抗磷脂血栓综合征

目的:了解抗磷脂抗体(APA)与抗磷脂血栓综合征(APL-T)相关性,进一步探讨APL-T血栓发生机制。方法:采用 ELISA检测ACA(IgG,M,A),PTT-LA检测LA,APTT /-APC检测APC-R。结果:20例患者符合 APL-T诊断。根据病因分类:14/100例SLE为继发性 APL-T;6/16例“原因不明”血栓与习惯性流产为原发性APL-T。根据抗体分类:12/20例LA阳性为狼疮抗凝因子血栓综合征(LA-T);12/20例ACA阳性为抗心磷脂抗体血栓综合征(ACA-T)。根据临床症状分类:7/20例静脉血栓为Ⅰ型,3/20例脑梗塞为Ⅱ型;1/20例静脉血栓合并脑梗塞,习惯性流产为Ⅳ型(混全型);9/20例习惯性流产为Ⅴ型APL-T。APL-T患者LA阳性率(12/20,60％)明显高于正常对照组(NC组0/20,0%)。患者ACA-IgG,M与NC组比较有显著性差异(P<0.05);APCR在APL-T患者中阳性率(14/20,70％)明显高于NC组(l/20,5％);LA阳性组中的APCR阳性率(10/11,90.9％)明显高于LA阴性组(l/11,9％),ACA阳性组的APCR阳性率(7/11,63.3％)与ACA阴性组(4/11,36.36％)比较有显著性差异。结论:APA与APCR密切相关,APL-T中血栓发生率与APA以及APCR存在明显相关性,说明APA对PC途径的抑制引起获得性APCR可能是APL-T血栓发生的重要原因,故可将APA作为血栓危险性增加的标志物。     

系统性红斑狼疮患者获得性活化蛋白C抵抗现象与抗磷脂抗体的检测

目的 :通过检测系统性红斑狼疮 (SLE)患者获得性活化蛋白C抵抗 (APCR)和抗磷脂抗体的发生率 ,探讨APCR与SLE患者血栓形成的相关性 ,以及SLE患者血栓形成中 ,APCR与抗磷脂抗体的相关性。方法 :采用APC -APTT法 ,dRVVT -LA法 ,ELISA法及PCR_酶切法分别对 30例SLE患者和 30例正常对照进行APCR及狼疮抗凝物 ,抗心磷脂抗体和FVLeiden突变检测。结果 :SLE病人APCR阳性率 (14/30 ,46 .6 7% )明显高于正常对照组 (1/30 ,3.3% ,P <0 .0 0 5 )。SLE患者无一例FVLeiden突变。APCR阳性患者中血栓发生率 (6 /14,42 .85 % )明显高于APCR阴性患者 (1/16 ,6 .2 5 % ,P<0 .0 5 )。狼疮抗凝物阳性患者中血栓发生率 (6 /12 ,5 0 % )明显高于其阴性患者 (2 /18,11.1% ,P <0 .0 5 )。结论 :获得性APCR和狼疮抗凝物均是SLE患者合并血栓形成的危险因素之一 ,但获得性APCR的发生与抗磷脂抗体的存在无关 ,表明获得性APCR的发生并非抗磷脂抗体抑制蛋白C通路导致凝血异常及致血栓形成的唯一途径。     

习惯性流产与抗活化的蛋白C的研究

目的:了解抗活化的蛋白C(APC)在习惯性流产(RSA)患者中的发生情况,并进一步探讨APCR引起胎盘血管微小血栓形成并进而引起RSA的发生机制。方法:采用APC-KPTT法,ELISA法和PTT-LA法分别对16例RSA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,采用一期法检恻FVⅦ:C,胶乳凝集法检测D-Dimer。结果:16例RSA患者共8例抗磷脂抗体(APA)阳性,其中4例LA阳性,2例ACA阳性,2例LA、ACA同时阳性,阳性率(50%)明显高于NC组(0/20)(P<0.005),APCR阳性率为50％,明显高于NC组(5%)(P<0.005)。APA阳性组APCR阳性率(87.5%)明显高于NC组(5%)(P<0.005)FVⅡ:C及D-Dimer阳性率均明显高于NC组(P<0.001及P<0.05)。APA阴性组APCR阳性率(12.5%)与NC组无显著性差异(P>0.05)FVⅡ:C明显高于NC组(P0.05),相关分析显示,APA阳性组APCR发生率(87.5％)明显高于地APA阴性组(12.5%)(P<0.005)。结论:习惯性流产患者胎盘血管发生血栓一方面由于患者体内处于高凝状态,另一方面由于APCR在习惯性流产患者中有较高的发生率且与APA有明显相关性,APCR可能是引起胎盘微血栓形成并引起习惯性流产的主要原因之一。     

狼疮性肾炎抗活化蛋白C的测定及意义

目的 :探讨抗磷脂抗体和抗活化蛋白C(APCR)与狼疮性肾炎 (LN)的关系及APCR的可能形成原因。方法 :检测 33例LN和 37例无LN的系统性红班狼疮 (NLN) ,ELISA检测ACA -IgG、IgM、IgA、PTT -LA检测LA ,APTT±APC检测APCR。结果 :LN组APCR阳性率 5 7 6% ,明显高于NLN组 ( 32 4% ) ;LN组ACA(IgG、IgM )阳性率 42 4% ,明显高于NLN组 ( 18 9% ) ;APCR和IgG -ACA同时阳性LN的发生率 ( 7/ 7)明显高于APCR阳性而IgG -ACA阴性者( 12 / 2 4)。结论 :APCR和ACA在LN有较高的发生率 ,ACA引起的获得性APCR可能是LN的发病机制之一。     

系统性红斑狼疮患者获得性活化蛋白C抵抗现象与抗磷脂抗体的检测

目的：通过检测系统性红斑狼疮（SLE）患者获得性活化蛋白C抵抗（APCR）和抗磷脂抗体的发生率,探讨APCR与SLE患者血栓形成的相关性,以及SLE患者血栓形成中,APCR与抗磷脂抗体的相关性。方法：采用APC－APTT法,dRVVT-LA法,ELISA法及PCR－酶切法分别对30例SLE患者和30例正常对照进行APCR及狼疮抗凝物,抗心磷脂抗体和FV Leiden突变检测,结果：SLE病人APCR阳性率（14／30,46．67％）明显高于正常对照组（1／30,3．3％,P＜0．005）,SLE患者无一例FV Leiden突变。APCR阳性患者中血栓发生率（6／14,42．85％）明显高于APCR阴性患者（1／16,6．25％,P＜0．05）,狼疮抗凝物阳性患者中血栓发生率（6／12,50％）明显高于其阴性患者（2／18,11．1％,P＜0．05）,结论：获得性APCR和狼疮抗凝物均是SLE患者合并血栓形成的危险因素之一,但获得性APCR的发生与抗磷脂抗体的存在无关,表明获得性APCR的发生并非抗磷脂抗体抑制蛋白C通路导致凝血异常及致血栓形成的唯一途径。     

复发性自然流产与抗磷脂血栓综合征相关性探讨

目的 探讨复发性自然流产（RSA）的原因,了解其与抗磷脂血栓综合生(APL-T)关系。方法 采用ELISA法和PTT－LA法对32例复发性流产及20例正常对照进行抗心磷脂抗体（ACA）和狼疮抗凝物（LA）检测。结果 32例RSA患者中17例APA阳性,阳性率（53．1％）明显高于对照,其中LA阳性率为28．1％,亦明显高于对照。8例诊断为抗磷脂血栓综合征。结论 APA中之LA可能是RSA发生的重要原因,对不明原因的复发性自然流产可考虑为抗磷脂血栓综合征。     

14例恶性抗磷脂综合征病例报道及临床分析

目的: 恶性抗磷脂综合征(catastrophic antiphospholipid syndrome, CAPS),即Asherson综合征,是一种以累及多系统、脏器、组织的多发血管内血栓,高滴度的抗磷脂抗体和高死亡率为特征的一种抗磷脂综合征(antiphospholipid syndrome, APS)亚型。本文分析CAPS的临床表现、实验室检查及治疗,以增加对该病的认识及诊治水平。方法: 回顾性分析APS上海数据库的14例CAPS患者的临床资料并进行描述性统计分析。结果: 14例患者中12例符合2003年第10届抗磷脂抗体国际会议中通过的CAPS分类标准中的确诊APS,2例符合APS可能,其中原发性APS有3例,11例继发于系统性红斑狼疮(systemic lupus erythematosus,SLE)。感染是最常见的发病诱因,其次是狼疮活动和外科手术。临床事件中,动脉血栓最好发的部位为脑和肺,静脉血栓最常见于四肢静脉。抗心磷脂抗体(anticardiolipin antibody, aCL)、抗β2糖蛋白1抗体(anti-β2 glyeoprotein Ⅰ antibody, aβ2GPI)、狼疮抗凝物(lupus anticoagulant, LA)均阳性的患者占54.55%,血小板减少和血红蛋白降低发生于大部分的CAPS患者,其中大多证实为溶血性贫血。死亡病例6例,抗凝药物、激素、静脉注射丙种球蛋白和/或血浆置换的三联疗法可以改善患者的预后,合并SLE和微血管病性溶血性贫血的患者分别可以使用环磷酰胺和利妥昔单抗。结论: CAPS是急性发生的以大量微血栓形成及高抗磷脂抗体滴度为特点的危重症,可以导致多脏器功能衰竭,因本病预后差,及时的诊断和积极的治疗是改善预后的关键。     

564例抗磷脂抗体检测的临床意义

目的总结抗心磷脂抗体(ACA)、狼疮抗凝物(LA)、活化蛋白C抵抗性(APCR)检测与脑梗死、习惯性流产、系统性红斑狼疮(SLE)、深静脉血栓等血栓相关性疾病之间的关系及其临床意义。方法采用APIT-LA法筛选LA;酶联免疫吸附试验(ELISA)法检测ACA—IgG、IgM、IgA;活化蛋白C抑制比值法检测APCR。结果在检测的564例患者中,ACA—IgG、IgM、IgA的阳性率分别为30％、24％和11％,LA的阳性率为6．5％,APCR阳性率为7．9％。其中脑梗死64例,ACA—IgG、IgM、IgA的阳性率为14％,APCR的阳性率为7．8％,未发现LA阳性的病例。265例习惯性流产的患者中,ACA—IgG、IgM、IgA阳性率分别为19％、18％和3％,LA阳性率2．7％,APCR阳性率5．8％。171例的SLE患者中,ACA—IgG、IgM、IgA的阳性率分别为35％、25％和18％,LA阳性率8．8％,APCR阳性率为6％。其他原因不明的血栓性疾病患者64例,ACA—IgG、IgG、IgA的阳性率分别为78％、55％、22％,LA阳性率为30％,APCR的阳性率为23％。结论ACA、LA、APCR的检测对SLE、脑梗死、习惯性流产,尤其是原因不明的血栓性疾病患者的诊断和发病机制研究有重要价值。     

Factor V Leiden mutation in one family of Chinese origin

Objective　To investigate the factor V Leiden mutation associated with activated protein C resistance (APCR) in Chinese. Methods　Thirty “normal' individuals and twenty patients with thrombotic disease from Chinese Han Nationality were studied with APTT±APC, PCR followed by MnLI restriction enzyme analysis,PCR based direct sequence-specific primers (PCR-SSP) and DNA sequence analysis. Results　In one healthy control, the activated protein C (APC) sensitivity ratio (SR) was found to be significantly lower (0.8) than that in other normal control (&gt;2.0). This individual was identified to be heterozygous for FV Leiden mutaiton (Arg506-Gln). His grand-uncle, father, brother and son were also identified to be heterozygous for FV Leiden. The APC resistance was found in 3 other cases of thrombotice diseases, but with no FV Leiden mutation. Conclusion　This is the first four generations family case of FV Leiden mutation associated with APCR reported within Chinese ethnic population. It is note-worthy that more FV Leiden or whether other gene defects may be associated with APC resistance and acquired APCR causing thrombosis in Chinese population.     

系统性红斑狼疮患者中活化蛋白C抵抗的测定及临床意义

 目的探讨系统性红斑狼疮（SLE）患者中活化蛋白C抵抗（APCR）现象及其临床意义。方法分别检测加活化蛋白C（APC）和不加APC的血浆的凝血时间CT1和CT2,计算CT2CT1,规定CT2CT1≤1.8为APCR阳性,≥2.0为APCR阴性。结果SLE患者中APCR阳性率为57.5%,且APCR阳性者均存在血栓所致系统损害。APCR阳性组中狼疮肾炎的发生率明显高于APCR阴性组,而免疫球蛋白G型抗心磷脂抗体（ACA-IgG）阳性组与ACA-IgG阴性组中各系统损害的发生率无明显差异,但APCR、ACA-IgG均阳性的患者均存在动脉或静脉血栓。APCR与反映血栓形成指标D-二聚体和纤维蛋白原、反映肾脏病变程度指标24 h尿蛋白定量、自身抗体（抗核抗体、抗双链DNA抗体和抗ENA抗体谱）均无相关性。结论APCR可能是SLE患者诱发血栓的危险因素之一,ACA通过对蛋白C系统的间接抑制作用协同参与血栓形成过程,APCR的检测对预测SLE患者并发血栓可能更有价值。     

抗磷脂综合征57例临床分析

目的 分析抗磷脂综合征（antiphospholipid syndrome,APS）的临床表现、诊断及治疗,以提高本病的诊治水平.方法 回顾性分析2004-2013年在本院诊断明确的57例APS患者的临床特征和免疫学特点.结果 57例中男性14例（24.6％）,女性43例（75.4％）,确诊时平均年龄（37±14）岁;原发性APS 21例（36.8％）,继发性APS 36例（63.2％）.血栓发生率71.9％,血栓复发率41.5％,原发性APS的血栓复发率高于继发性APS（P＜0.05）;病态妊娠发生率63.3％.本组患者65.4％抗心磷脂抗体（anticardiolipin antibodies,ACL）阳性,71.9％抗β2-糖蛋白Ⅰ抗体阳性,42％血小板减少.在确诊APS前,43.9％被诊断为血栓事件,33.3％被诊断为自身免疫性疾病,8.8％被诊断为血小板减少.结论 APS临床表现以血栓形成、病态妊娠为主,免疫学特点为高滴度的ACL和（或）抗β2-糖蛋白Ⅰ抗体阳性.APS临床症状多样化导致其误诊率较高.     

The relationship between lupus anticoagulants and antibodies to phospholipid

The relationship between lupus anticoagulants and antibodies directed against negatively charged phospholipids, as measured by an enzyme-linked immunosorbent assay, was explored in a series of plasma samples from 100 patients with well-characterized lupus anticoagulants. Only 73% of the patients had detectable IgG, IgM antibodies, or both, to one or more of four phospholipids. Of these patients, 29% had IgG-type antibodies only, 56% had both IgG and IgM antibodies, and 15% had IgM antibodies only. Of the 100 patients, 19% had a history of thrombosis, 8% had a history of spontaneous abortion, and 6% had a history of seizure disorder. These complications occurred in the presence (80%) and absence (20%) of detectable antiphospholipid antibodies. Drug-related antibodies were observed in 34 patients; of these, 71% had detectable anti-phospholipid antibodies and 24% had a history of thrombosis. There were ten patients with lupus anticoagulants associated with infections; none of these patients had a history of thrombosis. The results indicate that antiphospholipid antibodies are not present in all patients with lupus anticoagulants, that the presence of antiphospholipid antibodies in patients with lupus anticoagulants does not increase the risk of thrombosis in these patients, and that drug-related antibodies are associated with an increased risk of thrombosis. Lupus anticoagulants and antiphospholipid antibodies seem to define two distinct but related patient populations, each associated with an increased risk of thrombosis.     

抗磷脂抗体相关性复发性流产的诊治:附75例抗磷脂综合征患者妊娠期用药和结局分析

Recurrent spontaneous abortion is one of the common complications in women of childbearing age during pregnancy. The immune factor accounts for a large proportion of many causes. Antiphospholipid antibody syndrome is the most common type of acquired thrombophilia disease. Autoimmune di-seases that cause thrombosis and obstetric complications under the action of antibodies are also the most common type of immune-related recurrent abortion. At present, there is no unified opinion on the treatment of this disease, especially the treatment of immunoglobulins and other drugs like glucocorticoid. Here we reviewed the progress of diagnosis and treatment of antiphospholipid antibody-related recurrent abortions and retrospectively analyzed and summarized the drug regimens and pregnancy outcomes of this disease with pregnancy patients in our hospital. A total of 75 patients were included. According to their clinical manifestations and laboratory results, these patients were basically divided into two categories:classical antiphospholipid syndrome and non-classical antiphospholipid syndrome. The latter was further divided into serum-negative antiphospholipid syndrome and antiphospholipid antibody-related recurrent abortion patients based on their clinical manifestations and antiphospholipid antibody results. The patients were divided into four categories:aspirin + hydroxychloroquine, aspirin + low molecular weight heparin, aspirin + low molecular weight heparin + hydroxychloroquine, aspirin + hydroxychloroquine + low molecular weight heparin + low dose glucocorticoids. Among them, aspirin + hydroxychloroquine + low molecular weight heparin + low-dose glucocorticoid treatment regimen was most commonly used. Most of the patients who received the above different treatment regimens achieved full-term infants, and a small number of patients had adverse pregnancy outcomes, such as premature delivery, placental abruption, eclampsia, and fetal malformation. And adverse pregnancy outcomes also occurred in this group. It might be related to the severity of the disease and the potential adverse effects of maternal fetal. However, further statistical analysis is needed for the risk factors affecting the pregnancy outcome of this part of patients.     

抗磷脂综合征61例临床分析

目的分析抗磷脂综合征(APS)的临床特点、诊断和治疗方法,提高对本病的认识。方法对诊断明确、资料完整的61例APS患者的临床特点进行回顾性分析。结果61例患者中,男女比为1:3.1。共有原发性APS 10例和继发性APS51例,在51例继发性APS中,继发于自身免疫性疾病者48例(94.1％),其中系统性红斑狼疮33例(64.7％)。61例患者中有49例发生血栓事件,共93例次,以消化系统(21例次,22.6％),肺部(19例次,20.4％),神经系统(17例次,18.3％)和下肢深静脉血栓(16例次,17.2％)多见,另外还包括肾上腺和冠脉血栓等。37例有生育史的女性患者中17例(45.9％)有病态妊娠史。61例患者中有47例(77.0％)抗心磷脂抗体(ACL)阳性,38例(62.3％)狼疮抗凝物(LA)阳性,二者之间存在相关性(p<0.01)。结论APS以血栓形成、病态妊娠和ACL和/或LA阳性为特点;血栓好发部位为消化系统、肺、神经系统和深静脉。ACL、LA和临床表现之间存在显著相关性(P<0.01),但LA与临床表现的相关性大于ACL。抗血小板和长期抗凝治疗是主要的治疗方法。     

抗磷脂综合征患者血栓事件的危险因素分析

目的：探讨影响抗磷脂综合征（antiphospholipid syndrome, APS）患者血栓事件发生的危险因素。方法：回顾性分析北京大学人民医院收治的61例APS患者血栓事件的发生特点,评价血栓事件与患者临床及免疫学指标的相关性,包括性别、年龄、有无血小板减少、吸烟、高血压、糖尿病、高脂血症和抗磷脂抗体等。结果：70.49% APS患者发生血栓事件,其中动脉血栓发生率36.67%,静脉血栓发生率39.34%,下肢静脉血栓和脑梗塞最常见,分别占37.7%和24.59%,其次为肺栓塞、血栓性微血管病、肾梗死和脾梗死。抗心磷脂抗体阳性和高血压分别是静脉和动脉血栓事件的独立危险因素。结论：抗心磷脂抗体阳性者易发生静脉血栓,而合并高血压的APS患者易发生动脉血栓。     

40例深静脉血栓形成患者血浆LA水平的测定

目的 了解深静脉血栓形成患血浆狼疮抗凝物（LA）水平的变化，探讨静脉血栓形成的发生机制。方法 用APTT法检测40例深静脉血栓患与40例健康的LA。结果 深静脉血栓患组LA阳性率（12.5%)显高于对照组（P＜0.05)。结论 LA可能是静脉血栓形成的危险因素之一。     

新疆地区动脉血栓形成患者抗活化蛋白C及FV Leiden突变的调查

目的研究抗活化蛋白C（activated protein C resistance，APCR）现象和FV Leiden在新疆正常人群、血栓患者中的发生情况。方法对414例正常体检者（N）和79例脑梗死患者组（CT）及46例心肌梗死患者组（MI），用APCR法进行APCR敏感比（n—APC—SR）（〈0．68）和APCR阳性率（〈2．0为阳性）测定，用多聚酶链反应-限制性内切酶长度多态性（PCR—RFLP）分析及DNA序列分析对以上标本APCR阳性者做FV Leiden突变和凝血酶原G20210A位基因突变的检测的分析。结果APCR发生率正常对照组为6．28％，其APCR发生率在哈萨克族、维吾尔族、回族、汉族中分别是12％、8．4％、8．35％及4．8％，正常人APCR发生率在哈萨克族较高，且各少数名族与汉族APCR发生率差异有统计学意义（P〈0．05）。脑梗死病例组的APCR发生率为11．39％，心肌梗死病例组的APCR发生率为8．70％；两组间以及两组APCR发生率分别与对照组比较差异有统计学意义（P〈0．05）。各组人群中均未检出FV Leiden 1691 G—A突变杂合子以及凝血酶原G20210A位基因突变。结论APCR现象在新疆地区正常人少数民族中有较高的发生率，其分布与人种、地域有关。未检出FV Leiden，和凝血酶原G20210A位突变。因此，FV Leiden突变不是新疆地区人群动脉血栓发病的主要危险因素.     

50例妊娠合并抗磷脂综合征患者的疗效观察

目的:观察低分子肝素联合阿司匹林运用于妊娠合并抗磷脂综合征的治疗效果。方法:将50例确诊为单纯性抗磷脂综合征孕妇,随机分为两组各25例,观察组低分子肝素联合阿司匹林用药,对照组单用阿司匹林,分别观察两组治疗前后的抗心磷脂体(ACA)和狼疮抗凝物(LA)的变化,并且对妊娠结局和新生儿Apgar分数进行比较。结果:治疗后两组活产率、ACA和LA抗体清除率均具有显著性差异(P<0.05);两组在新生儿Apgar评分方面无显著性差异(P>0.05)。结论:低分子肝素联合阿司匹林治疗抗磷脂综合征安全有效。     

The antiphospholipid antibody syndrome research in patients with retinal venous occlusion

BACKGROUND: The antiphospholipid antibody syndrome (APAS) is a condition associated with abnormal thrombosis and the presence of anticardiolipin antibodies (aCL). METHODS: Thirty-two patients (20 male and 12 female) aged between 29 and 75 years (mean +/- SD: 56.4 +/- 12.34) with retinal venous occlusive disease were studied. All patients with a history of venous occlusive disease within the previous 8 months were included in the study. Diagnoses were made by fundus examination and fundus fluorescein angiography (FFA). Anticardiolipin IgM and IgG antibodies, antinuclear antibodies (ANA), and IL-1beta were investigated in all patients. RESULTS: Neither aCL-IgM nor aCL-IgG was observed as positive in this group. Only four patients were found to be ANA positive. However, serum levels of IL-1beta were higher than those of controls (p <0.001). Mean IL-1beta was found to be 18.06 +/- 3.39 pg/mL (mean +/- SE), respectively. IL-1beta levels were found to be significantly different from those of controls (2.7 +/- 0.68 pg/mL) (p <0.001). In this study, antiphospholipid antibody positivity was not determined in any patients. CONCLUSIONS: As a result, IL-1beta level appears higher in retinal venous occlusive disease. This cytokine measurement might be used as a diagnostic indicator for venous occlusive disease.