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.     

血小板生成素受体激动剂的临床应用及研究进展

血小板减少症为临床常见的疾病,可见于血液系统疾病与非血液系统疾病.随着对促血小板生成药物研究的深入,血小板生成素受体激动剂（TPORA）罗米司亭及艾曲泊帕的临床应用,可有效提高患者血小板计数,为治疗血小板减少症提供新的治疗方法.笔者拟就TPORA的作用机制、其在血液系统疾病及肝病相关的血小板减少症中的临床应用的进展进行综述.     

免疫性血小板减少症老年患者个体化治疗的研究进展

免疫性血小板减少症(ITP)是一种由体液免疫及细胞免疫异常共同介导的自身免疫性疾病,血小板破坏增多及生成减少共同参与其发病.既往普遍认为儿童及育龄期妇女为ITP的高发人群,但近年来相关文献报道,随着年龄的增长,ITP的发病率不断增高,年龄≥60岁的老年人已经成为新的ITP高发人群.由于ITP老年患者合并症多,对治疗反应及耐受性较年轻患者差,更易发生严重的出血症状,病死率增高.目前,针对ITP老年患者的经典治疗方法包括:糖皮质激素、静注人免疫球蛋白(IVIG)、脾切除术、免疫抑制剂等,但是约1/3的ITP老年患者接受治疗后,疾病仍迁延不愈.随着相关研究的深入,利妥昔单抗、血小板生成素受体激动剂(TPORA)罗米司亭与艾曲波帕、新型免疫抑制剂霉酚酸酯(MMF)等新药在治疗ITP老年患者中均显示出较好的疗效,然而根据ITP老年患者的具体情况对其实施个体化治疗变得越来越重要.笔者拟对ITP的个体化治疗方法及其最新研究进展,结合ITP老年患者这一特殊群体的具体情况进行综述.     

免疫性血小板减少症时检测血小板相关抗体及血小板膜糖蛋白的意义

为探讨血小板表面血小板相关抗体(血小板相关免疫球蛋白)及血小板膜糖蛋白在免疫性血小板减少症中的诊断及预后评价方面的应用价值,采用流式细胞术(FCM)测定了76例血小板减少症患者及30名正常人血小板表面血小板相关免疫球蛋白(PAIg)及血小板膜糖蛋白(CD41,CD61,GPⅡb/Ⅲa).结果发现,初治38例特发性血小板减少性紫癜(ITP)患者中血小板相关抗体(PAlgG、PAIgM、PAIA)在血小板表面阳性百分率均高于正常对照组(P＜0.001),血小板膜糖蛋白均低于正常对照组(P＜0.01);9例经激素治疗的ITP患者PAIgG,PAIgM,PAIgA与正常对照组相比差异无统计学意义(P＞0.05),血小板膜糖蛋白与正常对照组相比差异无统计学意义(P＞0.02);继发性血小板减少症患者(慢性再生障碍性贫血、白血病、SLE、Evans综合征、甲亢、乙肝后肝硬化脾功能亢进)血小板相关抗体在血小板表面阳性百分率均高于正常对照组(P＜0.001),血小板膜糖蛋白均低于正常对照组(P＜0.05);12例治疗有效患者治疗后血小板相关抗体较治疗前下降(P＜0.05),血小板膜糖蛋白上升,其差异有统计学意义(P＜0.01).结论FCM用于免疫性血小板减少症患者的血小板相关抗体及血小板膜糖蛋白检测,具有灵敏、快速、简便的特点,是适用于临床诊断的新方法,对免疫性血小板减少症的诊断及疗效观察有较好的实用价值.     

利妥昔单抗在成年人原发性免疫性血小板减少症中的应用进展

原发性免疫性血小板减少症(ITP)是临床上常见的出血性疾病,以抗体介导的血小板破坏及血小板生成不良为特征.原发性ITP的初始治疗方案包括:糖皮质激素及静脉输注丙种球蛋白,而脾切除术、利妥昔单抗、血小板生成素(TPO)受体激动剂等常被用于治疗难治性及慢性原发性ITP患者.笔者拟就利妥昔单抗在成年人原发性ITP中的临床应用及进展进行综述.     

血小板生成素受体激动剂在脐血移植中的应用

血小板生成素受体激动剂(TPORA)是一系列可以与血小板生成素(TPO)受体(c-mpD特异性结合并发挥作用的药物.而脐血移植(CBT)自开始应用于临床后,由于其具有来源丰富、获取方便、供者无风险、人类白细胞抗原(HLA)配型相合程度要求较低、移植物抗宿主病(GVHD)发生率低,并且程度轻等优点,现已广泛被应用于恶性血液病的治疗.笔者就TPORA的生物学特性及其应用于CBT的前景和风险作一总结.     

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。     

一种新的血小板特异性抗体检测方法对免疫性血小板减少症诊断价值的研究

目的 检测血小板减少患者血清中针对血小板糖蛋白的特异性抗体,评价其对免疫性血小板减少症的诊断价值.方法 采用商业化试剂盒PAKAUTO,用酶联免疫吸附法(ELISA)检测各种血小板减少患者的自身血小板抗GPⅡb/Ⅲa、GPⅠ b/Ⅸ、GPⅠa/Ⅱa特异性抗体.结果 在免疫性血小板减少症诊断中此方法敏感性为44.0％,特异性为95.7％,阳性预测值为98.0％,阴性预测值为26.2％.阳性患者中GPⅡb/Ⅲa抗体阳性率为87％,GP Ⅰ a/Ⅱa抗体阳性率为35％,GPⅠb/Ⅸ抗体阳性率为10％.检测时未用免疫抑制剂患者阳性率(58.5％)高于用药患者(26.9％),差异有统计学意义(P ＜0.01);PLT≤20×109/L患者阳性率(51.6％)高于PLT＞ 20×109/L患者(27.8％),差异有统计学意义(P＜0.01);继发免疫性血小板减少症患者阳性率(66.7％)高于原发免疫性血小板减少症患者(41.7％),差异有统计学意义(P＜0.05).结论 PAKAUTO检测特异性强,可有效区分免疫性和非免疫性血小板减少,在免疫性血小板减少症临床诊断中可推广应用.     

血小板参数在血小板减少症鉴别诊断中的价值探讨

目的 探讨血小板参数在鉴别骨髓性和非骨髓性血小板减少症中的作用.方法 使用Cell-Dyn3700血细胞分析仪检测血小板减少症(TP)76例、特发性(免疫性、原发性)血小板减少性紫癜(ITP)66例、继发性血小板减少性紫癜(STP)8例、获得性纯巨核细胞再生障碍性血小板减少性紫癜(AATP)8例、造血干细胞疾病(HSCD)(急性白血病、再生障碍性贫血、骨髓增生异常综合征)140例、健康体检者100例(对照组)的血小板计数(PLT)、平均血小板体积(MPV)、血小板压积(PCT)、血小板分布宽度(PDW).结果 ①与对照组相比,HSCD患者的MPV显著减少,PDW明显增加;STP患者MPV、PDW显著增大.②AATP患者MPV正常,PDW增大.③ITP组和TP组与对照组的MPV、PCT、PDW差异有统计学意义(均P＜0.01).④HSCD组与对照组、ITP组和TP组比较,MPV、PCT和PDW差异有统计学意义(均P＜0.01).⑤骨髓性TP组与非骨髓性TP组比较,其MPV和PDW均有统计学意义(均P＜0.01).⑥当ITP患者治疗有效时,PLT升高,其MPV和PDW下降.结论 通过观察MPV和PDW数值的升降,特别是MPV的变化可初步判断血小板减少是由骨髓病变(MPV＜参考值)还是由骨髓外病症(MPV＞参考值)所引起.另外,当ITP患者治疗有效时,可用PDW和MPV较早地(比PLT提前5 d)观察到疗效.血小板参数的动态观察有助于ITP的鉴别诊断、病情判断及疗效观察.     

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。     

血小板聚集体计数在真性和假性血小板减少鉴别中的应用

目的 探讨血小板聚集体计数在真性和乙二胺四乙酸(EDTA)依赖性假性血小板减少(EDTA-PTCP)鉴别中的意义.方法 通过血细胞分析仪(简称仪器法)分析65份EDTA抗凝PLT减少标本(包括15份EDTA-PTCP标本及50份随机抽取的真性血小板减少标本)和50份PLT正常标本的血小板聚集体计数.通过更换柠檬酸盐抗凝剂和人工镜枪法(简称人工法)对仪器法检测PLT减少的标本进行PLT和血小板形态学复核,并比较分析真性和假性血小板减少在常规EDTA抗凝和柠檬酸盐抗凝2种情况下血小板聚集体计数的异同.结果 65份仪器法检测PLT减少的标本,PLT平均为(48±11)×109/L.其中50份真性血小板减少标本仪器法PLT平均为(48±10)×109/L,血小板聚集体计数为86±15;人工法PLT平均为(46±11)×109/L,镜检未发现血小板聚集现象;PLT在仪器法和人工法间差异无统计学意义(t=-1.26,P0.05).另外15份EDTA-FIEP标本,EDTA抗凝后仪器法PLT平均为(48±12)×109/L,血小板聚集体计数明显升高,平均为840±184;人工法PLT减少不明显,但血小板聚集明显,因此未能得到人工法PLT结果;采用柠檬酸盐抗凝后,仪器法PLT和人工法PLT均较前明显升高,分别为(141±13)×109/L和(134±17)×109/L,差异无统计学意义(t=-1.29,P0.05);血小板聚集体计数较前明显减少,平均为75±12,EDTA抗凝法与之比较差异有统计学意义(t=-6.82,P<0.001);镜下未见血小板聚集现象.结论 血小板聚集体计数有望成为监测血小板聚集的有用的临床指标,可用于判断由于血小板聚集引起的血细胞分析仪计数的假性血小板减少.     

遗传性血小板疾病基因诊断的研究新进展

遗传性血小板疾病是一类少见而复杂的出血性疾病,包括血小板膜糖蛋白缺陷、血小板贮存颗粒缺乏、血小板信号转导异常和血小板凝血活性异常.近十余年来,随着分子生物学技术及基因诊断技术的发展,多种遗传性血小板疾病发病的分子机制已逐渐阐明,如灰色血小板综合征是由NBEAL2基因突变导致,血小板减少症2是由于ANKRD基因5'-非翻译区(UTR)突变所导致的,Scott综合征是由TMEM16F基因突变引起,而某些疾病的发生需同时存在2种基因变异.这些研究结果对于提高遗传性疾病的诊断与治疗具有重要的意义,并为血栓疾病的防治提供了新的方向.现就近几年遗传性血小板疾病基因诊断的研究新进展进行综述.     

抗P-selectin及血小板糖蛋白Ⅱb/Ⅲa抗体检测在特发性血小板减少性紫癜与原发性干燥综合征伴血小板减少鉴别诊断中的意义

目的：探讨抗P-选择素（P-selectin）及血小板糖蛋白Ⅱb/Ⅲa（GPⅡb/Ⅲa）抗体测定在鉴别特发性血小板减少性紫癜（ITP）和原发性干燥综合征（pSS）伴血小板减少鉴别诊断中的意义。方法采用ELISA法分别测定40例ITP患者,36例pSS伴血小板减少患者及40名正常人血浆中的抗P-selectin及GPⅡb/Ⅲa抗体。结果 pSS伴血小板减少组、ITP组抗P-selectin及GPⅡb/Ⅲa抗体水平及阳性率均高于正常对照组（P＜0.01）;pSS伴血小板减少组抗P-selectin抗体水平及阳性率显著高于ITP组（P＜0.01）;而pSS伴血小板减少组抗GPⅡb/Ⅲa抗体水平及阳性率与ITP组比较差异无统计学意义（P＞0.05）。结论抗P-selectin及GPⅡb/Ⅲa抗体测定在ITP和pSS伴血小板减少鉴别诊断中有显著的临床意义。     

Thrombocytopenia secondary to iron deficiency anemia responding to iron therapy

A broad spectrum of diseases can cause anemia and thrombocytopenia. Some of these diseases are a hematological emergency; others are benign diseases, so early and accurate diagnosis is crucial in managing such patients. Usually, IDA is associated with thrombocytosis or normal platelets; however, in rare cases, IDA can be associated with thrombocytopenia; even though, thrombocytopenia that occurs with IDA responds to iron therapy. Iron therapy rarely causes transient thrombocytopenia per se. We are reporting an African female patient who is found to have thrombocytopenia secondary to iron deficiency anemia (IDA), and she responded to iron replacement therapy initially with a transient drop in platelets, followed by a rapid rise in platelets till platelets reached the normal level.     

Thrombocytopenia during pregnancy. Importance, diagnosis and management

Thrombocytopenia is observed in 6 to 15% of pregnant women at the end of pregnancy, and is usually moderate. Gestational thrombocytopenia (defined as a mild thrombocytopenia, occurring during the 3 rd trimester with spontaneous resolution postpartum and no neonatal thrombocytopenia) is the most common cause of thrombocytopenia during pregnancy but a low platelet can also be associated with several diseases, either pregnancy specific or not, such as preeclampsia, HELLP syndrome, or idiopathic thrombocytopenic purpura (ITP). The differential diagnosis between ITP and gestational thrombocytopenia is clinically important with regard to the fetus, due to the risk of neonatal thrombocytopenia. However, this differential diagnosis is very difficult during pregnancy. Thrombocytopenia which need to be investigated are the following: thrombocytopenia known before pregnancy, thrombocytopenia occurring during the 1(st) and 2(nd) trimester, platelet count <75 G/l in the 3(rd) trimester or thrombocytopenia in case of pregnancy with complications. Investigations have to be discussed in function of history and clinical examination, gestational age and severity of thrombocytopenia. No treatment is required in case of gestational thrombocytopenia. There are few data to distinguish management of ITP between pregnant and non-pregnant women but management is different because of the potential adverse effects of the treatment for the woman and/or the fetus, the requirement for a good hemostasis at delivery and the risk of neonatal hemorrhage. One important problem is that it is not possible to predict the risk of neonatal thrombocytopenia in babies born from women with ITP.     

N‐glycan profiling alterations of serum and immunoglobulin G in immune thrombocytopenia

BackgroundThe glycosylation alterations of serum and IgG are involved in a variety of autoimmune and inflammatory diseases and have shown great potential in biomarker field. The diagnosis of immune thrombocytopenia (ITP) is exclusive. Our study aimed to discover the potential glyco‐biomarkers for auxiliary diagnosis of ITP.MethodsThe serum samples were obtained from 61 ITP patients and 35 healthy controls, and IgG samples were purified from 34 out of 61 ITP patients and 35 healthy controls. DNA sequencer‐assisted fluorophore‐assisted carbohydrate electrophoresis (DSA‐FACE) was used to analyze serum and IgG N‐glycan profiling.Results6 of 12 serum N‐glycan peaks, 6 of 7 IgG N‐glycan peaks, serum fucosylation, and IgG galactosylation were significantly different between ITP patients and healthy controls (p < 0.05). IgG peak 7 showed good diagnostic efficacy for discriminating ITP patients from healthy individuals (AUC 0.967). ITP patients with severe thrombocytopenia had a significantly lower serum fucosylation than ITP patients with mild and moderate thrombocytopenia (p < 0.05). Serum fucosylation and serum peak 5 were correlated with platelet counts in ITP patients with severe thrombocytopenia, and the absolute values of correlation coefficient were both over 0.5.ConclusionsThe specific N‐glycan patterns of serum and IgG were observed in ITP patients. IgG peak 7 was a potential biomarker for auxiliary diagnosis of ITP.     

Outcome of collagen vascular diseases by treatment with plasmapheresis.

The outcome of collagen vascular diseases after treatment with plasmapheresis was studied in 9 patients with polyarteritis nodosa (PN), in 2 patients with Wegener's granulomatosis (WG), in 1 patient with allergic granulomatous angitis (AGA), and in 20 patients with systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). Improvement after treatment with plasmapheresis was observed in 41.7% of the patients with PN, WG, and AGA. On the other hand, with the exception of 1 patient with thrombocytopenia and 1 patient with renal failure, all of the clinical manifestations, including thrombocytopenia, central nervous system (CNS) lupus, thrombophlebitis, lung infarction, and recurrent abortions in the SLE patients with APS, improved after plasmapheresis. Plasmapheresis is thought to be an influential strategy of treatment for patients with collagen vascular diseases.     

Advances in the studies on human platelet alloantigen--review]

Human platelet alloantigens (HPA) are specific antigens carried by platelet glycoproteins, which genes showing single nucleotide polymorphism. HPA can induce alloantibodies bringing about alloimmune response. They play important roles in post-transfusion refractoriness to platelets, post-transfusion thrombocytopenic purpura, fetomaternal alloimmune thrombocytopenia, and graft-versus-host disease. Because of their side effects in clinical blood-transfusion, there were a great deal of studies on HPA during last few decades. This review focuses on the nomenclature of HPA, the polymorphisms of platelet glycoproteins, HPA typing of the serological and molecular technology, as well as the mechanism of alloimmunization to HPA and correlated diseases.     

人类血小板同种抗原研究进展

人类血小板同种抗原（human platelet alloantigens, HPA）是由血小板糖蛋白携带的一类特异性抗原，其基因具有单核苷酸多态性（SNP）。HPA可介导同种抗体的产生，引起同种免疫反应，与输血后血小板减少性紫癜（PTP）、血小板输注无效（PTR），新生儿同种免疫血小板减少性紫癜（NAITP）及移植排斥密切相关。因其在临床输血实践及相关疾病中的重要作用，而备受关注。本文就HPA抗原的命名、血小板糖蛋白多态性、HPA检测方法、血小板同种免疫反应机制以及相关疾病研究进展作一综述。