Detection of antiphospholipid antibody levels in normal pregnant women by chemiluminescence immunoassay and comparison between different trimesters / 中华围产医学杂志

Objective:Chemiluminescence immunoassay was used to detect the levels of anticardiolipin antibody (aCL) -IgA/IgG/IgM and anti-β2-glycoprotein Ⅰ antibody (aβ2GPⅠ) -IgA/IgG/IgM in healthy non-pregnant and pregnant women to explore the changes of antiphospholipid antibody in different pregnancy periods.Methods:This prospective study was conducted in Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, involving normal pregnant women who underwent prenatal examination and healthy non-pregnant women with no history of adverse pregnancy who underwent progestational eugenic health examination from April 2020 to August 2021. The levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM were detected using BIO-FLASH chemiluminescence immunoassay analyzer and P95 as well as P99 were calculated, respectively. The difference in the six data between non-pregnant and pregnant women was compared using Mann-Whitney U test. Kruskal-Wallis H test was used to compare the change of each antibody in different pregnancy periods and Spearman correlation was used to analyze the correlation between different trimester and the levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM. Results:A total of 454 cases met the inclusion criteria, and 435 cases were included in the analysis after excluding 19 cases, among them 110 were non-pregnant women and 325 were pregnant women, including 110 cases in the first trimester (≤13 +6 weeks), 110 cases in the second trimester(14 +0-27 +6 weeks), and 105 cases in the third trimester (≥28 weeks). P99 value of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM in the non-pregnant women were 7.31, 14.70, 7.92, 3.58, 13.60, and 4.95 CU, which in the pregnant women were 5.90, 12.78, 5.70, 1.60, 10.65, and 3.90 CU, and were all lower than the cut-off value of 20 CU that given by the analyzer manufacturer. The levels of aCL-IgA/IgG/IgM, and aβ2GPⅠ-IgG/IgM in the pregnant women were significantly decreased comparing with the non-pregnant women [aCL-IgA: 1.90 CU (1.40-2.70 CU) vs 2.90 CU (2.20-3.83 CU), Z=－7.14; aCL-IgG: 3.00 CU (2.20-4.50 CU) vs 6.10 CU (4.20-7.83 CU), Z=－10.26; aCL-IgM: 1.40 CU (1.10-2.30 CU) vs 2.65 CU (2.08-3.73 CU), Z=－8.87; aβ2GPⅠ-IgG: 3.50 CU (2.60-4.90 CU) vs 4.75 CU (3.60-5.93 CU), Z=－5.45; aβ2GPⅠ-IgM: 0.70 CU (0.50-1.20 CU) vs 1.00 CU (0.60-1.53 CU) , Z=－3.73; all P<0.001]. The aCL-IgA level in the third trimester was higher than those in the first and second trimester (both P<0.05). The levels of aCL-IgG/IgM in the second trimester and aβ2GPⅠ- IgG in the second and third trimesters were significantly decreased than those in the first trimester (all P<0.05). Spearman analysis showed that aCL-IgG/IgM, aβ2GPⅠ-IgA/IgM had no significant correlation with the pregnancy period (the first, second and the third trimester) (all P>0.05). However, a weak correlation between the aCL-IgA, aβ2GPⅠ- IgG and the pregnancy period was observed ( r=0.28 and－0.49, both P<0.001) Conclusions:P99 value of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM levels in normal pregnant women and non-pregnant women are lower than the cut-off value of 20 CU given by the analyzer manufacturer. The levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgG/IgM during pregnancy are lower than those before pregnancy and fluctuate with the pregnancy period, but have no significant correlation with the pregnancy period. The clinical diagnosis of antiphospholipid syndrome should be made according to the cut-off values of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM determined by each laboratory.

Retinal ischemia as the first manifestation of antiphospholipid antibody syndrome / Isquemia retiniana como primeira manifestação da síndrome do anticorpo antifosfolipídio

ABSTRACT Antiphospholipid antibody syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and by gestational morbidity (recurrent fetal losses) in the presence of antiphospholipid antibodies. We report the case of a 38-year-old woman who was diagnosed with primary APS from thromboembolic abnormalities in the retinal periphery that led to retinal ischemia. The aim of this study is to share with physicians and medical undergraduates an atypical manifestation of the syndrome that is the most common acquired thrombophilia, that should be part of the diagnostic routine of all clinical specialties.

RESUMO A síndrome do anticorpo antifosfolipídio (SAAF) caracteriza-se pelo desenvolvimento de tromboses venosas e/ou arteriais e pela morbidade gestacional (perdas fetais recorrentes) na presença de anticorpos antifosfolipídicos. Foi relatado o caso de uma paciente de 38 anos que foi diagnosticada com SAAF primária, a partir de alterações tromboembólicas na periferia da retina, que levaram à isquemia retiniana. O objetivo desse estudo é compartilhar com médicos e acadêmicos de medicina uma manifestação atípica da síndrome que é a trombofilia adquirida mais comum, devendo fazer parte da rotina diagnóstica de todas as especialidades clínicas.

Anticardiolipin antibodies and recurrent spontaneous abortion in Brazilianwomen / Anticardiolipin antibodies and recurrent spontaneous abortion in Brazilianwomen

Aims: To determine the frequency of anti-cardiolipin antibodies (aCL) in women with previous history of recurrent spontaneous abortion (RSA).Methods: Medical records from pregnant women seen from April 2005 to December 2008 at the High-Risk Pregnancy Unit at the Hospital de Base from FUNFARME (Fundação Faculdade Regional de Medicina), in São José do Rio Preto, São Paulo, Brazil, were revised. Patients olderthan 18 years who had at least two spontaneous abortions and who were tested for aCL wereincluded in the study. Data on maternal age, number of miscarriages and the results of serological tests for aCL were recorded. The exact Fisher's test was used to compare the results. A p value less than 0.05 was considered significant.Results: During the study period a total of 294 pregnant women were seen, from whom 44 consecutive women fulfilled the inclusion criteria. The overall mean age was 33.8±5.4 years (range: 22 to 44; median: 34). Eighteen (40.9%) patients were reagent for aCL and 26 (59.1%) non-reagent,and the difference between their mean age was not statistically significant (reagent: 34.6±5.8 years; non reagent: 33.2±5.2 years, p=0.4001). Fourteen (77.8%) patients presented IgM aCL and six (33.2%), IgG aCL. Two patients (11%) were reagent for both IgM and IgG aCL. In the most of cases the aCL antibody titers were compatible with low risk for pregnancy morbidity. The number of abortions ranged from two to six. The average number of abortions among those reagent for aCL was 3.5±1.1 and in those non-reagent was 2.9±1.1 (p=0.0813). Conclusions: The frequency of aCL was elevated among patients with a history of RSA,especially those having higher number of fetal losses. Among women with at least two spontaneousabortions, the mean number of abortions was not significantly different between those reagent for aCL and those non reagent.

Objetivos: Avaliar a frequência de anticorpos anticardiolipina (aCL) em mulheres comhistória prévia de aborto espontâneo recorrente (AER).Métodos: No período de abril de 2005 a dezembro de 2008 foram avaliados os dados deprontuários de gestantes atendidas no Ambulatório de Gestação de Alto Risco do Hospital de Baseda Fundação Faculdade Regional de Medicina (FUNFARME), em São José do Rio Preto, SãoPaulo, Brasil. Foram incluídas neste estudo pacientes com idade acima de 18 anos que tiveram pelomenos dois abortos espontâneos e foram avaliadas para aCL. O teste exato de Fisher foi usado paracomparar os resultados. Valor de p menor que 0,05 foi considerado significante.Resultados: Um total de 294 mulheres gestantes foram avaliadas durante o período doestudo, das quais 44 atendiam aos critérios de inclusão. A média de idade foi 33,8±5,4 anos(variação: 22 a 44; mediana: 34). Dezoito pacientes (40,9%) foram reagentes para aCL e 26 (59,1%)não reagentes, e a diferença entre a média de idade não foi estatisticamente significante (reagentes:34,6±5,8 anos; não reagentes: 33,2±5,2 anos, p=0,4001). Quatorze (77,8%) pacientes apresentaramaCL IgM e seis (33,2%) aCL IgG. Duas pacientes (11%) foram reagentes para ambas as classes deaCL, IgM e IgG. Na maioria dos casos os títulos de anticorpos aCL foram compatíveis com baixorisco para morbidade na gravidez. O número de abortos variou de dois a seis. O número médio deabortos entre as reagentes para aCL foi de 3,5±1,1 e entre as não reagentes foi de 2,9±1,1(p=0,0813).Conclusões: A frequência de aCL foi alta entre as pacientes com história de AER,especialmente entre aquelas que tiveram um maior número de perdas fetais. Entre as mulheres compelo menos dois abortos espontâneos, a média do número de abortos não foi significativamentediferente entre aquelas reagentes e não reagentes para aCL.

Clinical significance of different antiphospholipid antibody isotypes in systemic lupus erythematosus / 中华检验医学杂志

Objective To investigate the prevalence and clinical significance of different subtypes (IgG,IgM and IgA) of anticardiolipin antibodies (aCL) and anti-β2-glycoprotein Ⅰ antibodies (aβ 2GP1),as well as lupus anticoagulant (LA) in systemic lupus erythematosus (SLE).Methods IgG/IgM/IgA,IgG,IgM,IgA aCL and anti-β2GP1 were tested by enzyme-linked immunosorbent assay (ELISA) in 100 patients with SLE (42 patients were diagnosed as secondary antiphospholipid syndrome),44 healthy controls and 32 patients with other connective tissue diseases excluding SLE and antiphospholipid syndrome (APS).Meanwhile,LA was tested by modified Dilute Russell's viper venom time (dRVVT).The correlation between antiphospholipid antibodies and clinical manifestation was analyzed by Spearman correlation analysis.The postiverate of antiphospholipid antibodies in SLE patients,health controls and patients with other connective tissue diseases were compared by chi square test.The concentrations of antiphospholipid antibodies in different groups were compared using independent sample Kruskal Wallis test.The diagnostic efficacy of antiphospholipid antibodies in SLE patients was analyzed by crosstable using clinical diagnosis of APS as gold standard.P ＜ 0.05 was considered statistically significant.Results The prevalence of IgG aCL (x2 =15.031,P ＜ 0.001),IgA/G/M (x2 =11.678,P =0.003) and IgA (x2 =6.17,P =0.036) antiβ2GP1 were significantly higher in patients with SLE than in the other two groups.IgA/G/M (r =0.207,P=0.039),IgG (r=0.230,P=0.021) and IgA (r=0.217,P=0.030) aCL,IgA/G/M (r=0.218,P=0.029) and IgA (r =0.255,P =0.01) anti-β2GP1,as well as LA (r =0.233,P =0.02) were associated with thrombotic events.IgA/G/M anti-β2GP1 (r =0.22,P =0.029) and LA (r =0.254,P =0.011) were associated with pathological pregnancy.23.1％ (6/26) aCL positive SLE patients were IgM and/or IgA aCL positive.53.6％ (15/28) anti-β2GP1 positive SLE patients were IgM and/or IgA antiβ2GP1 positive.In SLE patients,the specificity and sensitivity of IgA/G/M aCL for APS were 98.3％ and 26.2％,respectively.The specificity and sensitivity of IgA/G/M anti-β2GP1 were 84.5％ and 40.5％,respectively.The specificity of at least two isotypes positive for APS (both aCL and anti-β2GP1 were 98.3％),was higher than IgG aCL (94.8％) or anti-β2GP1 (93.1％).The sensitivity of at least one isotype of aCL (47.6％) or anti-β2GP1 (42.9％) positive for APS were higher than IgG aCL (40.5％)and anti-β2GP1 (21.4％).Conclusions IgG and IgM aCL together would be better than IgA/G/M aCL for APS screening.IgA/G/M anti-β2GP1 would be better for APS screen due to higher sensitivity and strong association with thromboembolic events and pathologic pregnance.IgA aCL or anti-β2GP1 was associated with thromboembolic events.IgA aCL or anti-β2GP1 would be useful for APS diagnosis in IgG and IgM aCL or anti-β2GPl negative patients.

A meta-analysis of correlation between antiphospholipid antibodies and retinal vein occlusion / 中华眼底病杂志

Objective To evaluate the correlation between antiphospholipid (APLA) antibodies and retinal vein occlusion (RVO).Methods A computerized search was conducted in the Pubmed,Chinese Biological Medicine Database,China National Knowledge Infrastructure,VIP database,Wanfang Database combined with manually searching of literature reference proceedings.The search time was ranged from establishment of each database to August 1st,2012.After the data extraction,quality of RCT was assessed.The meta analysis was performed by Stata 11.0.Results In total,12 case-control studies (1324subjects) that fulfilled the eligibility criteria were included in the meta-analysis involving 505 patients in RVO group and 819 subjects in control group.The odds ratio (OR) and 95％ confidence interval (CI) of APLA,anticardiolipin antibodies (ACA),lupus coagulation inhibitor and RVO were 5.01 and 3.33-7.53,4.38 and 2.38 8.05,1.72 and 0.73-4.04,respectively.The OR and 95％ CI of APLA,ACA and central RVO were 4.80 and 2.59-8.88,6.02 and 2.06-17.63,respectively.The OR and 95％ CI of APLA,ACA,lupus coagulation inhibitor and branch RVO were 4.22 and 1.67-10.63,3.69 and 1.32-10.32,2.07 and 0.79-5.41,respectively.Conclusions APLA may increase the rick of RVO,especially ACA has a prediction function to RVO.It is necessary to screening for APLA in RVO patients.

Sneddon's syndrome: case report and review of its relationship with antiphospholipid syndrome / Síndrome de Sneddon: relato de caso e revisão sobre a relação com a síndrome do anticorpo antifosfolipídio

The Sneddon's syndrome is a rare disorder characterized by the occurrence of cerebrovascular disease associated with livedo reticularis. The antiphospholipid syndrome is the most frequent type of acquired thrombophilia, defined by the occurrence of thrombosis or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. Approximately 80% of Sneddon's syndrome patients have an antiphospholipid antibody marker. These antibodies may play a pathogenetic role in some cases of Sneddon's syndrome, and many authors consider these two syndromes as the same entity. Although clinical features of antiphospholipid syndrome and Sneddon's syndrome may overlap, there is a distinction between clinical and laboratory evidence suggesting that these two entities are different diseases. A recent finding of coagulopathies, including elevated levels of coagulation factor VII, decreased levels of protein S, and activated protein C in Sneddon's syndrome patients suggested a possible biological link between the vasculopathy and a primary coagulopathy. Moreover, the clinical course seems to be progressive in Sneddon's syndrome patients and includes increase of disability and cognitive deterioration, more arterial involvement, and the antiphospholipid syndrome shows a more benign course. Both syndromes share clinical and laboratory features, and whether Sneddon's syndrome represents a spectrum of antiphospholipid syndrome remains unclear. Sneddon's syndrome patients have a worse prognosis and may represent a subgroup of patients who demands more rigorous follow-up. It is important to recognize the Sneddon's syndrome, particularly because stroke episodes may be prevented through appropriate treatment.

A síndrome de Sneddon é um distúrbio raro caracterizado pela ocorrência de doença cerebrovascular associada a livedo reticular. A síndrome do anticorpo antifosfolipídio é o tipo mais frequente de trombofilia, definida pela ocorrência de trombose ou morbidade gestacional na presença de anticorpos antifosfolípides persistentemente positivos. Aproximadamente 80% dos pacientes com síndrome de Sneddon apresentam um marcador de anticorpo antifosfolipídio. Esses anticorpos podem exercer um papel fisiopatológico em alguns casos de síndrome de Sneddon, e muitos autores consideram essa síndrome e a síndrome do anticorpo antifosfolipídio a mesma entidade. Apesar de os quadros clínicos das suas síndromes poderem se sobrepor, há evidência clínica e laboratorial distintiva, sugerindo que as duas entidades são doenças diferentes. Um achado recente de coagulopatia, incluindo níveis elevados do fator VII de coagulação, diminuição dos níveis da proteína S, e proteína C ativada em pacientes com síndrome de Sneddon, sugeriu uma possível ligação biológica entre a vasculopatia e coagulopatia primária. Além disso, o curso clínico pareceu ser progressivo em pacientes com síndrome de Sneddon, visto que há aumento de incapacidade e deterioração cognitiva, além de maior envolvimento arterial, enquanto a síndrome do anticorpo antifosfolipídio apresenta um curso mais benigno. Ambas as síndromes compartilham características clínicas e laboratoriais; até qual ponto a síndrome de Sneddon representa um espectro da síndrome do anticorpo antifosfolipídio permanece desconhecido. Os pacientes com a primeira síndrome apresentam pior prognóstico e podem representar um subgrupo de pacientes que requer um seguimento mais rigoroso. É importante reconhecer a síndrome de Sneddon já que os episódios de acidente vascular cerebral podem ser prevenidos com a terapia apropriada.

Analysis on risk factors for deep vein thrombosis after bone trauma / 中华创伤杂志

Objective To investigate the risk factors for deep vein thrombosis (DVT) after bone trauma.Methods The study involved 118 patients with traumatic fractures (traumatic fracture group),21 DVT patients diagnosed by color Doppler (DVT group) and 56 healthy patients (control group).Anti-cardiolipin antibody (ACA) was determined by ELISA method.D-dimer and fibrinogen (Fib) were detected by coagulation analyzer and C-reactive protein (CRP) by rate nephelometry.Results Levels of D-dimer,Fib and CRP in traumatic fracture group were significantly increased,but were lower than those in DVT group.ACA positive rate in DVT group presented significant increase and three patients with positive ACA in traumatic fracture group all suffered from DVT.The positive rates of Fib,D-dimer and CRP in lower limb fracture group,multiple fracture group and pelvic fracture group were higher than those in upper limb fracture group (P ＜ 0.05).Levels of Fib and D-dimer showed gradual rise with growth of age,but their levels in DVT group had different degree of reduction after thrombolytic therapy.Conclusions Positive ACA and enhancement of D-dimer,Fib and CRP are risk factors for DVT after bone trauma.Levels of Fib and D-dimer in patients with bone trauma are related with age and therefore risk of posttraumatic DVT increases with age.

Úlceras de pernas e anticorpos anticardiolipinas / Leg ulcers and anticardiolipin antibodies

Fenômenos pró-trombóticos são descritos em úlceras de perna de diferentes etiologias. Neste trabalho, procurou-se verificar a prevalência de anticorpos anticardiolipina nestes pacientes. Para isso, estudaram-se 151 pacientes com úlcera de pernas e 150 controles, sendo obtidos dados clínicos e títulos de anticorpos anticardiolipina. Os anticorpos anticardiolipina foram detectados em 7,2 por cento do grupo úlcera e 1,3 por cento do grupo controle (p=0.01), todavia, as características clínicas não foram diferentes nos pacientes com e sem anticorpos anticardiolipina.

Prothrombotic phenomena are described in leg ulcers of different etiologies. This work attempts to verify the prevalence of anticardiolipin antibodies in such patients. For this purpose, 151 patients with leg ulcers and 150 control patients were studied and it was obtained clinical data and anticardiolipin antibodies titers. Anticardiolipin antibodies were detected in 7,2 percent of the patients from the ulcer group against 1.3 percent of the patients in the control group (p=0.01). However, clinical characteristics were not different in patients with and without anticardiopilin antibodies.

Auto-anticorpos anti-β2-glicoproteína I e síndrome metabólica / Anti-beta2-glycoprotein I autoantibodies and metabolic syndrome / Anticuerpos anti-β2-glicoproteína I y síndrome metabólico

FUNDAMENTO: A síndrome metabólica (SM) é uma entidade pró-aterogênica. Autoanticorpos tais como β2-glicoproteína I (β2-gpI) podem influenciar o aparecimento de ateromas. Estudos anteriores confirmaram uma associação entre anticorpos IgA anti-β2-gpI e isquemia cerebral, infarto do miocárdio, doença arterial periférica e doença da carótida. OBJETIVO: O objetivo desse estudo de caso-controle foi avaliar uma possível associação entre anticorpos anti-β2-gpI e anticardiolipina (aCL) com SM não-complicada. MÉTODOS: Pacientes com SM sem histórico de eventos vasculares e indivíduos-controle, consistindo em pacientes da Enfermaria de Ortopedia admitidos devido a doenças musculoesqueléticas foram incluídos no estudo. Idade, sexo, etnia, histórico de hipertensão, tabagismo, hipercolesterolemia e diabetes mellitus foram avaliados como fatores de risco em ambos os grupos. Anticorpos IgG, IgM, e IgA anti-β2-gpI e aCL foram detectados através de imunoensaios enzimáticos. RESULTADOS: Um total de 68 pacientes com SM e 82 controles foram estudados. Os pacientes com SM tinham média de idade superior à dos controles (P = 0,001), enquanto homens (P = 0,003; OR 0,31; IC95 por cento: 0,15-0,16) e etnia caucasiana (P = 0,004; OR 0,25; IC95 por cento:0,10-0,60) eram predominantes nos controles. Histórico de hipertensão, hipercolesterolemia e diabetes mellitus foi mais prevalente nos pacientes com SM do que nos controles (P < 0.05). A frequência de anticorpos aCL (todos os isotipos) e do IgG e IgM anti-β2 gpI não diferiu de forma significante nos pacientes com SM e controles. Anticorpos IgA anti-β2-gpI foram significantemente mais frequentes nos pacientes com SM (42,2 por cento) do que nos controles (10,9 por cento) (P < 0,001). O OR ajustado para anticorpos IgA anti-β2-gpI foi 3,60 (IC95 por cento: 1,55-8,37; P = 0,003). CONCLUSÃO: O presente estudo mostra que níveis elevados de autoanticorpos IgA para β2-gpI podem estar independentemente associados com SM.

BACKGROUND: The metabolic syndrome (MetS) is a proatherogenic entity. Autoantibodies to phospholipid cofactors such as beta2-glycoprotein I (beta2-gpI) can influence atheroma appearance. Previous studies confirmed an association of IgA anti-beta2-gpI antibodies with cerebral ischemia, myocardial infarction, peripheral artery disease and carotid disease. OBJECTIVE: This case-control study evaluates a possible association of anti-beta2-gpI and anticardiolipin (aCL) antibodies with non-complicated MetS. METHODS: Cases comprised patients with MetS without history of vascular events; controls included individuals from the Orthopedic Infirmary admitted due to musculoskeletal disorders. Age, sex, race, history of hypertension, smoking, hypercholesterolemia and diabetes mellitus were evaluated as risk factors in both groups. IgG, IgM, and IgA anti-beta2-gpI and aCL antibodies were detected by enzymatic immunoassay. RESULTS: Sixty-eight patients with MetS and 82 controls were studied. Patients with MetS showed mean age higher than controls (P = 0.001), while males (P = 0.003; OR 0.31; 95 percentCI 0.15-0.16) and Caucasian ethnicity (P = 0.004; OR 0.25; 95 percentCI 0.10-0.60) predominated in controls. History of hypertension, hypercholesterolemia and diabetes mellitus were more prevalent in cases than in controls (P < 0.05). The frequency of aCL antibodies (all isotypes) and of IgG and IgM anti-beta2 gpI did not significantly differ in cases and controls. IgA anti-beta2-gpI antibodies were significantly more frequent in MetS patients (42.2 percent) than controls (10.9 percent) (P < 0.001). The adjusted OR for IgA anti-beta2-gpI antibodies was 3.60 (95 percentCI 1.55-8.37; P = 0.003). CONCLUSION: The current study shows that elevated levels of IgA autoantibodies to β2-gpI might be independently associated to MetS.

FUNDAMENTO: El síndrome metabólico (SM) es una entidad pro-aterogénica. Autoanticuerpos tales como β2-glicoproteína I (β2-GPI) pueden influir en la aparición de ateromas. Estudios previos han confirmado una asociación entre anticuerpos IgA anti-β2-GPI y la isquemia cerebral, infarto de miocardio, enfermedad arterial periférica y enfermedad carotidea. OBJETIVO: El objetivo de este estudio de caso-control fue evaluar una posible asociación entre los anticuerpos anti-β2-GPI y anticardiolipina (aCL) con SM complicada. MÉTODOS: Se incluyeron en el estudio a los pacientes con SM sin antecedentes de eventos vasculares y los sujetos control, que consiste en pacientes de la Internación de Ortopedia ingresados debido a enfermedades musculoesqueléticas. Edad, sexo, origen étnico caucásico, antecedentes de hipertensión, tabaquismo, hipercolesterolemia y diabetes mellitus fueron evaluados como factores de riesgo en ambos grupos. Anticuerpos IgG, IgM, e IgA anti-β2-GPI y aCL se detectaron a través de inmunoensayos enzimáticos. RESULTADOS: Un total de 68 pacientes con SM y 82 controles se estudiaron. Los pacientes con SM tenían un promedio de edad superior de los controles (p = 0,001), mientras que los hombres (p = 0,003; OR 0,31; IC95 por ciento: 0,15-0,16) y origen étnico caucásica (p = 0,004; OR 0,25; IC95 por ciento:0,10-0,60) eran predominantes en los controles. Historia de hipertensión, hipercolesterolemia y diabetes mellitus fue más prevalente en los pacientes con SM que en los controles (p < 0,05). La frecuencia de anticuerpos aCL (todos los isotipos) y del IgG e IgM anti-β2 gpI no se distinguió de forma significante en los pacientes con SM y controles. Anticuerpos IgA anti-β2-gpI fueron significantemente más frecuentes en los pacientes con SM (42,2 por ciento) que en los controles (10,9 por ciento) (p < 0,001). El OR ajustado para anticuerpos IgA anti-β2-gpI fue 3,60 (IC95 por ciento: 1,55 a 8,37, p = 0,003). CONCLUSIÓN: El presente estudio muestra que los niveles elevados de autoanticuerpos IgA para β2-gpI pueden estar independientemente asociados con la SM.

Clinical analysis of autoimmune hemolytic anemia in systemic lupus erythematosus / 中华风湿病学杂志

Objective To determine the clinical and serological characteristics of autoimmune hemolytic anemia (AIHA) in systemic lupus erythematosus (SLE) patients.Methods Seventeen patients were studied who had clinical features of AIHA among 222 hospitalized SLE patients in the Department of Rheumatology of Beijing Chaoyang Hospital were studied.Among the SLE patients without AIHA,34 patients were chosen by random sampling as controls.The patients' demographic data,clinical manifestations,laboratory test results and other examinations were analyzed retrospectively.Student's t test was used for the comparison of continuous variables,and chi-square test was used for the comparison of proportions.Results The prevalence of AIHA was 7.6％ in cohort of lupus patients.The positive rate of IgG anticardiolipin antibody in the AIHA group was significantly higher than that in the control group (71％ vs 15％,x2=15.366,P＜0.01 ).The occurrence of antiphospholipid antibody syndrome between the two groups had no statistical significant difference (x2=0.000,P=1.000).The frequencies of arthritis (12％,x2=4.554,P=0.033),malar rash (6％,x2=4.443,P=0.033),leukocytopenia (12％,x2=8.061,P=0.005) and lymphocytopenia (41％,x2=5.075,P=0.024) were lower in the AIHA group than those in the control group.Three patients in the AIHA group had alveolar hemorrhage in the course of SLE,while there was none in the control group (x2=3.586,P=0.058).Conclusion When lupus patients with AIHA are compared with those without AIHA,the positive rate of anticardiolipin antibody is higher,but the occurrence of antiphospholipid antibody syndrome does not increase in SLE patients with AIHA.And the frequencies of arthritis,malar rash,leukocytopenia and lymphocytopenia are lower in those patients with AIHA,however,patients with AIHA are prone to develop alveolar hemorrhage.

Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia

BACKGROUND/AIMS: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. METHODS: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. RESULTS: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/microL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. CONCLUSIONS: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.

Abordagem laboratorial das síndromes antifosfolípide e do aborto recorrente / Laboratories analyses indicated in antiphospholipid and recurrent abortion syndrome

Um aumento no potencial hemostático endometrial ocorre durante o ciclo menstrual, possibilitando, assim, a implantação embrionária, caso ocorra a fertilização. Defeitos nas proteínas de coagulação podem alterar esse estado de hipercoagulabilidade gestacional e desencadear perdas fetais por falhas na implantação ou na nutrição do embrião. A síndrome do aborto recorrente pode ser ocasionada por inúmeros fatores, entre eles anormalidades cromossômicas, anatômicas ou hormonais, ou ainda por defeitos nas proteínas de coagulação sanguínea ou plaquetária. Uma causa comum de abortos recorrentes é a síndrome antifosfolípide, uma desordem sistêmica, autoimune, caracterizada por trombose arterial e/ou venosa, morte fetal, abortos recorrentes e trombocitopenia, acompanhada de títulos elevados de anticorpos antifosfolípides: anticoagulante lúpico e/ou anticardiolipina. Pela íntima associação dessas síndromes, faz-se necessário investigá-las em pacientes que procuram os tratamentos de fertilização in vitro.

An increase in endometrial hemostatic potential occurs during the menstrual cycle, thus enabling the embryonic implantation in the occurrence of fertilization. Defects in the coagulation proteins may change this state of gestational hypercoagulability and cause fetal losses by failures in the implantation or nutrition of the embryo. The recurrent abortion syndrome can occur by many factors, including chromosomal, anatomical or hormonal abnormalities or defects in proteins of blood or platelet coagulation. A common cause of recurrent miscarriages is antiphospholipid syndrome, a systemic disorder, autoimmune, characterized by arterial and/or venous thrombosis, fetal death, recurrent miscarriages, and thrombocytopenia, accompanied by evidence of elevated antiphospholipid antibodies: lupus anticoagulant and/or anticardiolipin. Due to the intimate association of these syndromes, the investigation of them is necessary in patients seeking for in vitro fertilization treatment.

Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis / Prevalência de marcadores comuns de trombofilia e fatores de risco em pacientes indianos com trombose venosa primária

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56 percent) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9 percent each), followed by low protein S (16.6 percent). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

CONTEXTO E OBJETIVO: A trombose venosa ocorre como resultado da interação de fatores genéticos e adquiridos, incluindo resistência à proteína C ativada (APC-R), os níveis de fibrinogênio, antitrombina, proteína C, proteína S, anticoagulante lúpico e anticorpos anticardiolipina. Este estudo teve como objetivo verificar a prevalência de fatores trombofílicos frequentes em indianos com trombose venosa primária. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado em Mumbai. MÉTODOS: Foram testadas amostras de 78 pacientes com diagnóstico confirmado de trombose venosa e 50 controles. Foi realizada a dosagem sérica semiquantitativa (funcional) de proteína C, proteína S e antitrombina e a dosagem quantitativa de fibrinogênio (método de Clauss). Anticoagulantes lúpicos foram identificados por meio do tempo de tromboplastina parcial ativada sensível ao lúpus, e anticorpos anticardiolipina dependentes de β2-glycoproteína-I por ELISA. APC-R foi medida por método baseado em coagulação com plasma deficiente em fator V e veneno de Crotalus viridis. A análise estatística utilizou Epi-info (versão 6). RESULTADOS: A veia poplítea foi o local mais frequentemente afetado; 44 amostras (56 por cento) tiveram resultados anormais. Os achados mais frequentes foram elevação do fibrinogênio e APC-R (17,9 por cento cada), e baixa proteína S (16,6 por cento). CONCLUSÕES: Corroborando com a literatura, este estudo mostrou que a elevação do nível de fibrinogênio e a triagem para APC-R são importantes na avaliação de pacientes com trombose venosa, pois, individualmente ou em combinação, podem ter levado ao episódio trombótico primário. A frequência dos outros marcadores de trombofilia foi mais alta entre os doentes quando comparados aos controles, porém sem diferença estatisticamente significante.

Síndrome do anticorpo antifosfolípide causando oclusão bilateral de artérias e veias centrais da retina: relato de caso / Antiphospholipid syndrome and bilateral retinal artery and vein occlusion: case report

A síndrome do anticorpo antifosfolípide (SAF) tem sido associada a trombose de vasos arteriais e periféricos e de grande ou pequeno calibre. Também os vasos oculares estão sujeitos à ação destes auto-anticorpos que podem promover o aparecimento de perda visual transitória, diplopia, neuropatia óptica isquêmica e oclusão de artéria ou veia da retina. É descrito aqui, um caso de síndrome do anticorpo antifosfolípide com oclusão de vasos centrais arteriais e venosos da retina no intuito de chamar a atenção para este tipo de diagnóstico.

The antiphospholipid syndrome (APS) has been related to venous and arterial thrombosis of large and small vessels. Ocular vessels can also be involved causing transient visual loss, diplopia, ischemic optic neuropathy and central artery and venous occlusion. We describe here a case of antiphospholipid syndrome with occlusion of central retinal artery and vein to call the attention to this diagnosis.

Study on the feasibility of syphilis examination in the blood screening / 国际检验医学杂志

Objective To evaluate the best experimental technique with high-sensitivity and specificity for enhancing positive rate of syphilis screen test and preventing the blood dissemination of this disease.Methods Comparison of the results of TP-ELISA,TRUST and TPPA methods of syphilis examination was performed.Results Using three methods to exam 43,323 samples,299 samples were for positive syphilis.Among them, 294 positive samples with the ELISA method,the positive rate of syphilis test was 98.33%(294/299):92 positive samples with TRUST method,the positive rate only 30.77%(92/299);239 positive samples with TPPA method,the positive rate 79.93%(239/299).Conclusion TP-ELISA method with high sensitivity is suitable for the instrument standardization and data preservation,which is an ideal method for blood screen test of syphilis.For guarantee of blood safety and conventience and economic benefit of blood syphilis screen test, it is the best way to use both TP-ELISA and TRUST methods.The specificity of TPPA method is perfect, which is suitable for confirmation test of syphilis positive samples.

A Comparative Study of Anticardiolipin Antibodies in Syphilis and SLE / 中华皮肤科杂志

Objective To compare the intensity and isotype of anticardiolipin(ACL)antibodies in the sera from patients with syphilis and SLE.Methods IgG and IgM type of ACL antibodies were examined by ELISA in99syphilis patients and75SLE patients.Results Although similar positive percentage of IgG ACL antibodies was shown in syphilis and SLE patients,stronger absorbance(A value)was seen in syphilis patients(P

Study of the causes of fetal growth restriction with unclear etiologies / 中华妇产科杂志

Objective To investigate different factors related to fetal growth restriction (FGR) and to find out the possible causes of FGR with unclear etiologies. Methods Sixty-three women who were suspected of FGR during pregnancy between March 2002 and March 2003 were included in this study. Their age, body mass index (BMI) before pregnancy, and gestational weeks were recorded at the time when they were first diagnosed . Haemoglobin levels, haematocrit (HCT) ,TORCH, anticardiolipin antibody (ACA) , 50 gram glucose challenge test (50g GCT) , 75 gram oral glucose tolerance test (75g OGTT) , leptin levels, systolic/diastolic (S/D) ratio by color doppler monitor and chlamydia trachomatis (CT) were detected and urine culture was done in these groups during the same period. The gestational week, birth weight, body length and the gender were recorded at the delivery period. The FGR group was then divided into two subgroups according to the birth weights: study A group whose birth weights were lower than 10th% of the birth weights at the given gestational weeks (29 cases) and study B group whose birth weights were beyond 10th% (34 cases). The chromosome, leptin, C-peptide, insulin and TORCH of umbilical blood were measured at delivery. The other 25 normal pregnant women were included as control and the same tests were performed accordingly. Results The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test of study A were( 3. 8 ?0, 6) mmol/L and (4. 5 ?1. 1) mmol/L. The fetal lepin, C-peptide, and insulin were (7.3 ? 5. 2) ng/ml, (0. 5 ? 0. 3) nmol/L and (2. 3 ? 1. 3 ) mU/L The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of asymptomatic bacteriuria were 3.06, 20.7%, 24.1%, 44.8% and 62.1% respectively. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test of study B were (4. 4 ? 0. 7) mmol/L and (4. 6 ? 1. 1 ) mmol/L. The fetal lepin, C-peptide, and insulin were ( 13. 2 ? 11. 3 ) ng/ml, (0. 7 ? 0. 4) nmol/L and (4.3 ? 3.3) mU/L The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of asymptomatic bacteriuria were 2. 63, 2. 9% , 0% , 5.9% and 44. 1% respectively. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test in control were (4. 3 ? 0. 7) mmol/L and (5. 3 ? 1.2) mmol/L. The fetal lepin, C-peptide, and insulin were( 20. 5 ? 12. 0) ng/ml, (1. 0 ? 0. 4) nmol/L and ( 6. 3 ? 4. 0) mU/L The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of the asymptomatic bacteriuria were 2. 80, 0, 0, 0 and 24. 0% respectively. All these items were significantly higher in study A than those in the control (P

FⅤ Leiden mutation,the anticardiolipin antibodies and ischemic cerebrovascular disease in Chinese patients / 中华神经科杂志

Objective To study the prevalence of FⅤ Leiden mutation and its relationship to anticardiolipin antibodies (aCL) and ischemic cerebrovascular disease (ICVD). Methods The factor Ⅴ Leiden mutation was analyzed in 75 healthy and 118 ICVD patients using PCR-RFLP analysis.The anticardiolipin antibodies level was also measured by enzyme-linked immunosorbent assay along with international standards in 86 patients with ICVD.The resistance to activated protein C(APC-R )was measured in 27 patients. Results The mutation, in heterozygous form, was found in 6 cases out of 118 ICVD patients, with a prevalence of 5.1%.None of the 75 healthy were found to carry the FⅤ Leiden mutation.The patients who carried the FⅤ Leiden mutation were young, whose average age was 50 years old.In 27 patients whose APC-R was measured , 8 patients were positive.In 86 patients whose aCL level was also measured simultaneously, an elevated aCL level was found in 26 cases, of whom 3 cases were found carrying the FⅤ Leiden mutation as well, making the group of patient possess a prevalence of 11.5 %, showing no strongly statistical significance in contrast to the patients without elevated aCL 5.0%.However, within the total of 6 cases with FⅤ Leiden mutation found in this group, 3 cases were patients with elevated aCL.Conclusions It was suggested that although FⅤ Leiden mutation was accounted for a small proportion of patients with ICVD, it might play a crucial role in thrombosis. The prevalence of young patients who carried FⅤ Leiden mutation should be higher.The final combined analysis revealed FⅤ Leiden mutation which is of highly significant relation to aCL in this group of Chinese patients with ICVD.It's detection should be of greatly clinical significance in finding cause, predicting the progress, prevention and treatment.

Clinical significance of the anticardiolipin antibodies in patients with hemorrhagic fever with renal syn-drome / 中华传染病杂志

Objective To investigate the clinical significance of anticardiolipin antibodies (ACA)in patients with hemorrhagic fever with renal syndrome(HFRS).Methods The serum ACA- IgM and ACA-IgG in 175 cases of renal diseases and 50 healthy cases were detected by enzyme-linked immunosorbent assay(ELISA). The positive rates of ACA were calculated and compared among different groups.Results The positive rates of ACA-IgM and ACA-IgG in control group were both 0 (0/50),while they were 85.2%(46/54)and 24.1%(13/54)respectively in patients with HERS. 25.0%(13/52)and 21.2%(11/52)respectively in patients with lupus nephritis and 13.0%(9/69) and 8.7%(6/69)respectively in patients with nephrotic syndrome.The poshive rate of ACA lgM in patients with HFRS was higher than that in control group,lupus nephritis group and nephritic syn- drome group(P

Clinical characteristics of 115 Chinese patients with antiphospholipid syndrome and the analysis of different classification criteria / 中华风湿病学杂志

Objective To analyze three different classification criteria, the clinical characteristics of antiphospholipid syndrome(APS)in a cohort of Chinese patients. Methods From January 1996 to October 2006, APS patients diagnosed with different classification criteria were retrospectively studied. Results There were totally 120 APS patients fulfilled at least one criterion, One hundred and one patients fulfilled the 1988 Asherson criteria, 96 patients fulfilled the 1999 Sapporo criteria, and 115 patients fulfilled the 2006 Sydney criteria. The ratio of male to female in a cohort of 115 definite APS patients was 1 to 10.5. The mean period of the disease until entry into the study was 82.6 months, the mean age at study entry was(41?12)years. Ninety patients had thrombosis episodes, among which the most common presenting manifestations were deep venous thrombosis, stroke and skin vasculitis. Forty-six of 92 married women in our cohort had fetal morbidity. Catas- trophic APS occurred in 7 patients. The presence of anticardiolipin antibodies(aCL)was detected in 86 pa- tients, anti-beta-2 glycoproteinⅠantibodies in 58 patients and lupus anticoagulant(LA)in 27 patients. Conclusion The most common presenting manifestations are deep venous thrombosis, stroke and cutaneous manifestations. The sensitivity of Sydney classification criteria is improved by adding anti-beta-2 glycopreteinⅠantibody as one of the laboratory criteria. However, primary APS patients who only presented with thrombo- cytupenia and positive laboratory tests could not satisfy this criterion. In addition, the significance of autoanti- bodies to some coagulant factors in APS needs further study.