以血小板减少为首发症状的结缔组织病与免疫性血小板减少性紫癜的鉴别诊断

目的通过对以血小板(platelet,PLT)减少为首发症状的结缔组织病(connective tissue disease,CTD)和免疫性血小板减少性紫癜(immune thrombocytopenic purpura,ITP)的实验室相关检测指标及治疗疗效的分析研究,寻求其鉴别诊断方法。方法收集我院2014年3月-2015年6月住院的18例以PLT减少为首发症状的CTD患者为CTD组和22例ITP患者为ITP组,对所有患者的实验室检测指标及临床治疗效果进行分析。结果 CTD组的血红蛋白、C3、C4显著低于ITP组,而PLT、血沉和Ig G均显著高于ITP组,差异均有统计学意义(P均0.05)。CTD组患者临床治疗的总有效率较高,为94.4%,其中单纯采用激素治疗及联合免疫抑制剂治疗的有效率(66.7%,16.7%)均高于ITP组患者(50.0%,13.6%),而采用丙种球蛋白/重组人血小板生成素治疗的有效率(11.1%)低于ITP组患者(18.2%)。结论以PLT减少为首发症状的CTD发病人群以中青年女性居多,ITP的发病人群年龄跨度较大。但这两种疾病的临床表现相似,故应结合实验室相关检测指标进行鉴别。对于临床表现不典型的CTD合并PLT减少患者,还需动态监测其自身抗体谱以进一步确诊,且确诊后建议及时应用激素联合免疫抑制剂治疗。     

成年人原发免疫性血小板减少症的二线治疗方案选择

原发免疫性血小板减少症(ITP)为以血小板数目减少为特征的自身免疫性疾病.近年来,成年人ITP在发病机制、诊断、治疗等方面均获得重大进展,尤其是利妥昔单抗、血小板生成素(TPO)及血小板生成素受体激动剂(TPORA)在临床成年人ITP治疗中的广泛应用,使成年人ITP二线治疗方案的选择不再局限于脾切除术.笔者主要探讨成年人ITP患者二线治疗方案的选择,为采取一线治疗方案治疗失败的ITP患者提供个体化治疗方案.     

老年人特发性血小板减少性紫癜 68例临床特点分析

特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)是一种免疫介导的以血小板减少为主要临床表现的自身免疫性疾病,是临床最为常见的出血性疾病之一.本病多发于儿童和育龄期妇女,近年来,作者在临床工作中观察到老年ITP患者并不少见,且老年ITP患者因其基础病较多,因而在临床表现、治疗效果等方面与年轻患者有所不同.作者自2000年1月至2010年1月对68例老年(≥60岁)ITP患者的临床特点、治疗方案、治疗反应进行分析,对处理老年ITP的经验进行报道.     

难治性特发性血小板减少性紫癜的治疗进展

特发性血小板减少性紫癜(简称ITP)是一种自身免疫性疾病。大多数患者在儿童期呈急性、自限性病程,预后良好。少数患者(15～30％)病程迁延,对激素、免疫抑制剂及脾切除等治疗均无显著疗效,这在临床上称为难治性(或顽固性)ITP。随着近年来对ITP的发病机理的深入研究,对难治性ITP的治疗也有了许多新进展,现概述如下。     

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。     

难治/复发性免疫性血小板减少症的治疗现状与进展

原发性免疫性血小板减少症(immune thrombocytopenia,ITP)是一种免疫介导的获得性血小板减少所致出血性疾病,其患者外周血小板计数＜100×109/L,并且没有引起血小板减少的明显诱因或基础疾病.目前难治性ITP的治疗十分棘手,尚无统一的治疗方案.抑制血小板过度破坏和促进血小板生成是现代ITP治疗的主流思路.其中,促血小板生成药物是近年来治疗难治性ITP的新方向.ITP的发病机制复杂且多样化,如何甄别ITP患者的发病机制并给予针对性的个体化治疗,将是今后关于ITP在临床与科研中的重要方向.     

根除幽门螺杆菌在原发免疫性血小板减少症中的应用进展

原发免疫性血小板减少症(ITP)是一种免疫介导的血小板过度破坏及生成减少所致的出血性疾病,其发病机制尚未完全阐明,临床治疗首选糖皮质激素,有效率约60%,然而部分难治性ITP患者应用激素治疗效果欠佳。近年来研究报道抗幽门螺杆菌(Hp)感染治疗对部分ITP患者有效,同时也有相关研究对之提出争议,关于Hp如何参与ITP发生的作用机制也尚未阐明,本文就Hp与ITP关系的临床研究进展作一综述。     

血浆置换治疗慢性ITP疗效观察及实验分析

原发性血小板减少性紫癜(ITP)临床上以激素、脾切除和免疫抑制剂治疗为主.笔者对10名慢性原发性血小板减少性紫癜(CITP)患者进行了血浆置换治疗,作为该病治疗的一种尝试和经验积累,现报道如下.     

促血小板生成制剂治疗慢性难治性特发性血小板减少性紫癜的发展概况

特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP),是一种自身抗体介导的血小板过度破坏引起的出血性疾病,因此,抑制血小板破坏成为治疗的主要手段.同样,对慢性难治性ITP的传统治疗方法,是用免疫抑制剂(如激素、环孢素)、免疫调节剂(球蛋白制剂、单克隆自身抗体)和去除破坏部位(切脾、脾放疗)等针对血小板破坏进行治疗的.近些年,随着对ITP发病机制的进一步研究,发现除血小板破坏外,血小板生成不足在ITP的发病中也起了重要作用[1].因此,作为慢性难治性ITP治疗的补充手段--促血小板生成制剂也一直足研究的热点,现对促血小板生成制剂的发展概况综述如下.     

免疫性血小板减少性紫癜的发病机制

免疫性血小板减少性紫癜(ITP)是一组以血小板减少为特征的自身免疫紊乱性疾病群.既往认为,ITP发病机制为经典体液免疫机制,即通过自身抗体作用于未成熟血小板,使其在单核巨噬系统被吞噬所致,并可影响巨核细胞和血小板的发育成熟.目前,细胞免疫在ITP发病机制中的作用越来越受到重视,血小板、巨核细胞的细胞凋亡异常对ITP发病有影响,而一些细胞亚群比例异常和细胞因子水平异常被证实存在于ITP患者中,有关ITP患者基因的相关研究也取得了一定进展.除此之外,神经轴突导向分子(Sema)5A与维生素D3的异常,也参与ITP的发病.笔者拟主要从体液免疫、细胞免疫、细胞凋亡、基因表达、氧化应激等方面,对ITP发病机制的最新研究进展进行阐述.     

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AMG531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。     

特发性血小板减少性紫癜的克隆性研究

特发性血小板减少性紫癜(ITP)患者的血小板糖蛋白上存在自身抗原表位，这些抗原表位定位于糖蛋白的某些特定区域，其数量有限。在部分慢性ITP患者中，存在B淋巴细胞和(或)T淋巴细胞的克隆性扩增，其自身抗体是克隆性起源的。这些研究对于探索特异性高、毒性小的靶向性治疗和揭示其发病机制具有重要意义。本综述讨论了ITP自身抗体的克隆限制性和B淋巴细胞的克隆性扩增，ITP中T淋巴细胞的克隆性和研究ITP克隆性的意义。     

原发免疫性血小板减少症的规范化诊治

原发免疫性血小板减少症(primary immune thrombocytopenia, ITP)是一种获得性免疫介导的血小板减少性疾病,其发病机制为免疫失耐受导致的血小板破坏过多及巨核细胞产生血小板不足。临床表现主要为血小板减少性的出血及疲劳等症状。ITP的诊断无特异性指标,需排除其他的血小板减少性疾病。治疗目的为维持血小板在安全水平,预防出血,并提高患者生活质量。治疗指征为血小板≤30×10⁹/L和(或)有出血表现,对于老年患者、重体力劳动者、有高血压等出血风险较高的合并症患者以及需抗血小板、抗凝治疗患者等,可适当放宽治疗指征。一线治疗为糖皮质激素及静脉注射人免疫球蛋白;二线治疗包括促血小板生成药物、利妥昔单抗及脾切除等治疗;对于难治性ITP患者,可考虑维A酸等三线治疗。     

A multicenter retrospective analysis on therapeutic plasma exchange in immune thrombocytopenic purpura

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia and skin and mucosal bleeding. In patients with an indication for treatment, corticosteroids, intravenous immunoglobulin (IVIg) and anti-D are recommended as the first line, while splenectomy, thrombopoietin receptor agonists or rituximab are recommended second line options. Approximately 10 % of adult patients with ITP fall into the chronic refractory ITP group. Therapeutic plasma exchange (TPE) has generally been tested in patients with refractory ITP, who have failed to respond to conventional treatments, in case of bleeding or prior to surgical interventions. It has been stated that elimination of the antibodies that are held responsible in the pathogenesis of the disease has an effective role in the treatment. In this article, we present the results of 17 patients, who underwent TPE for refractory ITP, together with the literature data.     

First-line therapies for immune thrombocytopenic purpura: re-evaluating the need to treat

Immune thrombocytopenic purpura (ITP) can be challenging to both diagnose and treat: despite the ability to detect anti-platelet antibodies, the diagnosis of ITP remains one of exclusion. Management of ITP is similarly difficult as many therapies pose potential risks that may be worse than the disease. It has been generally agreed that bleeding - not platelet count - should be the rationale for treatment. Despite the absence of prospective, controlled studies, there is consensus that bleeding risks are significantly greater in patients with platelet counts <20 x 10(9)-30 x 10(9)/L, and therefore treatment is indicated for these patients; for those with platelet counts that are higher, but still <50 x 10(9)/L, treatment is also indicated if accompanied by substantial mucous membrane bleeding. The standard initial treatment for ITP is oral corticosteroids to increase platelet counts. Intravenous immunoglobulin or anti-D immunoglobulin can also increase platelet counts and are particularly useful for stimulating rapid platelet increases before planned procedures. Splenectomy, which produces a long-lasting response in a majority of patients, is still commonly used for those who do not have long-term responses to steroid therapy and it should remain the gold standard therapy. However, splenectomy is an invasive procedure with some patients relapsing even after several years. Very rare cases of life-threatening or lethal infections may also occur at any time after splenectomy and thus physicians and patients are increasingly reluctant to advise or agree to this treatment approach. Other treatments have been evaluated to prevent or delay splenectomy, including high-dose dexamethasone, intermittent anti-D immunoglobulin infusions, and rituximab. There have been few randomized, placebo-controlled studies of these approaches, and they cannot currently be recommended as their efficacy and safety remain unclear. Thrombopoietin receptor agonists are currently under clinical investigation for the treatment of ITP and may represent an alternative treatment option in the future. The criteria for treating ITP and the benefits and risks of therapies are discussed here. Ongoing and future studies will help define the best strategies for increasing platelet counts and reducing the risk of bleeding in ITP patients.     

特发性血小板减少性紫癜患者外周血调节性T细胞的研究

目的研究特发性血小板减少性紫癜（ITP）患者外周血CD4^＋CD25^＋调节性T细胞（Tr细胞）的变化，探讨其在ITP发病机制中的作用。方法分别收集35例ITP患者及健康对照组外周抗凝静脉血，分离纯化T淋巴细胞。应用藻红蛋白（PE）标记的抗CD4单抗及异硫氰酸荧光素（FITC）标记的抗CD25单抗，作双色流式细胞术，分析ITP患者外周血CD4^＋CD25^＋调节性T细胞百分率。结果ITP组外周血中Tr细胞明显低于健康对照组（P〈0．05），Tr细胞占CD4^＋T细胞的比例也低于健康对照组（P〈0．05）。结论ITP患者外周血存在细胞免疫功能失调，Tr细胞数量减少可能与ITP的发病机制有关。     

Management of adult idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is defined as isolated thrombocytopenia without a clinically apparent cause. It is categorized as acute, chronic, and refractory. Its clinical presentation ranges from acute to insidious and the bleeding may vary from minimal to severe. The target platelet count with therapy is more than 30,000/microL in sedentary individuals. Since studies regarding therapies for ITP have been mostly uncontrolled case series, the treatment recommendations are largely derived from expert opinion. This review paper summarizes the data on available therapies for adult acute and chronic/refractory ITP. The therapies include splenectomy, steroids, intravenous immunoglobulin, anti-Rh(D), monoclonal antibodies, danazol, chemotherapy, plasma exchange, and others.     

Refractory idiopathic thrombocytopenic purpura

Chronic refractory idiopathic purpura(ITP) is defined as ITP with persistent thrombocytopenia despite conventional initial management with corticosteroids and splenectomy. The goal of treatment is not cure of the ITP, but only to achieve a safe platelet count, which is arbitrarily assumed to be greater than 30,000/mm3. The risk for major bleeding seems great only when the platelet count is less than 10,000/mm3. There is no accepted algorithm for management of patients with chronic refractory ITP. Recently, more targeted therapies including rituximab, anti-CD40 ligand and Campath-1H have been evaluated in refractory ITP.