血小板特异性抗体与ITP发病、临床特点、治疗及预后效果的关系

免疫性血小板减少症（immune thrombocytopenia,ITP）是一种自身免疫性出血性疾病。目前认为血小板自身抗体的形成是本病主要的发病机制之一,其一线治疗中激素和丙种球蛋白均主要通过抑制自身抗体产生、封闭网状内皮系统FC受体等作用以减少血小板的破坏,但有部分患者对一线治疗无效,病程迁延,预后不良,最终进展为慢性/难治性ITP（chronic/refractory ITP,C/RITP）。研究发现,血小板膜糖蛋白GPIIb/IIIa和GPIbα是本病最常见的抗原靶位,而一线治疗对具有抗GPIbα的ITP患者疗效欠佳。进一步研究发现抗GPIIb/IIIa抗体与抗GPIbα抗体导致血小板破坏的途径不尽相同：前者主要为依赖FC途径,而后者主要通过FC非依赖性途径清除血小板。以上研究结果提示早期发现ITP血小板抗体类型对于治疗和预后该疾病起关键作用。本文主要对ITP特异性血小板抗体与疾病的发生、临床特点、治疗及预后的关系进行综述。     

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。     

Autoimmune thrombocytopenia

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which platelets coated with mainly antibodies against platelet GPIIb/IIIa and GPIb/IX are destroyed in the spleen. Recent evidence suggests that platelets are also destroyed by cytotoxic T cells. The diagnosis is made by exclusion for other causes of thrombocytopenia. As routine blood counts are becoming more available, many mild cases of ITP (platelets >30 x 10(9) L(-1)) are being diagnosed and they usually do not require treatment. In patients with platelet counts persistently <30 x 10(9) L(-1), treatment with corticosteroids, and/or intravenous immunoglobulin (IVIG) or anti-D may be required. The primary goal of treatment is to maintain the platelet count at a safe level with minimal side effects. After 3-6 months, if spontaneous remission has not occurred and if the side effects are significant, splenectomy is recommended. This is the single most effective treatment of ITP. The refractory patients who fails splenectomy and subsequently first- and second-line therapies, is a management dilemma. Therapeutic options are limited, available treatments potentially toxic and the chances of sustained response low. Observation with no active treatment is a reasonable option. With the increased availability of the thrombopoietic agents in the future, there may be a good prospect of keeping the platelet counts of these refractory patients at a safe long-term level with one of these drugs.     

艾曲泊帕联合小剂量泼尼松治疗老年难治复发原发免疫性血小板减少症疗效观察

目的 观察艾曲泊帕联合小剂量泼尼松治疗老年难治复发原发免疫性血小板减少症(primary immune thrombocytopenia,ITP)的疗效。方法 采用回顾性研究方法,分析52例60岁以上老年难治复发ITP患者的疗效,其中艾曲泊帕联合小剂量泼尼松治疗组(艾曲泊帕治疗组)23例,泼尼松联合免疫制剂(常规治疗组)29例。观察两组治疗前及治疗后1、2、4、8、12周血小板计数;治疗前及治疗后2周出血评分;治疗后4、8、12周有效率。结果 治疗第1周艾曲波帕治疗组血小板计数开始升高,此后血小板持续升高,第4周血小板计数为(109.18±77.81)×10⁹/L,且每一个观察截点均较前一观察截点有明显升高,差异具有统计学意义(P<0.05);常规治疗组治疗后血小板升高,但无持续升高趋势。两组出血积分治疗后分别为(2.91±1.92)分、(3.60±2.53)分,较治疗前[(7.64±3.77)分、(6.53±3.66)分]均有明显下降(P<0.05)。第8、12周艾曲波帕治疗组总有效率分别为87%、91.3%,与常规治疗组(55.2%、55.2%)相...     

Contemporary management of primary immune thrombocytopenia in adults

Summary. Immune thrombocytopenia (ITP) comprises a syndrome of diverse disorders that have in common immune‐mediated thrombocytopenia, but that differ with respect to pathogenesis, natural history and response to therapy. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or as a sequela of a growing list of associated conditions (secondary ITP). Primary ITP remains a diagnosis of exclusion and must be differentiated from non‐autoimmune etiologies of thrombocytopenia and secondary causes of ITP. The traditional objective of management is to provide a hemostatic platelet count (> 20–30 × 10⁹ L^?1 in most cases) while minimizing treatment‐related toxicity, although treatment goals should be tailored to the individual patient and clinical setting. Corticosteroids, supplemented with either intravenous immune globulin G or anti‐Rh(D) as needed, are used as upfront therapy to stop bleeding and raise the platelet count acutely in patients with newly diagnosed or newly relapsed disease. Although most adults with primary ITP respond to first‐line therapy, the majority relapse after treatment is tapered and require a second‐line approach to maintain a hemostatic platelet count. Standard second‐line options include splenectomy, rituximab and the thrombopoietin receptor agonists, romiplostim and eltrombopag. Studies that directly compare the efficacy, safety and cost‐effectiveness of these approaches are lacking. In the absence of such data, we do not favor a single second‐line approach for all patients. Rather, we consider the pros and cons of each option with our patients and engage them in the decision‐making process.     

Th17细胞及与免疫相关性血液病关系的研究进展

Th17细胞是一种新发现的T细胞亚群,可特异性分泌IL-17。RORγt和STAT3是Th17细胞的特异性转录因子。近年来已发现,Th17细胞在多种自身免疫性疾病中比例增高且功能亢进。本文简要综述了Th17细胞及与再生障碍性贫血、自身免疫性溶血性贫血、免疫性血小板减少症和免疫相关性血细胞减少症几种免疫相关性血液病的发生及疾病严重程度之间的关系。     

A review of antiphospholipid antibody syndrome

PURPOSE: To review the pathophysiology, clinical presentation, and management options for antiphospholipid antibody syndrome (APS), a potentially life-threatening coagulation disorder. DATA SOURCES: Selected scientific literature, consensus guidelines, and expert opinion. CONCLUSIONS: Clinical features that should alert the clinician to consider APS include recurrent fetal loss, arterial or venous thrombosis, thrombocytopenia and livedo reticularis. One should be suspicious of this diagnosis in a younger patient, one with an autoimmune disease, or family history of autoimmune disease. To confirm the diagnosis one needs both clinical and laboratory abnormalities. IMPLICATIONS FOR PRACTICE: The signs and symptoms of APS are varied and could be confused with many disorders. The primary care provider needs to be aware of this syndrome in order to include it in the differential diagnosis and appropriately recognize and refer the patient in a timely manner.     

地塞米松对妊娠期血小板减少综合征患者的PLT、LDH、AST、ALT及妊娠结局的影响

目的研究地塞米松对妊娠期血小板减少综合征患者的血小板计数(PLT)、乳酸脱氢酶(LDH)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)及其妊娠结局的影响。方法将2014年3月至2015年4月在该院接受治疗的血小板减少综合征孕妇60例纳入观察组,根据其PLT减少程度分为Ⅰ级组、Ⅱ级组、Ⅲ级组,每组各20例,并选择同期60例健康孕妇作为对照组。给予观察组患者地塞米松治疗。对比两组孕妇及观察组中不同级别患者的PLT、LDH、AST、ALT的水平,以及并发症、妊娠结局、预后等情况。结果治疗后,观察组的PLT和LDH的水平均达到了正常的标准,与对照组比较,差异无统计学意义(P0.05)。观察组患者的并发症发生率与围生儿死亡率明显高于对照组(P0.05)。治疗后,观察组中Ⅰ级组的患者其血小板恢复时间为(4.78±1.45)d,明显高于Ⅲ级组患者的(2.82±0.86)d,差异有统计学意义(P0.05)。其Ⅰ级组患者的不良妊娠结局(50.00%)均明显高于Ⅱ级组(25.00%)与Ⅲ级组(20.00%)的患者(P0.05)。结论地塞米松治疗妊娠期血小板减少综合征,能够有效改善其不良的妊娠结局及患者的预后,但其疗效与临床分级有密切的关系。     

原发免疫性血小板减少症住院患儿临床分析

目的:研究儿童原发免疫性血小板减少症(ITP)慢性化的影响因素,比较不同一线治疗方案的疗效。方法:回顾性分析2013年9月至2018年10月于本院住院治疗的ITP患儿的临床资料。结果:共计301例ITP患儿纳入研究。男150例,女151例,中位年龄8(0.17-17)岁。新诊断ITP 110例(36.5%),持续性ITP 92例(30.6%),慢性ITP 99例(32.9%)。中位随访时间41.92(1.07-74.03)个月。截至随访终点(2019年10月),202例新诊断/持续性ITP患儿中,79例(59例新诊断ITP,20例持续性ITP)在初诊后1年内获得缓解,缓解率39.3%;122例(50例新诊断ITP,72例持续性ITP)进展为慢性ITP,慢性化率60.7%;1例行脾切除。99例慢性ITP患儿中,5例行脾切除。多因素Logistic回归分析显示,隐匿起病(OR=3.754,95%CI:1.882-7.488,P=0.000)增加疾病慢性化风险,而血小板膜糖蛋白抗体阳性(OR=0.446,95%CI:0.224-0.888,P=0.021)降低慢性化风险,抗体类型的亚组分析无差异(P=0.305)。新诊断和持续性ITP仅接受一线治疗的患儿,单独应用静脉注射免疫球蛋白(IVIG)或IVIG联合激素疗效均优于激素单药治疗(P=0.028,0.028),而单独应用IVIG与IVIG联合激素比较疗效无差异(P=0.086)。结论:儿童ITP隐匿起病慢性化风险升高,血小板膜糖蛋白抗体阳性降低慢性化风险。儿童新诊断和持续性ITP的一线治疗,单独应用IVIG或IVIG联合激素疗效均优于激素单药治疗。     

重组人血小板生成素在老年重症免疫性血小板减少症患者一线治疗中的短期疗效分析

目的:探讨重组人血小板生成素(recombinant human thrombopoietin,rhTPO)在老年重症原发免疫性血小板减少症(primary immune thrombocytopenia,ITP)患者一线治疗中的短期疗效.方法:回顾性选择2016年3月至2019年11月复旦大学附属中山医院青浦分院血液...     

Prevalence of immune thrombocytopenia: analyses of administrative data

BACKGROUND: The prevalence of immune thrombocytopenic purpura (ITP) in the USA is unknown. The paucity of data makes clinical trial design and resource allocation challenging. OBJECTIVES: We aimed to quantify the prevalence of ITP in one state and to report on utilization of resources. METHODS: The Maryland Health Care Commission supplied utilization data on all privately insured Maryland residents in 2002. We identified patients having two claims, separated by at least 30 days, for International Classification of Diseases, Ninth Revision, Clinical Modification code 287.3 (expected to be predominantly ITP). We excluded patients with concurrent diagnoses that made ITP unlikely. In sensitivity analyses, we varied the required visit interval between 14 and 180 days. We quantified ITP prevalence, resource utilization, and prevalence of concurrent autoimmune illnesses. RESULTS: The age-adjusted prevalence of ITP was 9.5 per 100,000 persons (10.5 per 100,000 when requiring a minimum 14-day interval and 4.5 per 100,000 with a 180-day interval). There was a predominance of males in childhood and of females in the middle-adult years, with an overall prevalence rate ratio of 1.9 for females to males. Twenty per cent of these patients were hospitalized, but emergency department use was rare, as was splenectomy. A concurrent diagnosis of multiple sclerosis was 25 times more prevalent than anticipated. CONCLUSIONS: We conclude that the prevalence of ITP in one populous state in the USA is comparable with that which has been reported in Europe. The suggested co-occurrence of ITP and multiple sclerosis in children merits further investigation.     

A Case of Evans' Syndrome Following Influenza Vaccine

Background

Evans' syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia purpura and autoimmune hemolytic anemia with a positive direct antiglobulin test in the absence of known underlying etiology.

Objectives

We present a case of Evans' syndrome following influenza vaccination.

Case Report

A 50-year-old man with no prior medical history developed Evans' syndrome 4 days after receiving influenza immunization. The patient improved following treatment with oral prednisone and intravenous immunoglobulin.

Conclusion

Influenza vaccine is one of the most commonly used vaccines worldwide, with millions of people being vaccinated annually. Despite its wide use, only sparse information has been published concerning any hematological effects of this vaccine. The rarity of such effects supports the safety of using this vaccine.     

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.     

Characterization of antibodies directed against platelet cryptantigens detected during the immunological study of 356 consecutive patients with presumed autoimmune thrombocytopenia (AITP)

SUMMARY. Cryptic antigens are detected by anti-bodies present in a wide spectrum of patients with or without thrombocytopenia, and even in healthy individuals. They are produced for unknown reasons and do not react with antigens of native platelets, but only with altered platelets. Cryptantigen antibodies may not only result in spuriously low platelet counts, but also in 'falsely' positive tests for platelet antibodies. We report our experience in the characterization of the different types of antibodies directed against cryptantigens of platelets: EDTA-dependent antibodies, PFA-dependent antibodies, EDTA-PFA-dependent antibodies and cold agglutinins. These antibodies were detected in the course of the serological study of 37 patients from a group of 356 (10%) whose blood was sent to our laboratory for platelet antibody testing. Pseudothrombocytopenia was diagnosed in 24 cases. Twenty-one of these showed EDTA-dependent or EDTA-PFA-dependent platelet agglutination and three were due to the presence of cold agglutinins. In 13 patients the thrombocytopenia was genuine. Eleven of these presented EDTA-dependent or EDTA-PFA-dependent antibodies in their serum and in the two remaining cases PFA-dependent antibodies were found. Cryptantigen antibodies were also detected in 9 out of 228 (4%) blood donors who were used as healthy controls in the platelet immunofluorescence test. In the light of the results obtained we put forward some guidelines to detect the presence of these antibodies and establish an accurate serological and clinical diagnosis of the autoimmune thrombocytopenias.