抗磷脂抗体与抗磷脂血栓综合征

抗磷脂抗体（ＡＰＡ）与抗磷脂血栓综合征（ＡＰＬ－Ｔ）的发生密切相关,但ＡＰＡ引起ＡＰＴ－Ｔ的发病机制仍不清楚,近年来ＡＰＡ通过抑制蛋白Ｃ（ＰＣ）途径,引起获得抗活化蛋白Ｃ现象进而导致血栓的研究受到关注。本主要将抗磷脂血栓综合征的研究进展作一综述。     

抗心磷脂抗体与反复自然流产关系的探讨

应用间接ＥＬＩＳＡ法检测１０５例反复自然流产患者血清中的抗心磷脂抗体，同时对ＡＮＡ、扩ｄｓ－ＤＮＡ、抗－Ｓｍ，抗－ＲＮＰ、ＲＦ进行了测定。结果表明：ＲＳＡ组ＡＣＡ阳性率为２８．６％，明显高于其他自身抗体及对照组（Ｐ＜０．０１），ＡＣＡ与ＲＳＡ患者的孕龄及流产次数无相关性（Ｐ＞０．０５），三种类别Ｉｇ中，以ＩｇＧ、ＩｇＧ、ＩｇＭ型ＡＣＡ检出率较高，中等或高水平的阳性结果占３３．３％（１０／３０），其     

血栓栓塞症患者抗活化的蛋白C的研究

目的 探讨抗活化的蛋白Ｃ（ＡＰＣＲ）现象在中国人血栓栓塞症发病中的作用。方法 用ＡＰＴＴ法检测ＡＰＣＲ敏感比率（ＡＰＣＲ－ＳＲ）来研究４０例深静脉血栓症（ＤＶＴ）患者、５２例脑血栓形成患者和１００例正常人的ＡＰＣＲ发生率;用多聚酶链反应－限制性内切酶长度多态性（ＰＣＲ－ＲＦＬＰ）来检测ＦＶ Ｌｅｉｄｅｎ突变;用免疫火箭电泳测血浆总蛋白Ｓ和游离蛋白Ｓ。结果 正常人的正常化ＡＰＣＲ－ＳＲ（ｎ－ＡＰＣＲ     

血透患者检测抗HCV IgM的临床意义

为探讨丙型肝炎ＩｇＭ抗体测定在血液透析患者中的临床意义,采秀间接ＥＬＩＳＡ法检测抗ＨＣＶ ＩｇＭ。同时采用ＥＬＩＳＡ测抗ＨＣＶ ＩｇＧ,ＲＴ－ＰＣＲ法测ＨＣＶ ＲＮＡ,并进行比较。结果示６２例血液透析病人中,抗ＨＣＶ ＩｇＭ阳性２７例（４３．６％）,抗ＨＣＶ ＩｇＧ阳性２９例（４６．８％）,ＨＣＶ ＲＮＡ阳性３４例（５４．８％）,任一项阳性３７例（５９．７％）;抗ＨＣＶ ＩｇＭ与ＨＣＶ ＲＮＡ检测     

静脉及心脑血栓性疾病抗活化的蛋白C的研究

为探讨抗活化的蛋白Ｃ（ＡＰＣＲ）及其基因型在中国人血栓性疾病的发病情况，用活化的部分凝血活酶时间（ＡＰＴＴ）以加和不加活化的蛋白Ｃ（ＡＰＣ）的比值（ＡＰＣ－ＳＲ）检测ＡＰＣＲ；用多聚酶链反应扩增因子Ⅴ第１０外显子（包含５０６位密码子）的２２０ｂｐ片段，再用限制性内切酶ＭｎｌⅠ消化检测其基因型。共检测了４６例静脉血栓和下肢动脉血栓，５８例心、脑梗塞，７４例冠心病及４０名正常人的ＡＰＣＲ及其基因型。结果表明血栓性疾病患者与正常人的ＡＰＣＲ无明显差异，亦没有发现与ＡＰＣＲ相关的基因型，提示ＡＰＣＲ很可能不是中国人血栓性疾病常见相关病因     

反复自然流产患者血浆前列环素和血栓素水平及其与抗心…

用ＲＩＡ法检测了４６例不明原因的反复流产（ＲＳＡ）患者血浆６－Ｋｅｔｏ－ＰＧＦ１α和ＴＸＢ２水平，并对其与抗心磷脂抗体（ＡＣＡ）的关系进行了研究。结果表明：ＲＳＡ患者有一定程度的血栓素升高和前列环素的降低，其中尤以ＡＣＡ阳性者更为明显，Ｔ／Ｋ比值较对照组显著增高Ｐ〈０．０１。     

ELISA检测抗重组Sm—D与IBT,CIE检测抗Sm抗体的比较

利用重组并纯化的Ｓｍ－Ｄ抗原，通过ＥＬＩＳＡ对２８例系统性红斑狼疮（ＳＬＥ）等结缔组织病（ＣＴＤ）患者和 ３０例正常人及非 ＣＴＤ患者血清中的抗 Ｓｍ－Ｄ抗体进行检测，并与用免疫印迹（ＩＢＴ）、对流免疫电泳（ＣＩＥ）法检测抗Ｓｍ抗体进行比较。结果显示抗Ｓｍ－Ｄ重组抗原的抗体仅在 ＳＬＥ患者中出现，其阳性率为 ６５％； ＩＢＴ法抗 ２９／２８ＫＤ Ｓｍ的阳性率为 ６０％，抗 １３．５ＫＤＳｍ的阳性率为４５％； ＣＩＥ法抗Ｓｍ的阳性率为５５％。用ＩＢＴ和ＣＩＥ法在混合性结缔组织病（ＭＣＴＤ）和原发性干燥综合征（ＩＳＳ）中亦检测到２９／２８ＫＤ的Ｓｍ的抗体和出现Ｓｍ的沉淀线。显示以重组、纯化的Ｓｍ－Ｄ抗原为底物，通过ＥＬＩＳＡ检测抗Ｓｍ－Ｄ抗体具有特异性强、敏感性高的优点。     

彩超在抗磷脂血栓综合征诊断中的应用

抗磷脂血栓综合征 (ＡＰＬ Ｔ)是一组表现为血栓形成、习惯性流产和 (或 )血小板减少的临床征候群 ,并伴持续性抗磷脂抗体 (ＡＰＡ)阳性[1] 。本研究就 5 8例系统性红斑狼疮 (ＳＬＥ)患者 ,应用彩色多普勒血流显像 (ＣＤＦＩ)并结合实验室检测分析 ,对ＡＰＬ Ｔ的诊断价值进行探讨。资料与方法一、研究对象1998年 6月至 2 0 0 0年 2月我院门诊及住院的 5 8例ＳＬＥ患者 ,男 7例 ,女 5 1例 ,年龄 15～ 80岁 ,平均 36岁。ＣＤＦＩ检查双下肢深静脉及症状部位的血管。正常对照组 2 0例为健康献血员 ,男 2例 ,女 18例 ,年龄 17～ 6 4岁 ,平均 32…     

输血后急性丙型肝炎患者抗-HCV和病毒血症观察

输血后急性丙型肝炎患者抗－ＨＣＶ和病毒血症观察４３００７１湖北医科大学附属第二医院左学兰骆名其许友芝第２代ＥＬＩＳＡ法（ＥＬＩＳＡⅡ）检测丙型肝炎病毒抗体（抗－ＨＣＶ）和聚合酶链反应（ＰＣＲ）检测ＨＣＶＲＮＡ，已常规应用于临床，为了估价这些血清学和分...     

广东人抗活化蛋白C及FV Leiden突变的检测

为了解活化蛋白Ｃ抵抗（ＡＰＣＲ）以及凝血因子Ｖ Ｌｅｉｎｄｅｎ（ＦＶ Ｌｅｉｄｅｎ）突变在广东人群及血栓性疾病患者中发生的情况,用序列特异性引物ＰＣＲ（ＰＣＲ－ＳＳＰ）方法检测１３０名广东籍正常人ＦＶ Ｌｅｉｄｅｎ突变,其中５７名正常人用ＡＰＣ－ＡＰＴＴ方法检测了ＡＰＣＲ。结果有３名正常人ＡＰＣＲ阳性。但所有的样本均未发现ＦＶ Ｌｅｉｄｅｎ突变,ＡＰＣＲ阳性是否与其他未知的基因缺陷有关,有待进一步     

系统性红斑狼疮抗活化的蛋白C研究

目的了解抗活化的蛋白C(APCR)在系统性红斑(SLE)患者中的发生情况,并进一步探讨SLE患者发生血栓的机制。方法采用APG-KPTT法,ELISA法和PTT-LA法分别对36例SLE患者及20例正常对照(NC)进行APCR、抗心磷脂抗体(ACA)和狼疮抗凝物(LA)检测。结果SLE患者APCR阳性率(58%)明显高于NC组(5%)(P<0.005),APCR阳性患者中血栓发生率(27.6%)明显高于APCR阴性患者(4.8%)(P<0.01),患者LA阳性率(22%)明显高于对照组(0/10)(P<0.05),患者ACA-IgG及IgM明显高于对照组(P<0.05),而IgA与对照组差异不显著(P>0.05),LA阳性组中的APCR阳性率(90.9%)明显高于LA阴性组(53.8%)(P<0.05),ACA阳性组中的APCR阳性率(64.7%)与ACA阴性组(60.6%)未发现明显相关性(P>0.05)。结论APCR在国人SLE患者中有较高的发生率且与LA有明显相关性。APCR可能是SLE患者诱发血栓的主要原因之一。     

Antiphospholipid syndrome

Antiphospholipid syndrome has received considerable attention from the medical community because of its association with a number of serious clinical disorders, including arterial and venous thromboembolism, acute ischemic encephalopathy, recurrent pregnancy loss, thrombocytopenia, and livido reticularis. It can occur within the context of several diseases, mainly autoimmune disorders, and is then called secondary antiphospholipid syndrome. However, it may be also be present without any recognizable disease, or so-called primary antiphospholipid syndrome. There is no defined racial predominance for primary antiphospholipid syndrome, although a higher prevalence of systemic lupus erythematosus (SLE) occurs in African Americans and the Hispanic population. Multiple terms exist for this syndrome, some of which can be confusing. Lupus anticoagulant syndrome, for example, is a misleading term, because patients may not necessarily have SLE, and it is associated with thrombotic rather than hemorrhagic complications. To avoid further confusion, antiphospholipid syndrome is currently the preferred term for this clinical syndrome. Antiphospholipid antibodies are found in 1% to 5% of young healthy control subjects; however, the incidence increases with age and coexistent chronic disease. The syndrome occurs most commonly in young to middle-aged adults; however, it also can occur in children and the elderly. Among patients with SLE, the prevalence of antiphospholipid antibodies is high, ranging from 12% to 30% for anticardiolipin antibodies, and 15% to 34% for lupus anticoagulant antibodies. In general, anticardiolipin antibodies occur approximately five times more often then lupus anticoagulant in patients with antiphospholipid syndrome. This syndrome is the most common cause of acquired thrombophilia, associated with either venous or arterial thrombosis or both. It is characterized by the presence of antiphospholipid antibodies, recurrent arterial and venous thrombosis, and spontaneous abortion. Rarely, patients with antiphospholipid syndrome may have fulminate multiple organ failure, or catastrophic antiphospholipid syndrome. This is caused by widespread microthrombi in multiple vascular beds, and can be devastating. Patients with catastrophic antiphospholipid syndrome may have massive venous thromboembolism, along with respiratory failure, stroke, abnormal liver enzyme concentrations, renal impairment, adrenal insufficiency, and areas of cutaneous infarction. According to the international consensus statement, at least one clinical criterion (vascular thrombosis, pregnancy complications) and one laboratory criterion (lupus anticoagulant, antipcardiolipin antibodies) should be present for a diagnosis of antiphospholipid syndrome. The hallmark result from laboratory tests that defines antiphospholipid syndrome is the presence of antibodies or abnormalities in phospholipid-dependent tests of coagulation, such as dilute Russell viper venom time. There is no consensus for treatment among physicians. Overall, there is general agreement that patients with recurrent thrombotic episodes require life-long anticoagulation therapy and that those with recurrent spontaneous abortion require anticoagulation therapy and low- dose aspirin therapy during most of gestation. Prophylactic anticoagulation therapy is not justified in patients with high titer anticardiolipin antibodies with no history of thrombosis. However, if a history of recurrent deep vein thrombosis or pulmonary embolism is established, long-term anticoagulant therapy with international normalized ratio (INR) of approximately 3 is needed.     

抗磷脂蛋白抗体、活化蛋白C抵抗与深静脉血栓形成的关系研究

目的探讨抗磷脂蛋白抗体（APA）、活化蛋白C抵抗（APCR）与深静脉血栓形成（DVT）之间的关系及其临床意义。方法选取100例DVT患者和100例正常对照者,分别采用ELISA法检测ACA（IgG,IgM,IgA）,APTT法检测LA,APTT＋／-APC法检测APCR。PCR-限制性片断长度多态性方法（PCR—RFLP）检测FV Leiden变异。结果DVT组患者APA、APCR的总阳性率分别为34％、4％,与对照组相比差异显著;APA阳性组APCR阳性率（8．82％）明显高于APA阴性组（1．51％）,4例APCR阳性患者均未检测到FV Leiden突变。4例APCR阳性患者中有3例APA阳性。并能被血小板磷脂纠正。结论抗磷脂抗体、活化蛋白C抵抗与深静脉血栓形成密切相关,抗磷脂蛋白抗体及其产生获得性APCR是高凝状态和深静脉血栓形成的重要原因。     

Pregnancy complicated by antiphospholipid antibodies

The manifestations of antiphospholipid antibodies in pregnancy are multiple and include maternal arterial and venous thrombosis, spontaneous abortion, intrauterine fetal death, intrauterine growth retardation, and preeclampsia. Maternal complications may also arise in the puerperium with the development of an autoimmune pleuropulmonary postpartum syndrome. Currently, there is confusion in the literature regarding appropriate treatment of patients known to possess these antibodies. We have reported the case of a patient at 29 weeks' gestation who had elevated blood pressure, proteinuria, and early intrauterine growth retardation. Studies were positive for the presence of both lupus anticoagulant and anticardiolipin antibodies. After delivery, chest pain and a pleural effusion developed as further manifestations of the patient's autoimmune disease.     

The antiphospholipid syndrome]

Antiphospholipid antibodies such as anticardiolipin antibodies and lupus anticoagulant are frequently detected in sera from patients with systemic lupus erythmatosus and from those with related autoimmune disorders. Thromboembolic manifestations, fetal losses or thrombocytopenia in association with antiphospholipid antibodies, are hallmarks of the antiphospholipid syndrome (APS). Recent studies indicates that anticardiolipin antibodies bind to beta 2-glycoprotein I and that a part of lupus anticoagulant binds to beta 2-glycoprotein I or to prothrombin. Antiphospholipid antibodies might induce thrombosis by altering the function of vascular endothelial cells or by accelerating the progression of atherosclerosis. Warfarin, heparin or low dose aspirin have been recommended to prevent recurrent episodes of thrombosis in patients with the APS.     

Antiphospholipid syndrome and its role in pediatric cerebrovascular diseases: A literature review

Antiphospholipid syndrome (APS) or Hughes syndrome is an acquired thromboinflammatory disorder. Clinical criteria of APS diagnosis are large- and small-vessel thrombosis as well as obstetric problems; laboratory criteria are the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies and anti-β2-glycoprotein-1). The presence of at least 1 clinical and 1 laboratory criterion allows definitive diagnosis of APS. Primary APS is diagnosed in patients without features of connective tissue disease; secondary APS is diagnosed in patients with clinical signs of autoimmune disease. A high frequency of catastrophic APS as well as a high tendency to evolve from primary APS to secondary syndrome during the course of lupus and lupus-like disease is a feature of pediatric APS. The most characteristic clinical presentation of APS in the pediatric population is venous thrombosis, mainly in the lower limbs, and arterial thrombosis causing ischemic brain stroke. Currently, no diagnostic criteria for pediatric APS exist, which probably results in an underestimation of the problem. Similarly, no therapeutic procedures for APS specific for children have yet been established. In the present literature review, we discussed data concerning APS in children and its role in cerebrovascular diseases, including pediatric arterial ischemic stroke, migraine and cerebral venous thrombosis.     

静脉血栓的抗磷脂蛋白抗体与抗凝血、纤维蛋白溶解关系

为了探讨静脉血栓的病因病理及其与抗凝血、纤维蛋白溶解的关系 ,对 4 7例静脉血栓 (VT)患者用酶联免疫法检测抗心肌磷脂抗体 (ACA) ,用凝血法测定狼疮抗凝物 (LA)和抗活化蛋白C抗性 (APCR) ,用多聚酶链反应内切酶法鉴定因子VLeiden ,用发色底物法测定抗凝血酶Ⅲ (ATⅢ )、蛋白C(PC)、纤溶酶原 (Plg)、组织纤溶酶原激活物 (tPA)、组织纤溶酶原激活物抑制物 (tPAI)等抗凝血、纤维蛋白溶解活性。结果表明 :VT患者中 3 4 %有ACA和 (或 )LA阳性 ,其中以ACAIgG和LA为主 ;9.5 %的Plg缺乏 ,8.3 %的tPAI升高 (明显高于对照 ,P <0 0 0 5 ) ;ATⅢ、PC、tPA缺乏者依次为 4 .5 %、4 .5 %、2 .8% (与对照无差异性 ,P >0 .0 5 ) ;ATⅢ、PC、Plg联合缺乏者 1例 ;APCR未发现相应的factorVLeiden ;抗磷脂蛋白抗体 (APA)阳性和阴性组之间的各抗凝血和纤维蛋白溶解活性没有明显差异性 ;4例APCR阳性 ,3例ACA和 (或 )LA阳性 ,这 3例血浆和正常血浆混合后 2例APCR并没有完全得到纠正。结论 :抗磷脂蛋白抗体和纤维蛋白溶解异常是VT较多见的相关病理因素 ;LA和 (或 )ACA干扰蛋白C抗凝血途径 ,使之形成获得性APCR ,而此APCR可能是体内导致易栓的病因之一。     

The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies.

The importance of testing for anticardiolipin antibodies (aCL) in the diagnosis of antiphospholipid syndrome (APS) in patients with thrombosis has recently been challenged (ISTH SSC meeting, Boston 2002). We have analyzed the antiphospholipid serology of 123 patients with persistent antiphospholipid antibodies (aPL) attending our hematology department. The cohort was tested for anti-beta(2)-glycoprotein I (beta(2)-GPI) antibodies and aCL of IgG and IgM class and for lupus anticoagulant (LA). Ninety-six of these patients fulfilled Sapporo clinical criteria for APS and 70 of these patients had venous and/or arterial thrombosis. Patients with LA plus anti-beta(2)-GPI antibodies had significantly higher levels of IgG aCL and anti-beta(2)-GPI antibodies than those exhibiting positivity for only LA or anti-beta(2)-GPI antibodies (P < 0.05). Patients with aCL IgG levels over 60 GPLU were found in all cases to be positive for LA and anti-beta(2)-GPI antibodies; 25.2% (31/123) of all patients and 26.04% (25/96) of patients fulfilling Sapporo clinical criteria for APS were positive for aCL only. The mean IgG aCL level in the Sapporo clinical criteria positive patients who had aCL only was 11.5 GPLU (normal < 5 GPLU). These data indicate that omission of aCL testing from the clinical investigation of APS could lead to a failure to diagnose the syndrome in a proportion of patients.     

Apolipoprotein H (apoH)-dependent autoantibodies and apoH protein polymorphism in selected patients showing lupus anticoagulant activity.

Apolipoprotein H (apoH) is considered to be a necessary cofactor for the binding of certain antiphospholipid antibodies to anionic phospholipids. Some apoH-dependent antiphospholipid antibodies also exert lupus anticoagulant (LA) activity, which seems to depend on antiphospholipid antibody epitope specificity. The aim of this study was to evaluate whether the presence of less frequent apoH alleles may induce structural or conformational changes in these "LA-dependent" regions that may initiate more frequent autoimmune responses in subjects. We selected patients with confirmed LA activity and none or low titers of anticardiolipin antibodies that had been sent to the laboratory for routine antiphospholipid antibody determination. Many of them had some clinical manifestation of antiphospholipid syndrome. Antibodies to apoH were determined with a commercially available anticardiolipin/apoH ELISA kit. ApoH protein polymorphism (apoH phenotype) was demonstrated by isoelectric focusing and immunoblotting. Our results showed that 47/74 (63.5%) of our selected LA-positive patients also had elevated apoH-dependent antiphospholipid antibody titers. These results point to two subgroups of patients according to the LA potency of apoH-dependent antibodies. A strong positive correlation (non-linear or linear) for apoH-dependent antibody titers and LA activity was observed in both subgroups of patients. In this study, we did not find significant differences in the distribution of apoH phenotypes among control subjects and patients with apoH-dependent/LA-positive auto- antibodies.     

Effect of heat inactivation and sheep erythrocyte adsorption on the titer of anticardiolipin antibodies in primary antiphospholipid syndrome and healthy blood donors' sera.

The standard enzyme linked immunosorbent assay (ELISA) currently in use for detection of anticardiolipin antibodies (ACA) was used to evaluate the influence of heat inactivation and sheep erythrocyte adsorption on individual optical density (OD) of sera from healthy blood donors or patients with primary antiphospholipid syndrome. Each sample was tested after single or combined maneuvers as follows: adsorbed, adsorbed and inactivated, only inactivated, and compared to basal readings. A significant increase of ACA titers did occur after inactivation of normal sera, but adsorption had no effect. In contrast, neither inactivation nor adsorption changed ACA titer in primary antiphospholipid syndrome sera as a group, although in certain sera there were changes. This observation may suggest the presence in normal serum of a thermolabile factor which modulates ACA binding to its antigen and the reactivity of the anticardiolipin antibodies of the primary antiphospholipid syndrome with sheep erythrocyte membrane phospholipids.