP.
     Through the integration of traditional and western medicine, paitents of RITP can maintain a high level of platelet count and improve clinic symptom ,but there are some lacks in traditional Chinese medicine clinic test, such as absencing rules of the treatment based on syndrome differentiation, less objectivity, authernicity and long term security.
     In the theory of traditional Chinese medicine, blood stasis due to qi deficiency is the essential mechanism of RITP. According to the pathogens, the treatment is supplementing qi, promoting blood circulation for removing blood stasis. we use Qi Long granule as therapy medicine, set a randomized controlled trials (RCTs) to evaluate clinic curative effect of RITP,which is the first time we do this job in traditional Chinese medicine of RITP. So this study is authorized self-determination innovated study in traditional Chinese medicine in 2005 by the fund of medicine development in Beijing (number: SF-2005-031) .
     At present, the study is not accomplished, wo met a lot of problems in the clinic test and at the same time we improve ourslves, which make our study more scientific and external, In 2009 we can finish the study and report the clinic curative effect of Qi Long granule for RITP.
引文
1.张之南,主编.血液病诊断及疗效标准.第二版.北京:科技出版社,1998,279-285
    2.陈灏珠,主编.实用内科学.第11版.北京:人民卫生出版社,2002,2223-2224)
    3.江尚飞.黄芪现代应用综述.中国药业.2007,16(18):62-63
    4.张小梅.黄芪多糖的免疫调节作用及抗肿瘤作用研究进展.大连大学学报.2003,24(6):101-104
    5.李曰庆.黄芪的药理药效研究进展.医药产业资讯.2006,3(11):128-129
    6.汪德清,田亚平,宋淑珍,等.黄芪总黄酮抗突变作用实验研究.中国中药杂志.2003,28(12):1164-1167
    7.高巍,赵铁华.穿山龙总皂苷对小鼠免疫功能的影响.承德中医学院学报.2001,18(1):9-10
    8.南景一,王忠,杨正娟等.穿山龙对小鼠免疫功能的影响.中草药.1998,19(13):22-22
    9.George JN,Woolf SH,Raskob GE,et al.Idiopathic thrombocytopenic purpura a practice guideline developed by explicitmethods for the american society of hematology.Blood.1996,88:33-40
    10.单渊东.进一步规范药品临床试验.中华医学杂志.2002,82(12):793-795
    11.苏炳华,王纪佐,凌静萍等.双盲临床实验的进一步探讨.中国卫生统计,1999,16(4):253
    1.George JN,Woolf SH,Raskob GE,et al.Idiopathic thrombocytopenic purpura a practice guideline developed by explicitmethods for the american society of hematology.Blood.1996,88:33-40
    2.张敬宇,徐世荣.成人慢性难治性特发性血小板减少性紫癜的治疗进展.临床血液学杂志.2002,15(6):272-276
    3.难治性特发性血小板减少性紫癜的治疗进展.疑难病杂志.2006,5(5):395-397
    4.Robert McMillan.Therapy for Adults with Refractory Chronic Immune Thrombocytopenic Purpura.Annals of Internal Medicine,1997,126:307-314
    5.龚明,应城.大剂量地塞米松联合长春新碱治疗慢性难治性特发性血小板减少性紫癜的临床观察.内科急危重症杂志.2005,11(3):146-146
    6.丁时义.甲基强的松龙冲击治疗特发性血小板减少性紫癜12例.临床医学.2004,24(12):8-9
    7.曹红,马春蓉,臧泽林.甲基强的松龙冲击治疗重症特发性血小板减少性紫癜.华西医学.2006,21(1):36-37
    8.周建尧,冯幼菊.他莫昔芬辅助治疗9例难治性血特发性小板减少性紫癜患者临床观察.浙江医学.2002,24(12):755-755
    9.Kappers-Klunne MC,van't Veer MB.Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy.Br J Haematol,2001,114(1):121-125
    10.Giovanni Emilia,Monica Morselli,Mario Luppi,et al.Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.Blood,2002,99:1482-1485
    11.张丽丽,乔振华.环孢素A治疗难治性特发性血小板减少性紫癜15例疗效观察.中国药物与临床.2005,5(9):704-705
    12.万幼峰,陈协群,白庆成,等.环孢素A治疗难治性特发性血小板减少性紫癜的临床疗效观察.临床军医杂志.2005,33(6):687-688
    13.赵亮,徐春雨,赵健康.赛斯平治疗难治性特发性血小板减少性紫癜27例临床观察.临沂医专学报.2001,23(2):144-145
    14.Shirota T,Yamamoto H,Fujimoto H,et al.Cyclic thrombocytopenia in a patient treated with cyclosporine for refractory idiopathic thrombocytopenic purpura.Am J Hematol,1997,56(4):272-276
    15.张之南主编.血液病诊断及疗效标准.第2版.北京:科学出版社,1998.279-285
    16.洪少杰 唐小玲.霉酚酸酯治疗难治性特发性血小板减少性紫癜16例疗效观察.中国实用内科杂志.2005,25(6):531-532
    17.侯明,冀学斌,彭军,等.霉酚酸酯治疗激素耐药特发性血小板减少性紫癜的疗效和机制研究.中华血液学杂志.2003,24(9):498-499
    18.季林祥,杨德光,王玫,等.西艾克治疗特发性血小板减少性紫癜疗效观察.中华血液学杂志,1995,16(3):142-142
    19.彭澎,罗晓明,周馥英,等.长春新碱治疗14例难治性特发性血小板减少性紫癜患儿疗效分析.浙江医学.2003,25(9):567-568
    20.陈宇辉,周大成,胡学婷.长春新碱与长春地辛治疗难治性血特发性小板减少性紫癜的临床观察.吉林医学.2004,25(2):74-74
    21.邓承琪,牛挺,向晓娟,等.干扰素治疗慢性特发性血小板减少性紫癜的临床探讨.华西医科大学学报,2000,31(3):392-395
    22.Dikici B,Bosnak M,Kara IH,et al.Interferon-alpha therapy in idiopathic thrombocytopenic purpura.Pediatr Int,2001,43(6):577-80
    23.Donato H,Kohan R,Picon A,et al.Alpha-interferon therapy induss improvement of platelet counts in children with chronic idiopathic thrombocypenic purpura.J Pediatr Hematol Oncol.2001,23(9):598-603
    24.梁欣荃,王志华,祝平安.干扰素治疗难治性特发性血小板减少性紫癜疗效观察.中国医师杂志.2005,7(5):307-308
    25.Saitoh M,Taguchi K,Momose K,et al.Recombinant human interleukin-11 improved carboplatin-induced thrombocytopenia without affecting antitumor activities in mice beating lewis lung carcinoma cells.Cancer Chenother Phamacol.2002,49(2):161-166
    26.唐雪梅,廖小梅,牛挺,等.白细胞介素-11对CITP患者骨髓巨核细胞的影响.临床血液学杂志,2001,14(5):205-207
    27.张秋荣,吴德沛,陈令松,等.rhIL-11治疗慢性特发性血小板减少性紫癜的疗效观察.中国实验血液学杂志.2006,14(1):176-178
    28.赵毅,张学进,杨玮,等.重组人白细胞介素-11治疗难治性血特发性小板减少性紫癜7例临床分析.浙江医学.2005,27(12):903-904
    29.陈曙平,何群,吴登蜀,等.重组人白细胞介素-11治疗慢性难治性特发性血小板减少性紫癜的临床观察.中国医学工程.2006,14(4):417-419
    30.肖红,彭秀兰,刘华东.重组人白细胞介素-11治疗成人慢性难治性特发性血小板减少性紫癜临床观察.中国现代医学杂志.2007,17(8):993-995
    31.任立红,任志民,薛凤兰,等.丙种球蛋白与甲基强的松龙联合治疗儿童难治性血小板减少性紫癜.哈尔滨医科大学学报.1996,30(6):576-577
    32.Samuelsson A,Towers TL,Ravetch JV.Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor.Science.2001 Jan 19;291(5503):484-648.
    33.杨小英.丙种球蛋白治疗成人难治性特发性血小板减少性紫癜32例.广东医学院学报.2002,20(4):304-304
    34.粟世勇.小剂量静注丙球治疗难治性免疫性血小板减少性紫癜疗效观察.广西医科大学学报.2003,20(3):437-437
    35.蒋维国.小剂量丙种球蛋白治疗难治性ITPl6例疗效观察.中国小儿血液,1997,2(5):230-230
    36.Stefan Christiansen,Christof Schmid,Klaus Redmann,et al.Preoperative immunoglobulin treatment in patients with Werlhof's disease undergoing cardiac operation.Ann.Thorac.Surg.2000,69:61-64
    37.TM Cosgriff,ML Black,W Stein 3rd.Successful treatment of severe refractory idiopathic thrombocytopenic purpura with liposomal doxorubicin.Am J Hematol,1998,57(1):8-9
    38.Salama A,Kiefel V,Amberg R,et al.Treatment of autoimmune thrombocytopenic purpura with Rhesusantibodies[anti Rh(D)].Blut,1984,49(1):29-35
    39.Salama A,Kiefel V,Mueller Eckhardt C.Effect of IgG anti-Rho(D)in adult patients with chronic autoimmune thrombocytopenic purpura.Am J Hematol,1986,22(3):241-250
    40.Bussel JB,Graziano JN,Kimberly RP,et al.Intravenous anti-D treatment of immune thrombocytopenic purpura:analysis of efficacy,toxicity,and mechanism of effect.Blood,1991,77(9):1884-1893
    41.Scaradavou A,Woo B,Woloski BM,et al.Intravenous anti-D treatment of immune thrombocytopenic purpura:Experience in 272 patients.Blood,1997,89(8):2689-2700
    42.Gaines AR.Acute on sethemoglobinuria and sequelae follow in gRh(D)immune globulin intravenous administration in immune thrombocytopenic purpura patients.Blood,2000,95(8):2523-2529
    43.Bussel JB.Recent advances in the treatment of idiopathic thrombocytopenic purpura:the anti-D clinical experiences.Semin Hematol,1998,35(1):1-4
    44.Waintraub SE,Brody JI.Use of anti D immune thrombocytopenicpur pura as a means to prevent splenctomy.Sem in Hematol.2000,37(suppl):45-49
    45.Newmain GC,Novoa MV,fodero EM,et al.A dose of 75microg/kg/d of i.v.anti Dincreases the platelet count more rapidly and for alonger period of more than 50microg/kg/d in adults with immune thrombocytopenic purpura.Br J Hematol.2001,112:1076-1078
    46.Sajid R,Adil SN,Fadoo Z,et al.Use of in travenous anti D in patients with refractory and relapsed immune thrombocytopenic purpu ra.J Pak Med Assoc.2003,53(11):537-539
    47.Cooper N,Woloski BM,Fodero EM,et al.Does treatment infusions of intravenous anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura to avoid sp;emectomy.Blood.2002,99(6):922-1927
    48.Song S,Crow AR,Siragam V,et al.Monoclonal antibodies that mimic the action of anti-D in the amelioration of murine ITP act by a mechanism distinct from that of IVIg.Blood.2005,105(5):1546-1548
    49.Hoshi S,Yoshitomi H.Megakaryocytopoietic activity of atruncated variant of mouse thrombopietin.J Biophys Commun 1997,231:823-823
    50.杨玲,尚学琴,佟力.血小板减少症患者促血小板生成素和血清白细胞介素-11水平的检测.白血病.淋巴瘤.2006,15(2):115-117
    51.肖燕,林雯,刘勤.血小板生成素和巨核细胞对特发性血小板减少性紫癜患儿预后的影响.实用儿科临床杂志.2006,21(15):987-988
    52.赵永强,王庆余,瞿明,等.重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床研究.中华内科杂志.2004,43(8):608-610
    53.吴秋玲、何静、陈燕,等.重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的临床研究.华中科技大学学报(医学版).2004,33(3):297-299
    54.何晖.抗CD20单克隆抗体美罗华的临床研究进展.中国医师杂志.2006,8(3):431-432
    55.Stasi R,Stipa E,Forte V,etal.Variablepatems of responset orituximab in adults witchronicidiopathic thrombocy to penicpurpura.Blood.2002,99:3872-3873
    56.Perotta A,Sunneberg TA,Scott J,et al.Rituxin in zhe treatment of chronic idiopathic thrombocytopenic purpura.Blood.1999,94:49a
    57.Stasi R,Pagano A,Stipa E,et al.Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura.Blood.2001,98(4):952-957
    58.Stasi R,Stipa E,Forte V,et al.Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura.Blood.2002,99:3872-3873
    59.Giagounidis AA,Anhuf J,Schneider P,et al.Treatment of relapsed idiopathic throm bocytopenic purpura with the anti-CD20 monoclonal antibody rituximab:apilotstudy.EurJHeamatol.2002,69(2):95-100
    60.Cooper N,Stasi R,CunningghamRundles S,etal.Theefficacy and safety of Bcelldepletion with antiCD20 monoclonal antibody in adults with chronicimmunethrombocy to penicpurpura.BrJHaematol,2004,125:232-239
    61.邹农,华宝来,王书杰,等.利妥昔单抗治疗难治性特发性血小板减少性紫癜一例.中华医学杂志.2005,85(6):432-432
    62.许改香,钱文斌.美罗华和脾切除术治疗难治性特发性血小板减少性紫癜1例.浙江医学.2005,27(8):618-618
    63.卢文静,译.用美罗华治疗难治性血栓性血小板减少性紫癜发生心源性休克的成功救治.国外医学输血及血液学分册.2006,29(3):245-245
    64.Willis F,Marsh JC,Bevan DH,et al.The effect of treatment with CaMPath-1H in patients with autoimmune cytopenias.Br J Haematol,2001,114(4):891-892
    65.徐欣欣.难治性特发性血小板减少性紫癜的靶向治疗.国外医学内科学分册2004,31(7):308-311
    66.Nagahama M,Nascarenhas S,Kanazawa S,et al.Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura.Eur J Hae mate.2002,69(5-6):303-308
    67.Bussel JB.Overview of idiopathic thrombocytopenic purpura:new approach to refractory patients.Semin Oncol.2000,27(12):91-98
    68.Kuwana M,Nomura S,Fujimura K,teal.Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura.Blood.2004,103(4):1229-1236
    69.宝国秀,杨玲.干扰素联合长春新碱、泼尼松治疗慢性难治性特发性血小板减少性紫癜.中国煤炭工业医学杂志.2004,7(6):508-508
    70.张敬宇,杨琳,罗建民,等.环孢菌素A联合小剂量泼尼松治疗难治性特发性血小板减少性紫癜.医师进修杂志.2004,27(9):32-33
    71.郭熙哲,潘敬新,唐文清.大剂量甲基强的松龙联合较小剂量丙种球蛋白治疗重症ITP疗效观察.中国误诊学杂志.2005,5(2):303-304
    72.金洁萍,李红艳,张欣.丙种球蛋白联合长春新碱治疗难治性ITP.中国医师杂志.2005,7(5):711-712
    73.徐静,仇惠英.利妥昔单抗联合环孢素治疗难治性特发性血小板减少性紫癜1例.临床荟萃.2007,22(15):1122-1123
    74.陶洁,黄颖,李洪强,等.联合化疗治疗成人慢性难治性特发性血小板减少性紫癜.中国综合临床.2007,23(6):489-491
    75.吴稚冰.细胞保护剂amifostifostine的临床研究.实用肿瘤杂志.2003,18(4):339-341
    76.果丽实,刘艳春,徐琪,等.氨磷汀联合中剂量丙种球蛋白治疗12例难治性特发性血小板减少性紫癜患者近期疗效观察.临床荟萃.2007,22(20):1459-1460
    77.Lagarez FM,Fuertes FF,Cabrezo TH,et al.CoMPlete splenic embolization in the treatment of immune thrombocytopenic purpura.Br J Haematol,1998,103(3):894-895
    78.宋节,王军业,李晓明.部分脾栓塞治疗难治性血小板减少性紫癜.山东医药,1999,39(10):37-37
    79.李雁恩,陈丽蓉,王晓宏.脾部分栓塞治疗难治性血小板减少性紫癜.实用儿科临床杂志,1999,15(5):260-260
    80.杨光,夏国强,梁红,等.脾栓塞治疗难治性、免疫性血小板减少性紫癜.哈尔滨医科大学学报,1997,2:177-178
    81.张文娟,常靖,郑雪梅.脾动脉栓塞治疗慢性特发性血小板减少性紫癜临床疗效分析.实用医技杂志.2007,14(4):443-444
    82.Kayano M,Takazawa K,Ogura T.Idiopathic thrombocytopenic purpura treated with splenic irradiation.Nippon Naika Gakkai Zasshi.2002,91(2):728-730
    83.Calverley DC,Jones GW,Kelton JG.Splenic radiation for corticosteroid-resistant thrombocypenia.Ann Intern Mde.1992,116(12):977-981
    84.姜玉华,陈学良,程玉峰,等.脾脏放射治疗老年人难治性原发性血小板减少性紫癜17例报告.山东大学学报(医学版).2005,43(4):367-369
    85.N Vianelli,L Gugliotta,L Gianni,et al.Ascorbic acid for the treatment of chronic refractory idiopathic thrombocytopenic purpura(ITP).Haematologica.1992,77(1):92-93
    86.沈建箴,郭瑞官,李健,等.四种方案治疗难治性原发性血小板减少性紫癜的疗效.福建医学院学报,1996,30(1):69-70
    87.孙玲,孙慧,陈绍倩,等.大剂量维生素C治疗难治性特发性血小板减少性紫癜14例.郑州大学学报(医学版).2003,38(6):983-983
    88.滕占庆.注射用维生素C治疗血小板减少性紫癜疗效观察.药物与临床.2006,14(3):222-223
    89.Brox AG,Howson-Jan K,Fauser AA.Treatment of idiopathic thrombocytopenic purpura with ascorbate.Br J Heamatol.1988,70(3):341-341
    90.Goto H,Kikuta T,Ota A,et al.Successful treatment of refractory idiopathic thrombocytopenic purpura by eradication of Helicobacter pylori.Rinsho Ketsueki.2001,42(12):1192-1194
    91.孙达春,李小亮,张爱华,等.根除幽门螺旋杆菌疗法治疗难治性免疫性血小板减少性紫癜.血栓与止血学.2006,12(4):163-165
    92.李红华,达万明.抗幽门螺杆菌治疗对慢性特发性血小板减少性紫癜患者疗效观察.中国实用内科杂志.2005,25(10):909-910
    93.陈登科,李沁.慢性特发性血小板减少性紫癜与抗幽门螺杆菌治疗关系的临床观察.贵州医学杂志.2006,30(11):1024-1025
    94.李慧,刘霆,孟文彤.幽门螺杆菌感染与慢性特发性血小板减少性紫瘫的临床观察.血栓和止血学.2006,12(4):160-162
    95.阮林海,郭艳珍,王瑞丽,等.2:2:1置换液血浆置换治疗难治性特发性血小板减少性紫癜临床研究.中国综合临床.2001,17(6):434-435
    96.张薇,周道斌,赵岩,等.自体外周血干细胞移植治疗难治性免疫性血小板减少性紫癜及随访.基础医学与临床.2007,27(5):573-576
    97.Seach HL,Jonathan K,Ala AS etal.Peripheral bloodstem cell transplantation for refratory auto immune thrombocytopenic pupura.Lancet.1997,349:475-475
    98.Richard D,Patrick F,Nakamura R,et al.High-dose cyclophopamide with autologous lymphocyte depleted peripheral blood support for treatmeat of refactory chronic auto immune thrombocytopenia.Blood.2003,101:71-77
    99.张薇,周道斌,赵岩,等.自体外周血干细胞移植治疗难治性免疫性血小板减少性紫癜及随访.基础医学与临床.2007,27(5):573-576
    1.郝思国.大剂量甲基泼尼松龙冲击治疗重症特发性血小板减少性紫癜.安徽医科大学学报.1999,34(2):123-124
    2.丁时义.甲基强的松龙冲击治疗特发性血小板减少性紫癜12例.临床医学.2004,24(12):8-9
    3.林凤茹,王艳,姚尔固.难治性特发性血小板减少性紫癜的诊断与治疗.临床荟萃.2001,16(24):1135-1137
    4.曹红,马春蓉,臧泽林,等.甲基强的松龙冲击治疗重症特发性血小板减少性紫癜.华西医学.2006,21(1):36-37
    5.秦平,陈峰,张春青,等.大剂量地塞米松治疗慢性特发性血小板减少性紫癜的疗效观察.中华内科杂志.2005,44(6):451-452
    6.杜艳林,王泽民,陈广垠.大剂量甲基强的松龙联合中药治疗重症特发性血小板减少性紫癜疗效观察.医学综述.2007,13(23):1869-1870
    7.章秀珍,许多荣,洪文德,等.环孢素A对难治性免疫性血小板减少性紫癜的治疗.临床血液学杂志.1999,12(6):266-267
    8.朱维强.环孢素A治疗难治性特发性血小板减少性紫癜9例疗效观察.中华内科杂志.1999,38(4):265-266
    9.段婷,常瑛,刘锦丽.环孢素A治疗难治性特发性血小板减少性紫癜的近期疗效观察.中华内科杂志.2000,39(9):630
    10.王明琳,刘传印,吴红光,等.环孢素A治疗难治性特发性血小板减少性紫癜的近期疗效.临床血液学杂志.2001,14(1):34-35
    11.王琳,陈建华,苏春晓.环孢素A治疗难治性血小板减少性紫癜8例分析.山西医药.2001,6:521-522
    12.赵亮,徐春雨,赵健康,等.赛斯平治疗难治性特发性血小板减少性紫癜27例临床观察.临沂医专学报.2001,23(2):144-145
    13.张丽丽,乔振华.环孢素A治疗难治性特发性血小板减少性紫癜15例疗效观察.中国药物与临床.2005,5(9):704-705
    14.万幼峰,陈协群,白庆咸,等.环孢素A治疗难治性特发性血小板减少性紫癜的临床疗效观察.临床军医杂志.2005,33(6):687-688
    15.季林祥,杨德光,王玫.西艾克治疗特发性血小板减少性紫癜疗效观察.中华血液学杂志.1995,16(3):142-142
    16.沈建箴,郭瑞官,李健.四种方案治疗难治性原发性血小板减少性紫癜的疗效.福建医学院学报.1996,30(1):69-70
    17.徐钰荣,郭瑞官.西艾克与达那唑联合治疗难治性小儿血小板减少性紫癜.临床血液 学杂志.2000,13(3):136-136
    18.彭澎,罗晓明,周馥英.长春新碱治疗14例难治性特发性血小板减少性紫癜患儿疗效分析.浙江医学.2003,25(9):567-568
    19.陈宇辉,周大成,胡学婷.长春新碱与长春地辛治疗难治性血小板减少性紫癜的临床观察.吉林医学.2004,25(2):74-74
    20.接贵涛,王彦丽.长春新碱治疗难治性特发性血小板减少性紫癜疗效分析.社区医学杂志.2008,6(4):23-24
    21.任立红,任志民,薛凤兰.丙种球蛋白与甲基强的松龙联合治疗儿童难治性血小板减少性紫癜.哈尔滨医科大学学报.1996,30(6):576-577
    22.刘欣、蔡晓燕、余自强.静注免疫球蛋白治疗难治性特发性血小板减少性紫癜.中国输血杂志.1998,11(1):16-17
    23.殷建秀、付秋德.静脉中剂量丙种球蛋白治疗难治性特发性血小板减少性紫癜12例疗效观察.医学理论与实践1999,12(11):672-673
    24.张君丽、周海岚、钱红兰.静注丙球治疗难治性特发性血小板减少性紫癜疗效观察.温州医学院学报.2000,30(2):139-140
    25.杨晓英.丙种球蛋白治疗成人难治性特发性血小板减少性紫癜32例.广东医学院学报.2002,20(4):304-304
    26.郑立、袁颖、姜伟.静注中剂量丙种球蛋白治疗重症特发性血小板减少性紫癜9例疗效观察.川北医学院学报.2003,2(18):46-47
    27.邓颖仁.大剂量静滴丙种球蛋白治疗特发性血小板减少性紫癜近期疗效观察.临床医药实践杂志.2004,13(3):229-230
    28.凌历、孟秋、张志南.丙种球蛋白静注治疗重症特发性血小板减少性紫癜.黑龙江医学.2005,1(29):55-55
    29.王春森,王晓冬,张晋林.不同剂量丙种球蛋白治疗老年人重症特发性血小板减少性紫癜的近期疗效观察.四川医学.2006,27(2):151-152
    30.冯永旗.静注人血丙种球蛋白治疗儿童特发性血小板减少性紫癜疗效观察.实用医学杂志.2007,23(7):1049-1050
    31.应敏洁、徐进.两种剂量静注丙种球蛋白治疗特发性血小板减少性紫癜疗效分析.浙江临床医学.2008,10(1):60-60
    32.乔爱国,何思春,杨丽华.根除幽门螺杆菌治疗慢性特发性血小板减少性紫癜的临床探讨.第三军医大学学报.2007,29(14):1450-1451
    33.么露妍.慢性特发性血小板减少性紫癜和幽门螺杆菌感染的临床分析.吉林大学临床医学2007硕士论文
    34.李慧、刘霆,孟文彤.幽门螺旋杆菌感染与慢性特发性血小板减少性紫癜发病的临床研究.血栓和止血学.2006,12(4):160-162
    35.李红华,达万明.抗幽门螺杆菌治疗对慢性特发性血小板减少性紫癜患者疗效观察.中国实用内科杂志.2005,25(10):909-910
    36.陈登科,李沁.慢性特发性血小板减少性紫癜与抗幽门螺杆菌治疗关系的临床观察. 贵州医学杂志.2006,30(11):1024-1025
    37.许改香,钱文斌.美罗华和脾切除治疗难治性特发性血小板减少性紫癜1例.浙江医学.2005,27(8):618-618
    38.温艳,赖洵,沈晓梅.美罗华治疗原发性学小板减少性紫癜1例.中国误诊学杂志.2006,6(9):1813-1318
    39.邹农,华宝来,王书杰.利妥昔单抗治疗难治性特发性血小板减少性紫癜一例.中华医学杂志.2005,85(6):432-432
    40.赵永强,王庆余,瞿明.重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床研究.中华内科杂志.2004,43(8):608-610
    41.吴秋玲、何静、陈燕.重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的临床研究.华中科技大学学报(医学版).2004,33(3):297-299
    42.郭瑞官,李依秀,李健.大剂量维生素C治疗小儿慢性特发性血小板减少性紫癜25例报告.福建医药杂志.1994,16(2):12-13
    43.韩红玉,魏利惠,任玉英.大剂量维生素C治疗慢性原发性血小板减少性紫癜14例临床观察.山西职工医学院学报.1995,5(2):29-29
    44.王兆阳,许月琴.大剂量维生素C联合泼尼松治疗特发性血小板减少性紫癜疗效观察.临床研讨.1998,7(12):45-46
    45.孙玲,孙慧,陈绍倩,等.大剂量维生素C治疗难治性特发性血小板减少性紫癜14例.郑州大学学报.2003,38(6):983-983
    46.藤占庆.注射用维生素C治疗血小板减少性紫癜疗效观察.药物与临床.2006,14(3):222-223.
    47.杨光,夏国强,梁红.脾栓塞治疗难治性、免疫性血小板减少性紫癜.哈尔滨医科大学报.1997,2:177-178
    48.宋节,王军业,李晓明.部分脾栓塞治疗难治性血小板减少性紫癜.山东医药.1999,39(10):37-37
    49.张文娟,常靖,郑雪梅.脾动脉栓塞治疗慢性特发性血小板减少性紫癜临床疗效分析.实用医技杂志.2007,14(4):443-444
    50.Busto MJ,Llamas P,Cabrera R,et al.Pulsed high-dose dexamethasone in the treatment of refractory immune thrombocytopenia.Br J Haematol.1996 Jun;93(3):738-739
    51.Altintop L,Albayrak D.Oral high-dose methylprednisolone and intravenous immunoglobulin treatments in adult chronic idiopathic thrombocytopenic purpura.Am J Hematol.1997 Nov;56(3):191-192
    52.Van Riet FA,Wessels G,Hesseling PB.Experience with high dose dexamethasone in the treatment of chronic symptomatic immune thrombocytopaenia.East Afr Med J.1999Oct;76(10):571-574
    53.Gutierrez-Espindola GR,Morales-Polanco MR,Guerrero-Rivera S,et al.High doses of dexamethasone in adult patients with idiopathic thrombocytopenic purpura.Arch Med Res.2003 Jan-Feb;34(1):31-34
    54. Cheng Y, Wong RS, Soo YO, et al. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-836
    55. Borst F, Keuning JJ, van Hulsteijn H, et al. High-dose dexamethasone as a first-and second-line treatment of idiopathic thrombocytopenic purpura in adults. Ann Hematol. 2004 Dec;83(12):764-768
    56. Calabresi AR, Veith RW, Rigby PGHigh-dose cycles of dexamethasone in idiopathic thrombocytopenic purpura. J La State Med Soc. 2004 Sep-Oct;156(5):269-272
    57. Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-1407
    58. Moskowitz IP, Gaynon PS, Shahidi NT, et al. Low-dose cyclosporin A therapy in children with refractory immune thrombocytopenic purpura. J Pediatr Hematol Oncol. 1999 Jan-Feb;21(1):77-79
    59. Kappers-Klunne MC, van't Veer MB. Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001 Jul;114(1):121-125
    60. Emilia G, Morselli M, Luppi M, et al. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002 Feb 15;99(4): 1482-1485
    61. Perrotta S, Amendola G, Locatelli F, et al. Treatment with short-term, high-dose cyclosporin A in children with refractory chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2003 Apr;121(1):143-147
    62. Zver S, Zupan IP, Cernelc P. Cyclosporin A as an immunosuppressive treatment modality for patients with refractory autoimmune thrombocytopenic purpura after splenectomy failure. Int J Hematol. 2006 Apr;83(3):238-242
    63. F Cervantes, E Montserrat, C Rozman, et al. Low-dose vinCRistine in the treatment of corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) in non-splenectomized patients. Postgrad. Med. J. 1980, 56: 711-714
    64. Sikorska A, Slomkowski M, MarlankaK, et al. The use of vinca. alkaloids in adult patients with refractory chronic idiopathic thrombocytopenia. Clin Lab Haematol. 2004 Dec;26(6):407-11
    65. Shvidel L, Sigler E, Shtalrid M, et al. Vincristine-loaded platelet infusion for treatment of refractory autoimmune hemolytic anemia and chronic immune thrombocytopenia: rethinking old cures. Am J Hematol. 2006 Jun;81(6):423-425
    66. Szczepanik AB. The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients. Int J Lab Hematol. 2007 Oct;29(5):347-351
    67. Dickerhoff R, von Ruecker A. The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment. J Pediatr. 2000 Nov;137(5):629-632
    68. Choi CW, Kim BS, Seo JH, et al. Response to high-dose intravenous immune globulin as a valuable factor predicting the effect of splenectomy in chronic idiopathic thrombocytopenic purpura patients. Am J Hematol. 2001 Mar;66(3): 197-202
    69. Benesch M, Kerbl R, Lackner H, et al. Low-dose versus high-dose immunoglobulin for primary treatment of acute immune thrombocytopenic purpura in children: results of a prospective , randomized single-center trial. J Pediatr Hematol Oncol. 2003 Oct;25(10):797-800
    70. Peterlana D, Puccetti A, Simeoni S, et al. Efficacy of intravenous immunoglobulin in chronic idiopathic pericarditis: report of four cases. Clin Rheumatol. 2005 Feb;24(1): 18-21
    71. Ou CY, Hsieh KS, Chiou YH, et al. A comparative study of initial use of intravenous immunoglobulin and prednisolone treatments in childhood idiopathic. Acta Paediatr Taiwa. 2006 Sep-Oct;47(5):226-231
    72. Spahr JE, Rodgers GM. Treatment of immune-mediated thrombocytopenia purpura with concurrent intravenous immunoglobulin and platelet transfusion: A retrospective review of 40 patients. Am J Hematol. 2008 Feb;83(2):122-125
    73. Jarque I, Andreu R, Llopis I, et al. Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2001 Dec; 115(4): 1002-1003
    74. Kohda K, Kuga T, Kogawa K, et al. Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura. Br J Haematol. 2002 Aug;118(2):584-548
    75. Hashino S, Mori A, Suzuki S, et al. Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori. Int J Hematol. 2003 Feb;77(2):188-191
    76. Kohda K, Niitsu Y. Helicobacter pylori infection and idiopathic thrombocytopenic purpura. Nippon Rinsho. 2003 Apr;61(4):644-649
    77. Ando T, Tsuzuki T, Mizuno T, et al. Characteristics of Helicobacter pylori-induced gastritis and the effect of H. pylori eradication in patients with chronic idiopathic thrombocytopenic purpura. Helicobacter. 2004 Oct;9(5):443-452
    78. Suvajdzic N, Stankovic B, Artiko V, et al. Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura. Platelets. 2006 Jun;17(4):227-230
    79. Emilia G, Luppi M, Zucchini P, et al. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood. 2007 Dec 1;110(12):3833-3834
    80. Satake M, Nishikawa J, Fukagawa Y, et al. The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura. Jgastroenterol Hepatol. 2007 Dec;22(12):2233-2237
    81. Bisogno G, Errigo G, Rossetti F, et al. The role of Helicobacter pylori in children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008 Jan;30(1):53-57
    82. Rostami N, Keshtkar-Jahromi M, Rahnavardi M, et al. Effect of eradication of Helicobacter pylori on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura: A controlled trial. Am J Hematol. 2008 Jan 8 [Epub ahead of print]
    83. Vianelli N, Gugliotta L, Gianni L, et al. Ascorbic acid for the treatment of chronic refractory idiopathic thrombocytopenic purpura (ITP). Haematologica. 1992 Jan-Feb;77(1):92-93
    84. Karduss Urueta A, Morales Polanco MR, Pizzuto Chavez J, et al. Results of the treatment of chronic idiopathic thrombocytopenic purpura with ascorbic acid. Gac Med Mex. 1993 Jan-Feb;129(1):23-25
    85. Hirano A, Ueoka H. Successful treatment of an elderly patient with idiopathic thrombocytopenic purpura accompanied with chronic subdural hematoma, using a Chinese herbal medicine. EK-49, and ascorbic acid. Nippon Ronen Igakkai Zasshi. 2001 Mar;38(2):224-228
    86. Perotta. Rituxin in zhe treatment of chronic idiopathic thrombocytopenic purpura. Blood. 1999, 94: 49a
    87. Stsi R, Pagano A, Stipa. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001, 114: 121-125
    88. Delgado J, Bustos JG Anti-CD20 monoclonal antibody therapy in refratory immune thrmbocytopenic purpura. Haematologica. 2002, 87:215-216
    89. Stasi R, Stipa E, Forte V, et al. Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura. Blood. 2002, 99: 3872-3873
    90. Perrotta AL. Re-treatment of chronic idiopathic thrombocytopenic purpura with rituximab: literature review. Clin Appl Thromb Hemost. 2006 Jan;12(1):97-100
    91. Schweizer C, Reu FJ, Ho AD, et al. Low rate of long-lasting remissions after successful treatment of immune thrombocytopenic purpura with rituximab. Ann Hematol. 2007, 86(10):711-717
    92. Garcia-Chavez J, Majluf-Cruz A, Montiel-Cervantes L, et al. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis. Ann Hematol. 2007, 86(12):871-877
    93. Pasa S. he efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura. J Thromb Thrombolysis. 2008 Mar 3 [Epub ahead of print]