抗磷脂抗体与抗磷脂综合征的研究近况

综述抗磷脂抗体与抗磷脂综合征的研究近况，对抗磷脂抗体的实验室诊断、临床意义，以及抗磷脂综合征的临床表现和治疗进展作一详细介绍。     

抗磷脂综合征的实验室诊断

抗磷脂抗体综合征 (APS)的诊断标准 :患者至少有以下一项临床表现及一项实验室检查阳性 ,而且实验室阳性结果必须相隔 3个月以上有两次或两次以上阳性。临床表现为复发性静脉血栓形成 ,复发性动脉血栓形成 ,复发性妊娠失败 ,持续性血小板减少 ,网状青斑。实验室检查有狼疮抗凝物质(L AC)实验阳性 ,或 Ig G或 Ig M抗心磷脂 (与抗β2 GPI有关的 )抗体检测阳性。1　狼疮抗凝物 (L AC)检测检测 L AC的实验并不能测定抗体的滴定度 ,而仅仅是功能的检测。 L AC可通过抑制依赖磷脂的凝血实验来测定 ,可进行 L AC的筛选试验及确诊试验。1.…     

抗磷脂抗体诱导血栓形成的机制

最近研究显示,抗磷脂抗体与血栓的形成有密切关系,且抗磷脂抗体相关血栓的形成是多部位的,可以是动脉血栓亦可是静脉血栓。抗磷脂抗体诱导血栓形成的具体机制目前还不清楚,最新研究进展显示,抗磷脂抗体相关血栓的形成涉及多途径、多种相关分子的作用。     

抗磷脂综合征115例的临床特点及临床分类标准的演变和局限性的探讨

目的 研究抗磷脂综合征（APS）的临床特点，分析不同时期的APS的分类标准，以提高对这一疾病的认识。方法 回顾性分析1996-2006年在仁济医院根据不同时期的分类标准诊断的APS患者的临床和实验室特点。结果 1996-2006年满足至少1个分类标准的患者共120例，其中符合1988年Asherson分类标准者有101例，符合1999年Sapporo标准者为96例。符合2006年Sydney标准者为115例。在115例APS患者中，男女比例为1：10．5，平均病程为82．6个月，平均年龄为（41±12）岁。其中90例患者发生血栓事件，以深静脉血栓、脑梗死、皮肤血管为主。92例已婚有生育史的女性患者中。有46例发生病态妊娠。7例患者发生恶性APS。抗心磷脂抗体阳性86例，抗β2-糖蛋白Ⅰ（β2-GP Ⅰ）抗体阳性58例，狼疮抗凝物阳性27例。结论 常见的血栓部位为下肢深静脉、脑梗死和皮肤血管。Sydney标准增加抗β2-GP Ⅰ抗体作为一项实验室指标，提高了分类标准的敏感性，但是对于一些仅有血小板减少和实验室指标阳性的原发性APS患者的诊断存在局限性。另外，一些针对凝血因子的抗体对APS诊断的意义有待深入研究。     

抗磷脂综合征165例临床特征与分型

目的 分析抗磷脂综合征(APS)的临床特征与分型.方法 根据2006年更新的APS分类诊断标准及新的临床亚型的定义,回顾性分析北京协和医院住院的165例APS患者的临床分型,总结患者的临床表现及治疗,并分析抗磷脂抗体与血栓的相关性.结果 165例患者中,男:女为1:3.不同临床亚型的分类包括确诊APS 116例(70.3%),可能APS 34例(20.6%),血清阴性APS 10例(6.1%),微血管性APS 5例(3.0%).124例(75.2%)合并其他疾病,其中113例(91.1%)合并自身免疫病,以系统性红斑狼疮常见(79.6%).合并血栓者121例(73.3%),其中静脉血栓68例(56.2%),以下肢深静脉血栓最常见.仅有狼疮抗凝物(LA)阳性和仅有抗心磷脂抗体(ACL)阳性患者的血栓发生率分别为86.0%和65.5%(P<0.05).61例APTT延长的患者中,LA阳性50例(82.0%),ACL阳性34例(55.7%).结论 根据APS临床表现可分为多种临床亚型.APS合并血栓以静脉血栓多见.LA阳性较ACL阳性的患者血栓发生率高.APTT延长与LA的相关性较强.     

抗磷脂抗体与血栓性疾病：抗磷脂抗体的生物学特征

实验和临床研究结果均表明 ,血清中高滴度的抗磷脂抗体 (APA)是抗磷脂综合征 (APS)一系列相关症状产生和发展的关键。 APS亦称抗磷脂抗体综合征、抗磷脂——血栓形成综合征 (APL- T)或 Hughes综合征。它是近期发现的另一种非器官特异性的自身免疫性疾病 ,主要表现为血栓形成、习惯性流产及 (或 )血小板减少的临床症状群 ,并伴持续性 APA阳性 ,肢端顽固性溃疡等。APS可继发于各种疾病 ,但以风湿病为主 ,如系统性红斑狼疮 (SL E)等结缔组织病 ;病毒感染 ;其他感染原如支原体、螺旋体、原虫等感染 ;肿瘤如淋巴瘤、白血病及各种实体瘤…     

抗磷脂抗体诱导血栓形成的机制

最近研究显示，抗磷脂抗体与血栓的形成和密切关系，且抗磷脂抗体相关血栓的形成是多部位的，可以是动脉血栓亦可是静脉血栓。抗磷脂抗体诱导血栓形成的具体机制目前还不清楚，最新研究进展显示，抗磷脂抗体相关血栓的形成涉及多途径、多种相关分子的作用。     

抗磷脂抗体综合征和狼疮抗凝样物质

抗磷脂抗体综合征和狼疮抗凝样物质唐政早在１９０６年，Ｗａｓｓｅｒｍａｎ介绍了梅毒螺旋体的诊断学试验，以后称之为Ｗａｓｓｅｒ－ｍａｎ试验。该试验阳性的血清脂质成分除有梅毒螺旋体抗原以外还有磷脂成分；人们发现４０％或更多的ＳＬＥ患者该试验也呈阳性反应，另...     

抗磷脂抗体与血栓形成及其在慢性肝病中的研究进展

抗磷脂抗体(antiphspholipid antibody,APA)系自身抗体家族.APA分为狼疮抗凝物(lupus-anti-coagulant,LAC)和抗心磷脂抗体(anticardiolipin an-tibody,ACA)两大类,与之相关的抗磷脂综合征(antiphosphilipid syndrome,APS)是一种常见的获得性易栓症,其大多数症状都与血栓形成有关[1].近几年来,APA与慢性肝病的关系逐渐引起重视,主要集中于丙肝病毒(HCV)感染及酒精性肝病等 [2,3] 方面,以及与APA相关的血栓性疾病等,现将此方面的研究进展作一简要介绍.     

抗磷脂抗体综合征血栓形成的机制

抗磷脂抗体综合征 (APS)大多数症状与血栓形成有关 ,其血栓的发病机制目前尚不十分清楚 ,实验和临床结果表明 ,血清中高滴度的抗磷脂抗体 (APA)存在是血栓形成的关键 ,促血凝机理可能与以下几个方面有关。1　 APA对血管内皮细胞和血小板功能的影响细胞膜的主要结构成分是带阴电荷的磷脂 ,在 APS患者中 ,APA损伤血小板和内皮细胞膜 ,导致细胞膜内层带负电荷磷脂暴露于胞膜表面 ,APA与其结合后 ,使内皮细胞功能受损 ,APA一方面使磷脂酶 A2 诱导的花生四烯酸释放减少 ,导致前列环素 (PGI2 )合成降低 ,另一方面可选择性抑制凝血酶介导…     

Antiphospholipid syndrome

Antiphospholipid syndrome is an autoimmune systemic disorder characterized by arterial, venous, or small vessel thrombosis and/or recurrent early pregnancy loss, fetal loss, or pregnancy morbidity in the setting of documented persistent antiphospholipid antibodies that include the lupus anticoagulant, or moderate-high titer anticardiolipin, or anti-β2Glycoprotein I antibodies. Associated clinical manifestations include livedo reticularis, cutaneous ulcerations, thrombocytopenia, hemolytic anemia, valvular heart disease, and nephropathy. The degree of risk associated with antiphospholipid antibody depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. Current standard treatment for unprovoked thrombosis is long-term warfarin or other vitamin K antagonist therapy. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin, usually low-molecular-weight heparin. Optimal treatment for standard therapy failures or for certain nonthrombotic manifestations is uncertain, although nonanticoagulation therapies that address multiple demonstrated mechanisms of disease are being explored.     

Primary antiphospholipid syndrome in Latin American mestizo patients: clinical and immunologic characteristics and comparison with European patients

A great variety of clinical and immunological features have been described in patients with the antiphospholipid syndrome (APS), but information on their prevalence and characteristics in Latin American mestizo patients with the primary APS is scarce. To analyze the prevalence and characteristics of the main clinical and immunological manifestations in a cohort of patients with primary APS of mestizo origin from Latin America and to compare them with the European white patients, clinical and serological characteristics of 100 patients with primary APS from Colombia, Mexico, and Ecuador were collected in a protocol form that was identical to that used to study the "Euro-Phospholipid" cohort. The cohort consisted of 92 female patients (92.0%) and eight (8.0%) male patients. They were all mestizos. The most common manifestations were deep vein thrombosis (DVT; 23.0%), livedo reticularis (18.0%), migraine (18.0%), and stroke (18.0%). The most common pregnancy morbidity was early pregnancy losses (54.1% of pregnancies). Several clinical manifestations were more prevalent in the Latin American mestizo than in the European patients (transient global amnesia, pulmonary microthrombosis, arthralgias, and early pregnancy losses) and vice-versa (DVT, stroke, pulmonary embolism, and thrombocytopenia). Latin American mestizo patients with primary APS have a wide variety of clinical and immunological manifestations with several differences in their prevalence in comparison with European white patients.     

Antiphospholipid Syndrome

The antiphospholipid syndrome (APS) is an autoimmune systemic disease that is diagnosed when there is vascular thrombosis and/or pregnancy morbidity occurring with persistently positive antiphospholipid antibodies (aPL) (lupus anticoagulant test, anticardiolipin antibodies, and/or anti–β₂-glycoprotein I antibodies). Although International APS Classification Criteria have been formulated to provide a uniform approach to APS research, aPL may cause a spectrum of clinical manifestations, some of which are not included in these criteria. The main aPL-related cardiac manifestations include valve abnormalities (vegetations and/or thickening), myocardial infarction (MI), intracardiac thrombi, and myocardial microthrombosis. In this article, we will review the definition, etiopathogenesis, clinical manifestations, diagnosis, and treatment of aPL-related clinical events with emphasis on cardiac manifestations.     

Antiphospholipid syndrome and palindromic rheumatism: a new possible association

Objective The aim of this study was to report six patients with palindromic rheumatism (PR) in whom signs, symptoms, and/or serologic evidence of antiphospholipid syndrome (APS) developed.Methods The medical histories of the patients were reviewed with special emphasis on age, gender, duration of PR, and lapse of time until antiphospholipid antibodies were detected or APS was diagnosed. Three representative cases are described.Results Two patients were women and four were men. Their mean age was 49.3 years (range 36–80), and the mean duration of PR was 5.5 years (range 3–8). In all patients, raised titers of antiphospholipid antibodies were found on two or more occasions. Two patients developed clinical pictures compatible with APS, two showed symptoms which may be attributable for APS, and raised titers of antiphospholipid antibodies were found in only two.Conclusion It seems that the appearance of these two uncommon conditions together is more than coincidental and may point to a previously unreported clinical association.     

Antiphospholipid antibodies--we are not quite there yet

The diagnosis of antiphospholipid syndrome is predominantly made in the laboratory and depends on the persistent presence of antiphospholipid antibodies in individuals with thrombosis or pregnancy morbidity. Correct diagnosis of the syndrome is imperative to prevent unnecessary long secondary thromboprophylaxis. Three antiphospholipid antibody subtypes are included in the classification criteria of the antiphospholipid syndrome: lupus anticoagulants, anticardiolipin antibodies and anti-β2-glycoprotein I antibodies. Only lupus anticoagulants are undisputedly associated with thrombosis, which is why the serological criteria of the antiphospholipid syndrome are under debate. All of the assays used to detect antiphospholipid antibodies are in need of better standardization, although progress has been made in the detection of lupus anticoagulants. The inconsistent association between both anticardiolipin and anti-β2-glycoprotein I antibodies and thrombosis is a cause for alarm. We are in need of better assays to detect those individuals at risk for thrombosis and population-based prospective studies to provide us with accurate risk assessments.     

Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients

OBJECTIVE: To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression. METHODS: The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database. RESULTS: The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of 42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients. CONCLUSION: APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.     

Antiphospholipid antibodies in children with systemic lupus erythematosus: a prospective study in northern India

Twenty-seven children with systemic lupus erythematosus (SLE) were tested for antiphospholipid antibodies (APLA), i.e. lupus anticoagulant and immunoglobulin (Ig)G or IgM anticardiolipin antibodies (ACLA), with beta-2 glycoprotein I as cofactor, in a single-centre, prospective study over 2 years. Eighteen patients (67%) tested positively for one or the other APLA during the course of the study. Twelve children (44%) tested positively for IgG ACLA and ten (37%) for IgM ACLA, whereas eight (30%) were positive for lupus anticoagulant. In two patients with thrombosis, IgG anticardiolipin positivity was seen to be variable. Unlike the results of most other reports in the literature, lupus anticoagulant positivity was not consistently associated with thrombosis. A majority of the children (83%) tested positively for ACLA during disease activity. Immunoglobulin G and IgM ACLA positivity did not correlate significantly with disease status. The results of this prospective study would indicate that, though frequently present, APLA may be unable to be predictive of disease behaviour in children with SLE.     

Primary antiphospholipid syndrome (PAPS)

Summary Antiphospholipid antibodies (aPL) interfere with the coagulation system and can cause thrombosis and other clotting disorders. The combination of recurrent venous thrombosis, arterial embolism and recurrent fetal loss is nowadays considered to be primary antiphospholipid syndrome (PAPS), provided an underlying systemic lupus erythematosus (SLE) has been excluded and aPL have been detected. We report on two patients with PAPs, and show the course of their IgG- and IgM-anticardiolipin antibody (aCL) titers during immunosuppressive therapy with prednisone and azathioprine or cyclophosphamide. Over a period of 18 months this therapy was effective in preventing relapses of thrombo-embolism and other complications. Therapy with cyclophosphamide resulted in normalization of the aCL titers in one of the two reported cases. Azathioprine treatment reduced the aCL titer in the other patient, without fully normalizing it. Based on our observation, we propose to treat PAPS-associated severe and recurrent thrombo-embolic complications by aggressive immunosuppression, including azatioprine and cyclophosphamide.