特发性血小板减少性紫癜患者B淋巴细胞凋亡研究

目的探讨B淋巴细胞在特发性血小板减少性紫癜(ITP)发病机制中的作用。方法用流式细胞术检测ITP患者外周血B淋巴细胞表面Fas蛋白、FasL蛋白以及胞浆内抗凋亡蛋白bcl2的表达水平。结果ITP患者外周血中B淋巴细胞表面Fas和FasL蛋白表达与对照组相比无统计学意义,B淋巴细胞胞浆内bcl2的表达水平高于正常人(P<0.05)。结论B淋巴细胞凋亡受抑可能参与ITP自身免疫的发病机制。     

环孢素A治疗难治性特发性血小板减少性紫癜20例

目的观察环孢素A治疗难治性特发性血小板减少性紫癜（ITP）的临床疗效。方法选择符合诊断难治性ITP诊断标准的20例患者,给予环孢素A 3～4mg/kg.d,分2～3次口服,维持量泼尼松5～10mg/d,口服,联合治疗4个月,判定疗效。结果显效例5（25%）,良效8例（40%）,进步3例（15%）,无效例4（20%）,总有效率为80%。结论环孢素A治疗难治性ITP取得了良好的疗效,不良反应轻微,是一种安全有效的治疗方法。     

环孢素A长期营救性治疗难治性特发性血小板减少性紫癜

目前治疗特发性血小板减少性紫癜(ITP)的方法包括:应用激素,脾切除,免疫抑制剂(化疗药、静脉注射大剂量甲泼尼龙),静脉注射大剂量免疫球蛋白,及一些探讨中的治疗方法如蛋白A免疫吸附、α干扰素、肝素、他莫昔芬、联合化疗、单克隆抗体、自体干细胞移植和     

环孢素A治疗难治性特发性血小板减少性紫癜九例疗效观察

我们用环孢素Ａ（ＣｓＡ）治疗９例难治性特发性血小板减少性紫癜（ＩＴＰ），取得良好疗效。一、资料和方法１病例选择：９例患者均符合１９８６年１２月首届全国血栓与止血学术会议修订之诊断标准，其中男３例，女６例；年龄１９～６７岁，平均年龄３５６岁。治疗前...     

环孢素A治疗特发性血小板减少性紫癜2例

我科曾用环孢素A(CSA)治疗特发性血小板减少性紫癜(ITP)2例,现报道如下。例1,女,32岁,因牙龈、皮肤出血和月经增多2月余,于1988年10月入院。查血小板(plt)25×10~9/L。骨髓象:巨核细胞全片13只,未见产生血小板巨核细胞(产板巨)。PAIgG66.1ng/10~7plt。ANA(—),dsDNA(—)。诊断ITP,用泼尼松(pred)和达那唑(DNZ)治疗,出血症状好转,plt未上升。后因丙氨酸     

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

特发性血小板减少性紫癜(ITP)是临床常见的出血性疾病,泼尼松常作为治疗ITP的首选药物,约三分之二的患者有效,在减量或停药时易复发,长期维持治疗副反应发生率高。本研究应用大剂量地塞米松(Dex)治疗47例初诊ITP患者,观察Dex治疗慢性ITP的疗效和安全性。一、资料与方法1.对象:2     

小剂量环孢素治疗难治/复发性特发性血小板减少性紫癜30例

<正>特发性血小板减少性紫癜(ITP)是一种获得性出血性疾病,患者主要以外周血小板单系减少伴或不伴有出血症状为主要临床表现〔1〕。糖皮质激素等一线治疗对多数患者可产生较好的疗效,但仍约有20%⁴0%的患者表现为对各种治疗无反应,因此难治/复发性ITP是目前临床医师面临的严峻挑战。环孢素A(Cs A)是近年来应用于治疗各种免疫性疾病的新型免疫抑制剂,主要用于再生障碍性贫血的治疗,小剂量Cs A治疗     

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

我们分析了 1996年 1月～ 1999年 1月来我院用环孢素Ａ(ＣｓＡ)治疗的 14例难治性特发性血小板减少性紫癜 (ＲＩＴＰ)患者 ,现将治疗结果报道如下。一、资料和方法1 病例 :所有病例均为本院患者 ,经血象及骨髓象确诊 ,符合第一届全国血栓与出血学术会议拟定的ＩＴＰ诊断标准。 14例ＲＩＴＰ中 ,女 11例 ,男 3例 ,年龄 17～ 6 6岁 ,平均年龄 38.3岁。所有患者均应用泼尼松 (≥ 6 0ｍｇ/ｄ) ,服药超过半年 10例 ;4例曾加用长春新碱 2ｍｇ/ｄ ,每周 1次 ,静脉输注 ,共 2～ 4次 ,1例加口服环磷酰胺 10 0ｍｇ/ｄ ,共 2周 ,但效果仍不佳。全部患者…     

慢性特发性血小板减少性紫癜患者外周血CD+4淋巴细胞凋亡的检测及临床意义

采用流式细胞仪检测了 2 6例慢性特发性血小板减少性紫癜 ( CITP)患者 ( CITP组 )外周血中 CD 4 细胞的体外凋亡率 ,以 ELISA法检测其血小板相关抗体 ( PAIg)含量。结果显示 ,CITP组外周血 CD 4 细胞凋亡率显著高于正常对照组 ,P=0 .0 1,其中泼尼松难治组与有效组无显著差异 ;CITP组PAIg G含量显著高于对照组 ,P<0 .0 1;PAIg G含量与 CD 4 细胞体外凋亡率成正相关 ( r=0 .73)。认为体外 CD 4 细胞凋亡异常反映了体内此类细胞的活化 ,可能与 CITP的发病有关。     

慢性特发性血小板减少性紫癜患者外周血CD^＋4淋巴细胞凋亡的检测 …

采用流式细胞仪检测了２６例慢性特发性血小板性紫癜患者外周血中ＣＤ＾＋４细胞的体外凋亡率,以ＥＬＩＳＡ法检测其血小板相关抗体含量。结果显示,ＣＩＴＰ组外周血ＣＤ＾＋４细胞凋亡了率显著高于正常对照组,Ｐ＝０．０１,其中泼尼松难治组与有效组无显著差异;ＣＩＴＰ组ＰＡＩｇＧ含量显著高于对照组,Ｐ〈０．０１;ＰＡＩｇＧ含量与ＣＤ＾＋４细胞体外凋亡率成正相关。认为体外ＣＤ＾＋４细胞凋亡异常反映了体内此类细胞的     

Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura

The role of pulsed high-dose dexamethasone (DXM) in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) is still uncertain. Following an early report in which it was described as an effective and well-tolerated treatment with a sustained platelet response in 100% of cases, a number of subsequent studies have failed to confirm such favorable results. As all these studies were conducted on small numbers of patients, we investigated further the effectiveness and side effects of this therapeutic modality in a larger cohort. Thirty-two patients with chronic ITP were scheduled to receive six monthly courses of intravenous DXM at the dose of 40 mg/day for 4 consecutive days. All patients had ITP that had been resistant to between two and five different therapeutic regimens, including 9 patients who had already failed splenectomy. All patients had to be seen 2 weeks after each cycle to asses their response as well as secondary effects. Three patients failed to respond and clinically required other therapy. Thirteen patients (41%) had a partial (platelet count between 50 and 100 x 10(9)/liter) or complete (platelet count >100 x 10(9)/liter) response to treatment, responses being mostly transient. Responses were observed early during the course of treatment, usually right after the first cycle of DXM. There were no late responses. Side effects were mild and did not require discontinuation of treatment. No clinical or laboratory parameter was found to predict treatment outcome. We conclude that high-dose DXM has a limited effect in patients with chronic ITP. Novel approaches and controlled multicenter trials may help identify new therapeutic strategies for this disease.     

抗CD20抗体治疗慢性特发性血小板减少性紫癜机制的研究

目的:通过抗CD20抗体(Rituximab,商品名:美罗华)与慢性特发性血小板减少性紫癜(cITP)骨髓体外培养,了解cITP患者B细胞的活化与凋亡的状况。方法:选择cITP患者30 例,对照组缺铁性贫血患者10例,进行骨髓体外培养,于培养前、培养3 d、培养6 d、培养9 d,检测B细胞相关分子(CD19、CD20、CD23)和透射电镜观测淋巴细胞凋亡状态。结果:cITP患者骨髓CD20、CD23分子表达显著高于对照组CD20、CD23分子表达(P<0.01)。加抗CD20抗体和加半量抗CD20抗体培养前后B细胞相关分子(CD19、CD20、CD23)检测结果差异有统计学意义(P<0.01)。加抗CD20抗体组透射电镜观测有淋巴细胞凋亡。结论:抗CD20 抗体能靶向性地与表达CD20抗原的B细胞结合,通过抗体抗原反应,诱导B细胞加速凋亡。     

High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults

The current first-line choice of treatment of idiopathic thrombocytopenic purpura (ITP) in adults, prednisone, is effective but has many side effects. Furthermore, reduction of the dose leads to a relapse of ITP in a majority of cases. Courses of high-dose dexamethasone (HD) aim to avoid these problems. We treated 36 patients with newly diagnosed or recurrent ITP with an 8-day course of HD, with a peak dose of 40 mg/day. The courses were repeated up to a maximum of six courses, with a 28-day interval. Acute and chronic effects of HD on platelet counts were observed, as well as side effects. HD led to an acute response (rise of platelet count to a level above 50×10⁹/l) in 83%. When HD was given as a first-line treatment, 59% of patients were still in remission after 31 months. When HD was given as a second-line treatment, 50% of patients were in remission after 5 months, declining to 25% after 54 months. Side effects were frequent but rarely dangerous. In conclusion, acute effects of HD were excellent. Long-term effects of HD as a first-line therapy of ITP were good, but its long-term effects as a second-line therapy were much poorer.     

High-dose intravenous IgG for chronic idiopathic thrombocytopenic purpura in adults

Summary Sixteen adult patients of mean age 48 years with chronic ITP were studied for platelet response to high-dose (0.4 g/kg body weight per day for five consecutive days) intravenous polyvalent intact IgG in the absence of any concurrent treatment. The platelet count returned to normal values in nine patients, a partial response (rise in the platelet count between 50 and 150 ×10⁹/l) was observed in three cases. One patient refractory to any other treatment went into a sustained remission. In the other responsive patients the response was only transient. Among seven splenectomised patients only three responded to IgG infusions versus nine in the non-splenectomised group. The length of ITP history appeared as a more critical factor for the response to IgG than previous splenectomy.     

胸腺肽α1联合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分析

目的探讨胸腺肽α1（Tα1）联合大剂量地塞米松（Dex）短程冲击治疗初治慢性特发性血小板减少性紫癜（ITP）的疗效及其细胞免疫机制。方法（1）66例初诊ITP患者口服Dex 40mg/d,连用4d;其中39例同时给予Tα1 1．6mg皮下注射,每周3次,连续应用4周。（2）ELISA法检测正常对照组20例及初诊ITP患者治疗前后血浆Tα1、IFNγ、IL-2、IL-4、IL-10及转化生长因子（TGF）-β1水平。结果（1）Tα1＋Dex联合治疗组与Dex单药治疗组,完全缓解（CR）率分别为76．9％（30／39）、44．4％（12／27）（P〈0．05）;长期反应率分别为61．5％（24／39）、34．6％（9／26）,复发率分别为38．5％（15／39）、65．4％（17／26）,差异均有统计学意义（P〈0．05）。（2）Tα1＋Dex治疗后Tα1水平为（1．83±1．22）μg/L较治疗前（2．43±1．47）μg／L明显降低（P〈0．05）。（3）Tα1＋Dex治疗后患者IFNγ和IL-2的血浆水平[（11．57±4．33）、（14．56±10．76）]ng／L均较治疗前[（22．71±7．98）、（28．42±11．27）]ng／L显著降低（P〈0．01）,且与正常对照组比较[（10．23±3．97）、（8．73±8．22）]ng／L,差异无统计学意义（P〉0．05）。IL-4和IL-10的血浆水平[（9．87±4．82）、（7．90±2．71）]ng／L均较治疗前[（5．93±3．85）、（3．24±1．36）]ng／L明显升高（P〈0．05）,且与正常对照组比较,差异无统计学意义（P〉0．05）。（4）Tα1＋Dex治疗后患者血浆TGF-β1水平（4．19±1．80）μg/L较治疗前（1．31±0．71）μg／L明显升高（P〈0．01）。（5）Tα1＋Dex治疗后患者Tα1水平与TGF-β1含量之间呈显著正相关（r=0．6028,P〈0．05）。结论（1）Tα1＋Dex联合治疗可以纠正ITP患者体内Th1／Th2平衡紊乱,减少血小板破坏,其CR率高、复发率较低且耐受性好,可作为ITP治疗的一种新的尝试。（2）Tα1＋Dex治疗后患者Tα1水平与作为Th3特异性标志的TGF-β1之间呈显著正相关,可能与NK细胞的生理性抑制功能上调有关。     

T-bet、GATA-3在慢性特发性血小板减少性紫癜患者外周血中的表达及意义

目的进一步探讨慢性特发性血小板减少性紫癜（CITP）的发病机制。方法选择25例CITP患者（CITP组）及25例健康体检者（正常对照组）,采用ELISA法检测外周血Th细胞因子IFN-γ、IL-10表达;采用RT—PCR检测外周血淋巴细胞中转录因子T-bet、GATA-3mRNA表达。结果与正常对照组相比,CITP组IFN—γ表达显著升高、IL-10表达显著降低（P〈0．01）,T—betmRNA表达明显升高、GATA-3mRNA表达明显下降（P〈0．05）。结论T-bet、GATA-3表达异常在CITP发生、发展过程中发挥重要作用,可能机制为增强TM细胞功能、抑制Th2细胞功能。     

Investigation of megakaryocyte apoptosis in children with acute and chronic idiopathic thrombocytopenic purpura

OBJECTIVE: Although the platelet destruction shows a primary role in the thrombocytopenia of idiopathic thrombocytopenic purpura (ITP), it has been demonstrated that impaired platelet production may also contribute to the severity of thrombocytopenia in ITP. The present study examined megakaryocyte apoptosis in bone marrow aspirates of children with acute and chronic ITP and investigated the role of megakaryocyte apoptosis in ITP pathophysiology. METHODS: Thirteen children diagnosed with acute ITP and eight children diagnosed with chronic ITP comprised the study group. Ten children, who were hospitalized for scoliosis operation but healthy otherwise, comprised the control group. In all children, megakaryocytes were isolated from the same amount of bone marrow aspirate samples using MACS CD61 MicroBeads (Miltenyl Biotec, Auburn, CA, USA). Megakaryocyte apoptosis was studied with transferase-mediated d-UTP-bitin nick end-labeling method. RESULTS: Isolated megakaryocyte counts did not differ significantly between acute ITP, chronic ITP and control groups. The percentage of apoptotic megakaryocytes did not differ significantly between acute ITP group and control group and between chronic ITP group and control group. The percentage of apoptotic megakaryocytes in patients with chronic ITP was significantly lower than the patients with acute ITP. There was no correlation between the percentage of apoptotic megakaryocytes and platelet counts of the cases. CONCLUSIONS: Increased megakaryocytic apoptosis does not play a role in the pathogenesis of dysmegakaryopoiesis and impaired platelet production in children with ITP. Decreased megakaryocyte apoptosis in cases with chronic ITP may be due to suppression of megakaryocyte maturation, as the terminal phase of the megakaryocyte lifespan is characterized by the onset of apoptosis.     

High-dose dexamethasone therapy in chronic idiopathic thrombocytopenic purpura

 A high-dose pulse of dexamethasone has been described as a current option for the treatment of refractory idiopathic thrombocytopenic purpura (ITP), but the results are controversial. Here we describe the use of a high dose of dexamethasone (40 mg per day for 4 days every month) in 18 patients with chronic ITP. The median age of the patients was 42.5 years (range, 16–77 years); 13 were female and five male. The duration of the disease ranged from 5 to 480 months, and splenectomy was carried out in six of the 18 patients.The overall results obtained revealed a satisfactory response (platelet counts higher than 50×10⁹/l) in eight of the 18 patients. However, a long-term remisson was achieved in only three of the eight patients with a follow up of 7–16 months. We were not able to identify any clinical or laboratory prognostic parameters or previous treatment which would allow one to predict a successful outcome of this treatment. These results suggest that a high dose of dexamethasone may provide an alternative, be it a poor one, for the treatment of refractory IPT, in which the use of a low-cost drug with limited side effects is an important consideration. Received: 18 March 1996 / Accepted: 2 July 1996     

Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura

The prevalence of Helicobacter pylori infection and the effect of its eradication on platelet count in 48 Japanese patients with autoimmune thrombocytopenic purpura (AITP), including 40 chronic idiopathic thrombocytopenic purpura (ITP) and eight secondary AITP, were investigated. H. pylori infection was found in 25 ITP patients (62.5%) and in two secondary AITP (25%). H.pylori eradication was obtained in 19 of 19 infected ITP patients (100%), who were not in remission (platelets < 100 x 109/l) at the time of infection assessment. During follow-up (median 14.8 months), 12 of 19 H. pylori-eradicated patients (63.2%) showed a significant increase in platelet count accompanied by a significant decrease of platelet-associated immunoglobulin G (IgG). This response was maintained in all responding patients throughout the follow-up period. However, two infected patients with secondary AITP did not show platelet increase after eradication. The assessment of H. pylori infection and its eradication should be attempted in ITP as this approach could be an effective strategy, at least for some of these patients.