免疫性血小板减少性紫癜分型施治的基础与临床研究进展

免疫性血小板减少性紫癜(ITP)的发病涉及血小板免疫性破坏增多和骨髓巨核细胞产生血小板过少两个方面。经典的ITP治疗只涉及抑制血小板免疫破坏的一个方面,即采用免疫抑制剂如糖皮质激素、免疫球蛋白和抗-D抗体(针对Rh系统D抗原的抗体),也有采用长春新碱或抗人CD20单克隆抗体清除B淋巴细胞,以及环孢菌素等免疫抑制剂等。对难治性病例还要进行脾脏切除手术。虽然免疫抑制治疗方案对大多数患者治疗有效,但30%以上的ITP患者会复发,且这类治疗不良反应较多,脾脏切除还会导致机体免疫力下降,容易出现感染等并发症。临床需要更加安全有效的治疗方法。重组人血小板生成素(TPO)由于自身抗体而继发严重的血小板,目前已退出ITP的治疗。最近,欧洲批准了2个血小板受体激活剂AMG 531和Eltrombopag,通过促进巨核细胞分化和血小板生成来治疗ITP。国内采用泛细胞保护剂为主的联合方案治疗难治/复发性ITP也取得了良好的效果。总之,根据ITP患者不同的发病机理进行个体化治疗是未来ITP基础与临床的研究方向。本文就ITP的发病机理和临床治疗作一综述,并对ITP分型施治的可能性进行了初步的探讨。     

利福平致免疫性血小板减少性紫癜2例

病例报告例　1　男,31岁。1年前当地确诊左侧渗出性结核性胸膜炎,抗结核治疗半年(具体不详)后痊愈。1周前无明显诱因出现乏力,自以为胸膜炎复发而口服利福平0.6g/d,乏力不见好转。2天前口腔粘膜出现血疱破溃后出血不止伴全身皮肤紫斑,无发热、骨痛、血尿、黑便。无其他用药史及放射线接触史。查体:体温36.4℃,脉搏64次/分,呼吸16次/分,血压20.0/10.9kPa。皮肤散在大小不等新鲜瘀斑、瘀点,最大3cm×4cm。口腔粘膜数个血疱,部分溃破结痂,牙龈少量渗血,鼻腔内陈旧性血痂。浅表淋巴结不大。胸骨无压痛,两肺心脏未见异常。腹平软、肝、脾未触及…     

新生儿同族免疫性血小板减少性紫癜的临床研究

选择接受诊治的48例同族免疫性血小板减少性紫癜患儿,应用计算机平均分组,对照组接受泼尼松冲击治疗;观察组接受地塞米松冲击治疗。观察组总有效率为91.67%(22/24)远大于对照组的70.83%(17/24),差异有统计学意义(P<0.05)。观察组PAIg G、PAIg M、PAIg A等血小板相关抗体水平明显低于对照组,差异有统计学意义(P<0.05)。新生儿同族免疫性血小板减少性紫癜比较少见,临床应及时、准确做出诊断,积极进行有效治疗处理。     

免疫性血小板减少性紫癜动物模型的研究进展

免疫性血小板减少性紫癜（immune thrombocytopenic purpura,ITP）是一种较为常见的自身免疫病,其临床试验多建立于临床药物的应用,而非亚临床研究,有可能因为意外并发症被迫中止,因此建立理想的动物模型有助于加深对ITP发病机制和用药机理的理解.本综述回顾了ITP模型的发展过程,总结了被动型和主动型造模方法在ITP研究中的应用,尤其是转基因小鼠可更好模拟人类疾病病理状态,有利于进一步探讨新的诊断和治疗方法.     

重组人血小板生成素治疗老年慢性免疫性血小板减少性紫癜的疗效观察

目的:评价重组人血小板生成素(recombinant humanized thrombopoietin,rhTPO)治疗老年慢性免疫性血小板减少性紫癜(immune thrombocytopenia,ITP)的临床疗效和不良反应.方法:对2008年1月-2012年12月收治的25例慢性ITP老年患者,皮下注射rhTPO 300 U/(kg·d),每天1次,共14 d或至血小板计数≥100×109/L时,停止给药.停药后继续观察14d.依据成人ITP诊治中国专家共识(修订版)的标准进行临床疗效和安全性分析和评估.结果:经rhTPO治疗后,完全反应7例,有效13例,总有效率为80.0 ％(20/25).用药后血小板计数最高值平均达到(146.18±83.96)×109/L,停药后血小板计数缓慢下降,治疗后第28天血小板计数回落至(85.40±39.53)×109/L,均显著高于治疗前的血小板计数(15.30±7.97)×109/L(P＜0.01),但白细胞计数和血红蛋白含量在治疗前后差异无统计学意义(P＞0.05).rhTPO对凝血酶原时间、活化的部分凝血活酶时间和纤维蛋白原无显著影响(P＞0.05).治疗过程中出现的不良反应主要有嗜睡、头晕和乏力,分别为4例、3例、3例,腹泻和皮疹各1例.结论:rhTPO是治疗老年慢性ITP有效而且耐受性较好的治疗药物.     

免疫性药物性血小板减少性紫癜12例

免疫性药物性血小板减少性紫癜常以突发出血为临床表现，并且常出血现象严重，造成临床诊断棘手，我科近五年来收治12例病人，现报告如下：     

免疫性血小板减少性紫癜发病的免疫机制

免疫性血小板减少性紫癜(immune thrombocytopenic purpura,ITP)是一种器官特异性自身免疫性疾病,以免疫介导的血小板减少为特征.临床表现主要为外周血血小板计数减少,皮肤、黏膜或内脏出血.机体免疫功能紊乱是ITP发病的主要原因.本文主要对从免疫细胞亚群、血小板抗体、细胞因子等免疫因素来对ITP发病的免疫机制的进展作一综述.     

血浆置换治疗特发性免疫性血小板减少性紫癜1例

应用COBE—Spectra—TM血细胞分离机，通过治疗性血浆置换术(therapeutic压计plasma exchange，TPE)治疗l例特发性免疫性血小板减少性紫癜(idiopathic thrombocy—topenicpurpure，ITP)患者，取得良好效果，现报告如下。     

大剂量地塞米松治疗初诊免疫性血小板减少性紫癜的疗效观察

目的：观察大剂量地塞米松、常规剂量泼尼松两种方案治疗初诊免疫性血小板减少性紫癜（ITP）的临床疗效和不良反应.方法：45例初诊ITP分为两组,治疗组20例,地塞米松40 mg/d,静脉滴注,连用4d;对照组25例,泼尼松1 mg·kg^-1 ·d^-1,晨起顿服,3～4周后若血小板稳定,则开始减量,减量至10 mg/d时维持治疗4～6个月.结果：治疗后第4天治疗组与对照组血小板计数值为（35±18.2）×10^9/L和（16 ±6.4）×10^9/L,两组比较差异有统计学意义（P＜0.05）;治疗组和对照组总有效率分别为85％和76％,两组差异无统计学意义（P＞0.05）;长期反应率分别为52.6％和31.8％,两组比较差异有统计学意义（P＜0.05）;对照组所有病例皆出现不同程度类库欣氏表现;2例继发血糖升高;3例继发感染.治疗组不良反应较对照组明显减轻.结论：大剂量地塞米松治疗初诊ITP血小板上升速度快,长期反应率高,不良反应小,可作为临床一线方案.     

Management of patients with refractory immune thrombocytopenic purpura

In immune thrombocytopenic purpura (ITP), thrombocytopenia is a result of both increased platelet destruction and insufficient platelet production. In adults, the course is commonly chronic, but most patients never experience serious bleeding even with severe thrombocytopenia. In case series of consecutive adult patients identified at the time of diagnosis, the frequency of death from bleeding is low, < 1%. The goal of treatment is only to prevent bleeding, not to correct the platelet count to normal. All current treatments are designed to diminish the increased platelet destruction, either by immunosuppression or splenectomy. The frequency of death from complications of treatment is similar to the frequency of death from bleeding. Perhaps because of increasing recognition of both the infrequent occurrence of serious bleeding and the risks of immunosuppressive treatment and splenectomy, data from case series across the past 30 years suggest a trend toward less therapy and fewer splenectomies among patients with ITP. However treatment is necessary for patients with severe and symptomatic thrombocytopenia. Splenectomy remains the most effective treatment for ITP, with two-thirds of patients achieving durable complete remissions. Immunosuppressive agents, including rituximab and combinations of agents, may be less effective than splenectomy in achieving complete remissions and the remissions may also be less durable. New agents for patients with ITP are currently in development that enhance platelet production, rather than diminish platelet destruction. In preliminary reports, these agents have been effective in maintaining safe platelet counts in patients with chronic ITP that was refractory to splenectomy and other treatments.     

Prospective evaluation of the immunobead assay for the diagnosis of adult chronic immune thrombocytopenic purpura (ITP)

Summary.  Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by antibody-induced platelet destruction. To better define the role of antigen-specific assays in adult chronic ITP, we prospectively measured platelet-associated autoantibody against either glycoprotein (GP) IIb/IIIa or GPIb/IX in 282 patients with chronic ITP and 289 patients with thrombocytopenia of other causes. We divided chronic ITP into four subgroups: presplenectomy, mild (platelet count >30 000 µL⁻¹ requiring no therapy), presplenectomy, severe (platelet count <30 000 µL⁻¹ requiring therapy but not splenectomy), postsplenectomy, remission (postsplenectomy partial or complete remission without further therapy) and postsplenectomy refractory (required therapy after splenectomy failure). Positive results: total ITP group, 55.4%; presplenectomy, mild, 31.1%; presplenectomy, severe, 42.6%; postsplenectomy, remission, 50.0%; and postsplenectomy, refractory, 87.8%. In addition, the degree of positivity increased with the severity of the patient's disease. The assay had a minimum specificity of 84.4% if clinical factors, consistent with immune thrombocytopenia, were not considered in patients with thrombocytopenia associated with other diseases. However, if clinical factors consistent with immune thrombocytopenia were considered and only patients with questionable immune thrombocytopenia and patients 'lost to follow-up' were included in the false-positive group the specificity was 93.1%. We conclude that the presence of immune thrombocytopenia is highly probable if the immunobead assay is positive and that antigen-specific assays are diagnostically useful in adult chronic ITP.     

艾曲泊帕治疗成人原发免疫性血小板减少症的近期疗效及不良反应的荟萃分析

目的 综合评价艾曲泊帕治疗成人原发免疫性血小板减少症（ITP）的近期疗效、出血好转情况与安全性。方法 检索2018年4月前pubmed,万方数据库,维普数据库,CNKI,中国生物医学文献数据库,纳入艾曲泊帕治疗成人ITP的随机对照研究或单臂研究。评价纳入研究的方法学质量并提取数据后,采用R软件的meta程序包对结果进行合并分析。结果 共纳入5个随机对照试验和2个单臂临床研究,包括633例成人ITP患者。艾曲泊帕治疗组总有效率68%,出血好转率65%,与安慰剂组比较,总有效率、出血好转率有明显差异,不良反应差异无统计学意义。结论 艾曲泊帕治疗成人ITP疗效确切,不良反应低,可作为成人ITP治疗的新选择。     

Four patients with both thrombotic thrombocytopenic purpura and autoimmune thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome and indications for plasma exchange

Autoimmune thrombocytopenic purpura (ATP) and thrombotic thrombocytopenic purpura (TTP) are each well recognized clinical syndromes which may appear as single episodes or may have chronic relapsing courses. We present four patients negative for human immunodeficiency virus (HIV) infection who appear to have both diagnoses with either concomitant or intermingled episodes, and we review seven additional patients reported in the literature with similar features. All four of our patients are female, two have underlying connective tissue disorders, and their ATP processes came to our attention because of incomplete response of the platelet count to plasma exchange therapy (PEX) during a TTP phase (Cases 1 and 2) or development of thrombocytopenia in the absence of microangiopathy on the background of prior typical TTP episodes (Cases 3 and 4). Recognition of the ATP diagnosis in each case resulted in discontinuation of PEX (Cases 1 and 2) or not instituting PEX (Cases 3 and 4). In each instance, a satisfactory rise in platelet count followed treatment for ATP. Based upon this experience, we conclude that some individuals may have a mixed immune thrombocytopenia syndrome; careful analysis of the mechanism of thrombocytopenia, especially in recurrent episodes and in patients who respond incompletely to PEX for TTP, is important when deciding whether to initiate or continue PEX, or to consider therapies appropriate for other mechanisms of thrombocytopenia.     

Coexistence of thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura in an Asian woman: a case report

A 33-year-old Chinese woman with a history of immune thrombocytopenic purpura presented with heavy menstrual bleeding. She was found to have thrombocytopenia, plasma ADAMTS13 activity of 0%, and positivity for the plasma ADAMTS13 inhibitor. She was diagnosed with the coexistence of thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura. The patient was treated by plasmapheresis, a glucocorticoid, and rituximab. Her platelet level returned to normal, and she was discharged 28 days after admission. The number of plasmapheresis sessions and the timing of rituximab administration may be the key aspects of management of patients with thrombotic thrombocytopenic purpura who have underlying immune dysfunction caused by diseases such as immune thrombocytopenic purpura.     

重组人血小板生成素治疗难治性特发性血小板减少性紫癜的循证评价

目的探讨重组人血小板生成素治疗难治性特发性血小板减少性紫癜的循证评价。方法采用循证医学和文献分析的评价方法,检索中国期刊全文数据库(CNKI)、美国全科医学文献数据库(MEDLINE)、中国生物文献数据库(CBM)、生物医药与药理学文献数据库(EMBASE)、循证医学数据库(COCHRANE),收集所有有关重组人血小板生成素治疗难治性特发性血小板减少性紫癜的研究文章。结果重组人血小板生成素治疗难治性特发性血小板减少性紫癜的文章共计9篇,其中以自身对照进行研究的文章6篇,以随机开放对照进行研究的文章3篇。经Jadad改良法评分,8篇文章<3分属于低质量文章,1篇文章>3分,为多中心且随机开放对照进行研究文章。以自身对照进行研究的6篇文章结果基本一致,重组人血小板生成素可以明显提高患者的血小板计数,且不良事件较少。以随机开放对照进行研究的3篇文章结果也基本一致,重组人血小板生成素联合达那唑用药治疗效果明显好于单独使用达那唑。达那唑单独用药也具有一定的临床疗效,可以大幅提高患者的血小板计数。结论目前现有的研究文章表明重组人血小板生成素治疗难治性特发性血小板减少性紫癜的临床疗效显著,不良事件较少,但也存在不足,缺乏大样本研究。     

Preliminary laboratory based diagnostic criteria for immune thrombocytopenic purpura: evaluation by multi-center prospective study

BACKGROUND: We proposed diagnostic criteria for immune thrombocytopenic purpura (ITP) by modifying the existing guidelines for diagnosis of ITP and by incorporating laboratory tests found useful for predicting its diagnosis, for example erythrocyte count, leukocyte count, anti-GPIIb/IIIa antibody-producing B cells, platelet-associated anti-GPIIb/IIIa antibodies, percentage of reticulated platelets, and plasma thrombopoietin. OBJECTIVE AND METHODS: To validate our criteria, we conducted a multi-center prospective study involving 112 patients with thrombocytopenia and a morphologically normal peripheral blood film at the first visit. Each patient underwent a physical examination, routine laboratory tests, and specialized tests for the anti-GPIIb/IIIa antibody response and platelet turnover. RESULTS: Ninety-one patients (81%) satisfied the proposed criteria at first visit. Clinical diagnosis was made by skilled hematologists > 6 months after the first visit; ITP was diagnosed in 88 patients and non-ITP disorders in 24. The proposed criteria had 98% sensitivity, 79% specificity, a 95% positive predictive value, and a 90% negative predictive value. A relatively low specificity appears to be attributed to a few patients who had both ITP and aplastic anemia or myelodysplastic syndrome. CONCLUSIONS: Our preliminary diagnostic criteria based on ITP-associated laboratory findings were useful for the differential diagnosis of ITP, but additional evaluations and modifications will be necessary to develop criteria that can be used routinely.     

联合化疗治疗成人慢性难治性特发性血小板减少性紫癜

目的评价小剂量联合化疗对难治性特发性血小板减少性紫癜(TIP)的疗效及安全性。方法回顾性分析应用小剂量联合化疗31例成人难治性TIP患者的临床资料,并进行长期随访。结果31例患者中13例(41.9%)完全缓解(血小板≥100×109/L);9例(29.0%)部分缓解(血小板>50×109/L);9例(29.0%)未缓解(血小板<50×109/L)。联合化疗有效率为71.0%。3例失访;在28例获得随访患者中12例(42.9%)完全缓解,7例(25.0%)部分缓解,9例(32.1%)未缓解,联合化疗有效率为67.9%。28例中有10例完全缓解和3例部分缓解的患者在未接受其他治疗的情况下到随访结束时仍持续缓解,其中4例持续缓解超过60个月,5例超过36个月,1例超过12个月,3例少于12个月(分别为3月、6月和9月)。在随访患者中,有4例在化疗数月后因持续的血小板减少而导致中枢和/或胃肠道出血而死亡。结论对于糖皮质激素和脾切除治疗无效的某些难治性TIP患者,小剂量联合化疗可能不失为一种有效的治疗方法。