抗心磷脂抗体与狼疮性肾炎患者肾功能的关系

目的探讨狼疮性肾炎患者抗心磷脂抗体(ACA)对肾功能的影响。方法对68例狼疮性肾炎患者随访1年,测定其血清ACA及肾功能。结果狼疮性肾炎肾功能正常组和肾功能不全组的IgG鄄ACA、IgA鄄ACA、IgM鄄ACA阳性率分别为40.5%、35.7%、40.5%(P<0.01)及57.7%、38.5%、46.2%(IgG,P<0.01;IgA,IgM,P<0.05),与对照组相比差异有显著性。随访期ACA阳性组肾功能不全者明显超过ACA阴性组(P<0.05),随着ACA转阴,肾功能逐渐恢复。结论ACA与狼疮性肾炎的肾功能损害密切相关,应用泼尼松和环磷酰胺降低血清ACA滴度,肾功能损害也随之好转。     

系统性红斑狼疮合并抗磷脂综合征患者的临床分析

目的 研究系统性红斑狼疮合并抗磷脂综合征(SLE-APS)患者的临床特点.方法 对39例SLE-APS患者的临床和实验室资料进行回顾性分析.结果 39例患者中,有31例共发生了48次血栓栓塞事件,以深静脉血栓及脑梗死为主.26例已婚有生育史女性患者中,有12例发生病态妊娠.28例抗心磷脂抗体阳性;16例狼疮抗凝物阳性.24例患者先确诊SLE,平均9.5年后又出现APS样表现;12例先出现反复病态妊娠或血栓事件,平均4.8年后演变为SLE;3例一发病便同时符合SLE和APS的分类标准.有5例在发生血栓事件或病态妊娠时的狼疮活动指数<5分.结论 SLE-APS患者血栓事件及病态妊娠发生率增多.APS可出现于SLE之前、之后或同时.狼疮患者可以在病情稳定期出现APS的表现.详细询问病史、常规检测抗心磷脂抗体,有助于发现SLE-APS的高危因素,积极预防APS的发生.     

抗磷脂抗体与血栓形成

抗磷脂抗体（包括狼疮样抗凝物及抗心磷脂抗体）是多种原因诱发的异质性自身抗体，进一步的研究表明抗磷脂抗体与血栓形成密切相关，检测抗磷脂抗体对临床医师预测，诊治血栓病具有一定的指导意义，本文综述了抗磷脂抗体的分类，与血栓形成的关系及检测方法，防治措施。     

抗磷脂综合征发病机制及诊治进展

抗磷脂综合征(antiphospholipid syndrome,APS)主要表现为血栓形成或病态妊娠,实验室检测抗磷脂抗体(an-tiphospholipid antibody,APL)阳性,如抗心磷脂抗体(anticardiolipin antibody,ACA)、抗β2-糖蛋白1(β2-glycoprotein l,β2-GP1)抗体及狼疮抗凝物(lupus anticoagulant,LAC)。β2-GP1及其抗体在APS发病机理中的作用日益受到人们的重视。APS累及全身多个系统,治疗上除肝素、华法林和阿司匹林外,还可试用免疫抑制剂、大剂量丙种球蛋白等,其他与发病机制相关的免疫治疗仍在进一步研究中。     

554例抗磷脂抗体阳性病例的临床分析

目的探讨抗磷脂抗体(APA)阳性患者的临床与实验室特征。方法选取2015年7月至2016年9月该院就诊并进行APA检测的2 382例患者作为研究对象,其中APA阴性患者1 828例(APA阴性组),至少1项APA阳性(ACA为中高滴度阳性)患者554例(APA阳性组)。APA阳性组中最终仅42例被确诊为抗磷脂综合征患者(APS患者)。采用稀释蝰蛇毒时间(DRVVT)法和硅土凝固时间(SCT)法进行检测狼疮抗凝物(LAC),同时采用酶联免疫吸附试验检测抗β2糖蛋白I抗体(aβ2GPI)和抗心磷脂抗体(ACA)。结果 APA阳性组LAC、aβ2GPI、ACA阳性率分别为52.3%、58.3%、17.0%;APA阳性组性别比及血栓形成和病态妊娠发生率明显高于APA阴性组,差异有统计学意义(P0.01);APS患者中血栓形成和病态妊娠的发生率分别为73.8%、26.2%,LAC、aβ2GPI、ACA阳性率分别为95.2%、76.2%、42.9%,DRVVT法、SCT法及两者联合检测LAC的阳性率分别为4.8%、11.9%和78.6%。结论抗磷脂抗体阳性是血栓形成和病态妊娠发生的危险因素,APS血栓事件以动脉血栓为主,LAC检测对APS的诊断灵敏度高。     

抗膜突蛋白抗体在抗磷脂综合征中的初步研究

目的 :分析抗磷脂综合征患者抗膜突蛋白抗体表达情况,并探讨抗膜突蛋白抗体在抗磷脂抗体相关性血栓发生中可能的作用。方法:采用酶联免疫吸附试验检测70例抗磷脂综合征患者(包括50例抗磷脂抗体相关性血栓患者和20例抗磷脂抗体相关性反复流产者)及100名正常对照者的血清抗膜突蛋白抗体及其他自身抗体的阳性率。制备鼠源性单克隆抗膜突蛋白抗体,加入正常人富血小板血浆中,检测其诱导血小板聚集的能力;同时加入单克隆抗体和膜突蛋白,检测血小板聚集抑制率。结果:在50例抗磷脂抗体相关性血栓患者和20例抗磷脂抗体相关性反复流产患者中,抗N端膜突蛋白抗体阳性率分别为76%和65%,显著高于其他自身抗体(抗C端膜突蛋白抗体、抗血小板抗体、抗心磷脂抗体、抗β2糖蛋白Ⅰ抗体)的阳性率。鼠源性单克隆抗N端膜突蛋白抗体有诱导血小板聚集的作用,而该作用可被N端膜突蛋白抑制,但不能被二磷酸腺苷激活途径抑制物精氨酸-甘氨酸-天冬氨酸-丝氨酸四肽所抑制。结论:大部分抗磷脂抗体综合征患者存在抗N端膜突蛋白抗体阳性,且该抗体的产生可能与抗磷脂综合征患者血栓形成的发病机制相关。抗膜突蛋白抗体在诊断和治疗抗磷脂综合征中的应用值得进一步探索。     

抗磷脂抗体综合征的发病机制和临床实验诊断方法的现在与未来

抗磷脂抗体综合征(antiphospholipid syndrome，APS)在临床上表现为反复的动脉、静脉血栓、习惯性流产和血小板减少等，这些症状可单一出现或多个共同存在。在患者的血清中可检出狼疮抗凝因子(lupus anticoagulant，LA)或抗心磷脂抗体(anticar diolipin antibody，aCL)。APS的基本病理改变表现     

抗磷脂综合征55例临床分析

目的:探讨抗磷脂综合征(APS)的临床特点和诊治经验,提高对该病的诊治水平.方法:收集并回顾性分析 55例APS患者的临床资料.结果:男8例,女47例,男女比例1∶5.9,确诊时年龄为15 ～ 71岁,中位年龄34岁.原发性APS(PAPS)35例,继发性APS(SAPS)20例.55例患者中,30例(54.5%)发生血栓事件,血栓事件以下肢深静脉血栓(27.3%)和脑梗死(14.5%)常见.18例(32.7%)出现血小板减少.2例患者发生恶性APS.24例(43.6%)女性患者出现病态妊娠.所有患者抗心磷脂抗体(ACL)均为阳性.结论:APS以血栓形成和病态妊娠为主要特点,其免疫学特征主要是高滴度ACL阳性,由于血栓可以累及多个部位,首发症状多样化,早期诊治是改善预后的关键.     

安子合剂治疗抗心磷脂抗体阳性致先兆流产191例临床研究

目的观察中药安子合剂治疗抗心磷脂抗体阳性致先兆流产的临床疗效。方法选择191例抗心磷脂抗体阳性的先兆流产患者为观察对象，对其中67例采用安子合剂口服．124例采用安子合剂口服加黄体酮肌肉注射的方法进行治疗。抗心磷脂抗体采用酶联免疫吸附法测定。结果安子合剂组保胎成功率为85．07％（57例），其中继续妊娠者抗心磷脂抗体转阴率为100％；安子合剂加黄体酮组的保胎成功率为86．29％（107例）。其中继续妊娠者抗心磷脂抗体转阴率为98．59％；两组保胎成功率以及抗心磷脂抗体转阴率比较，差别无统计学意义（P〉0．05）。结论单纯用中药安子合剂口服治疗抗心磷脂抗体阳性的先兆流产有显著的临床疗效。     

抗心磷脂抗体在血液病患者中的改变

抗磷脂抗体 (ＡＰＡ)是一类异质免疫球蛋白 ,在体内可以与带负电的磷脂结合 ,在参与凝血过程时 ,影响多种依赖磷脂的反应体系 ,可引起凝血功能的紊乱。目前认为抗磷脂抗体与血栓形成关系甚为密切[1,2 ] 。抗磷脂抗体可分为狼疮样抗凝物 (ｌｕｐｕｓ ｔｙｐｅａｎｔｉｃｏａｇｕｌａｎｔｓ,ＬＡＣ)和抗心磷脂抗体 (ａｎｔｉ ｃａｒｄｉｏｌｉｐｉｎａｎｔｉｂｏｄｉｅｓ ,ＡＣＡ)两大类。近年来对恶性血液病的研究发现 ,在恶性血液病的病程进展中常可以伴有血栓和(或 )弥散性血管内凝血 (ＤＩＣ)的出现。为了进一步研究ＡＰＡ与血液病患者出…     

Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome

Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared.     

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.     

Clinicomorphological features of nephropathy in primary and secondary antiphospholipid syndrome

AIM: To investigate specific features of extrarenal manifestations of antiphospholipid syndrome (APS) in patients with APS-associated nephropathy (APSN) in primary APS and lupus nephritis (LN) with secondary APS; to compare clinicomorphological signs of APSN in primary and secondary APS. MATERIAL AND METHODS: We examined 44 APSN patients with primary APS and 90 patients with LN: 57 with secondary APS, 33 with antiphospholipid antibodies (APA) without history of thrombosis. In addition to clinical and immunological examination, detection of serological APS markers, morphological examination of renal tissue and ultrasound dopplerography (USDG) of the renal vessels were made (in some patients) for assessment of the condition of intrarenal vascular bed. RESULTS: In patients with primary APS, renal disorder and secondary APS in LN frequency of arterial thrombosis doubles that of venous ones. Renal disorder irrespective of a clinical APS form (primary, secondary) combines with affection of the CNS, heart and skin (livedo). This correlates with frequency of arterial thrombosis. In patients with primary APSN rate of arterial hypertension (AH), especially severe, and renal dysfunction is higher than in LN with APS while this group is characterized by more severe proteinuria, microhematuria and higher incidence of nephrotic syndrome. A direct correlation exists between the incidence of arterial thrombosis and severity of AH, between AH and renal ischemia by USDG. Morphologically, glomerulosclerosis, marked arteriolosclerosis and diffuse interstitial sclerosis occur more often in patients with primary APSN compared to LN patients with APS. CONCLUSION: In primary and secondary (in SLE) APS combination of APSN with impairment of the CNS, heart and skin, correlation of its basic clinical manifestations with arterial thrombosis allow us to single out a special clinical variant of APS manifesting with generalized ischemic lesions of the organs as a result of arterial/arteriolar thrombosis. Irrespective of its nature, APSN has common characteristic features--combination of AH, persistent renal dysfunction and transitory hypercreatininemia--correlating with development of arterial thrombosis; therefore, this pathology can be considered as a variant of thrombotic vascular lesion of the kidneys.     

Prevalence of antiphospholipid and antiplatelet antibodies in human immunodeficiency virus (HIV)-infected Chilean patients

Antiphospholipid (aPL) and antiplatelet (aPlt) antibodies, found in patients with autoimmune diseases, are also detected in infectious diseases. The purpose of this study was to examine the prevalence of these antibodies in HIV patients and to evaluate an association of these antibodies with thrombocytopenia and/or thrombosis. Sixty-three HIV-seropositive patients and 52 normal controls were studied. Anti-cardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies were determined and the lupus anticoagulant (LA) test was performed. Antiplatelet antibodies (aPlt) were also determined. Seven out of 63 (12.7%) HIV patients were positive for aCL, four of 63 (6.3%) for anti-beta(2)GPI, and five of 63 (7.9%) for aPT. No patients studied were LA positive. Six out of 63 (9.5%) patients were positive for aPlt. One of them showed weak reactivity for GPIb-IX. The platelet count of patients (202+/-63 x 10(3) platelets/microL) was significantly lower than in the controls (343+/-6 x 10(3) platelets/microL) (P<0.001). There was no correlation between the presence of aPL and/or aPlt and thrombocytopenia. Of the HIV-infected patients, 22.2% presented aPL and 9.4% aPlt antibodies. In this study, the presence of aPL and aPlt antibodies was not associated with the development of thrombosis and/or thrombocytopenia.     

Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid arthritis

Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-beta(2)GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further.     

Clinical and morphological characteristics of lupus nephritis in systemic lupus erythematosus with antiphospholipid syndrome

AIM: To ascertain clinical and morphological features of lupus nephritis (LN) in systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Immunological markers of SLE and APS, clinical picture, urine indices were examined in 138 patients with SLE, APS and renal dysfunction. RESULTS: LN associated with APS is characterized with marked arterial hypertension, such patients had arterial thromboses more frequently than patients with isolated LN. Patients with anticardiolipin antibodies have arteriolosclerosis, in APS - diffuse interstitial sclerosis. CONCLUSION: Renal impairment in SLE may run not only with LN but also with thrombotic microangiopathy modifying clinical symptoms and course of the disease.     

Hemostasis in patients with rheumatoid arthritis

AIM: To study hemostasis with reference to rheumatoid arthritis (RA) activity, extraarticular manifestations and vascular damage. MATERIAL AND METHODS: We studied hemostasis in 104 RA patients. The following parameters were tested: partial thromboplastin time activation (PTTA), fibrinolytic activity (FA), prothrombin index, lupus anticoagulant (LA), mean platelet volume (PV), antibodies against cardiolipin (aCL) and antibodies against beta2-glycoprotein 1 (alphabeta2-GP1). The disease activity index was estimated by DAS-28 including tender and swelling joints count, erythrocyte sedimentation rate and disease global activity rated by the patient. RESULTS: We found out an increased number of platelets in 54.4%, prolongation of FA and PTTA in 72.5 and 12.5% patients. The rest blood coagulation tests were normal in most the examinees. The LA antibodies were absent, while aCL and alphabeta2-GP1 antibodies were identified in 10.6 and 14.4%, respectively. The number of platelets increased while hemoglobin decreased in relation to higher disease activity and PV was significantly lower in patients with extraarticular manifestations. No significant influence of vascular damage or comorbidities on hemostasis was found. CONCLUSION: No relation was established between coagulation factors and the disease activity except for increased number of platelets in patients with higher activity and lower PV in patients with extraarticular manifestations. However, patients with aCL and alphabeta2-GP1 need constant monitoring because of the risk to develop thrombosis.     

Risk factors for central nervous system involvement in systemic lupus erythematosus

We investigated risk factors for central nervous system (CNS) involvement in systemic lupus erythematosus (SLE), in 32 such patients individually matched 1 : 3 to 96 control SLE patients without CNS events. Univariate analysis showed that CNS involvement was significantly associated with the antiphospholipid syndrome (APS) as well as its features: arterial thrombosis, recurrent fetal loss, livedo reticularis and IgG anticardiolipin (aCL) antibodies in high titres. Other potential associations included cutaneous vasculitic lesions, thrombocytopenia, positive ANA, anti-SS-B/La and low serum levels of C(3) and C(4) complement components, while articular manifestations and discoid rash were significantly less common in patients with neuropsychiatric (NP) disease. In multivariate modeling, CNS involvement was strongly associated with cutaneous vasculitic lesions OR 33, 95% CI 1.5-720) and arterial thromboses (OR 13, 95%CI 0.82-220), and negatively related to the presence of articular manifestations (OR 0.015, 95%CI 0.00-0.17) and discoid rash (OR 0.004, 95%CI 0.00-0.35). Associations with APS-related arterial thromboses and vasculitis point to the importance of arterial vascular pathophysiology in the pathogenesis of NP disease in SLE. Patients with articular manifestations and discoid rash are at very low risk of NP events. Patients with an adverse SLE disease profile may require closer observation and may be the target group for studying pre-emptive interventions.     

Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestations

BACKGROUND: We assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases. MATERIALS AND METHODS: Anti-PAF, anticardiolipin (aCL), antibeta2 glycoprotein I (antibeta2GPI) and antiphosphatidylcholine (anti-PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme-linked immunosorbent assay (ELISA) was developed for determining anti-PAF antibodies in a bovine serum-free fashion. RESULTS: The ELISA showed high specificity. Homologous inhibition experiments showed 60-70% inhibition. Anti-PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL- patients and 3/30 scleroderma patients. Anti-PAF antibodies were significantly associated with anti-PC antibodies (odds ratio [OR] 12. 7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or antibeta2GPI. Three SLE/aCL+ patients and five SLE/aCL- patients had clinical manifestations characteristic of APS. All these patients had anti-PAF antibodies, while none had high titres of aCL or antibeta2GPI antibodies and only one had anti-PC antibodies. Among the combined APS and SLE groups, the presence of anti-PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and antibeta2GPI antibodies. CONCLUSIONS: Anti-PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti-PAF antibodies without other antiphospholipid specificities.     

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.