Primary antiphospholipid syndrome in a hemodialysis patient with recurrent thrombosis of arteriovenous fistulas / Síndrome antifosfolípide primária em paciente em hemodiálise com trombose recorrente de fístulas arteriovenosas

ABSTRACT Introduction: The antiphospholipid syndrome is a systemic autoimmune disease defined by recurrent vascular and/or obstetrical morbidity that occurs in patients with persistent antiphospholipid antibodies. Case presentation: A patient on hemodialysis with a primary antiphospholipid syndrome presented with recurrent vascular access thrombosis, obstetrical complications, and positive lupus anticoagulant. The patient had multiple arteriovenous fistulas that failed due to thrombosis. The obstetrical morbidity was defined by one miscarriage at the 7th week of gestation and a pregnancy complicated by pre-eclampsia with preterm delivery at the 28th week of gestation. A thorough thrombophilia screening confirmed the presence of antiphospholipid antibody. Lupus anticoagulant was present in plasma, measured on two occasions 12 weeks apart. Conclusion: Thrombophilias are inherited or acquired predispositions to vascular thrombosis and have been associated with thrombosis of the arteriovenous fistula. Patients on hemodialysis with recurrent vascular access thrombosis and presence of thrombophilia should be evaluated about the need for anticoagulant therapy with a vitamin K antagonist.

RESUMO Introdução: A síndrome antifosfolipídica é uma doença autoimune sistêmica definida por morbidade vascular e/ou obstétrica, recorrente, que acomete pacientes com anticorpos antifosfolípides persistentes. Apresentação do caso: Uma paciente em hemodiálise com síndrome antifosfolípide primária apresentou trombose recorrente do acesso vascular, complicações obstétricas e anticoagulante lúpico positivo. A paciente apresentava múltiplas fístulas arteriovenosas que falharam devido à trombose. A morbidade obstétrica foi definida por um aborto espontâneo na 7ª semana de gestação e uma gravidez complicada por pré-eclâmpsia com parto prematuro na 28ª semana de gestação. Um rastreamento completo de trombofilia confirmou a presença de anticorpo antifosfolípide. O anticoagulante lúpico estava presente no plasma, medido em duas ocasiões, com 12 semanas de intervalo. Conclusão: As trombofilias são predisposições hereditárias ou adquiridas para trombose vascular e têm sido associadas à trombose da fístula arteriovenosa. Pacientes em hemodiálise com trombose recorrente de acesso vascular e presença de trombofilia devem ser avaliados quanto à necessidade de terapia anticoagulante com um antagonista da vitamina K.

Síndrome antifosfolípido catastrófico "seronegativo" en pediatría: caso clínico / "Seronegative" catastrophic antiphospholipid syndrome in pediatrics: clinical case

INTRODUCCIÓN: El síndrome antifosfolípido es una trombofilia adquirida autoinmune, caracterizada por trombosis arteriales y/o venosas. En raras ocasiones este cuadro puede tener una presentación catastrófica, de elevada mortalidad, con presencia de microangiopatia y compromiso de tres o más órganos. OBJETIVO: Describir la presentación clínica y evolución de una paciente pediátrica con síndrome antifosfolípido catastrófico, con forma de inicio seronegativa, cuya respuesta a terapia agresiva fue favorable. CASO CLÍNICO: Paciente femenina adolescente, que debutó cuadro de una semana de evolución de dolor, incremento del volumen abdominal y edema en extremidades inferiores. Se diagnosticó lupus eritematoso generalizado y se descartó proceso neoplásico. Durante su evolución pre sentó diversos eventos trómboticos, al inicio con presencia de anticuerpos antifosfolípido negativos, que posteriormente fueron positivos. Cursó con deterioro multisistémico secundario a trombosis multiorgánica, requirió soporte hemodinámico y ventilatorio. Se manejó con heparina de bajo peso molecular, plasmaféresis, anticoagulación, inmunosupresión y bolos de rituximab con excelente respuesta. CONCLUSIONES: Consideramos este caso de interés por tratarse de un diagnóstico infrecuente en la edad pediátrica y cuya sospecha, manejo intensivo y oportuno, puede cambiar el pronóstico sombrío y de alta mortalidad de estos pacientes.

INTRODUCTION: The antiphospholipid syndrome is an acquired autoimmune thrombophilia, characterized by arterial and/or venous thrombosis. Rarely, this condition can have a catastrophic presenta tion, with high mortality, and presence of microangiopathy and involvement of three or more organs. OBJECTIVE: To describe the clinical presentation and evolution of a pediatric patient with catastrophic antiphospholipid syndrome, with a seronegative onset form, whose response to aggressive therapy was favorable. CLINICAL CASE: Adolescent female, with a one-week history of pain, increased abdo minal volume and edema in the lower extremities. Generalized lupus erythematosus was diagnosed and the neoplastic process was ruled out. During its evolution, she presented various thrombotic events, initially with the presence of negative antiphospholipid antibodies, which were subsequently positive. The patient presented multisystemic failure secondary to multiorgan thrombosis, required hemodynamic and ventilatory support. It was managed with low molecular weight heparin, plas mapheresis, anticoagulation, immunosuppression and boluses of rituximab with excellent response. CONCLUSIONS: We consider this case interesting because it is an infrequent diagnosis in the pediatric age and whose suspicion, timely and aggressive intensive management, can change the poor progno sis and high mortality of these patients.

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Takayasu arteritis and antiphospholipid antibody syndrome in an elderly woman

No abstract available.

Avaliação da agregação plaquetária em presença de anticorpos antifosfolípides: anti-β2GP1 e anticardiolipina / Evaluation of platelet aggregation in the presence of antiphospholipid antibodies: anti-β2GP1 and anticardiolipin

INTRODUÇÃO: A síndrome antifosfolípide (SAF) é uma condição autoimune que apresenta fenômenos trombóticos arteriais e venosos de repetição além de complicações obstétricas. Sua patogênese está associada à presença de anticorpos antifosfolípides e/ou anti-β2 glicoproteína I (β2GPI) que aparentemente modificam o efeito anticoagulante da β2GPI. A dimerização da β2GPI induzida por anticorpos parece estar relacionada à indução da agregação plaquetária contribuindo para o estado trombofílico na SAF. OBJETIVOS: O presente trabalho objetiva demonstrar a influencia dos anticorpos antifosfolípides em testes de agregação plaquetária com diferentes agonistas (ADP, colágeno e adrenalina). MÉTODOS: Foram analisados testes de agregação de plaquetas normais com diferentes agonistas (ADP, colágeno, adrenalina) na presença de soro contendo anticorpos antifosfolípides em diferentes concentrações. RESULTADOS: As análises obtidas mostraram uma inibição significativa (P < 0,05) nas curvas de agregação plaquetária induzidas por ADP e adrenalina quando comparadas ao controle. O paradoxo entre o estado protrombótico e a presença de autoanticorpos que in vitro apresentam atividade anticoagulante foi demonstrado na literatura, dificultando o entendimento patofisiológico da síndrome antifosfolípide. CONCLUSÃO: Os resultados obtidos demonstraram que o soro rico em anticorpos anticardiolipina e anti-β2GPI, ambas da classe IgG, interferem em testes de curvas de agregação plaquetária.

INTRODUCTION: The antiphospholipid syndrome (APS) is an autoimmune condition characterized by recurrent arterial and venous thrombosis, besides obstetric complications. The pathogenesis is associated with the presence of antiphospholipid and/or anti-b2-glicoprotein I (anti-b2GPI) antibodies that appear to change the anticoagulant activity of b2GPI. Antibody-induced dimerization of b2GPI seems to be related to the induction of platelet aggregation, contributing to the development of thrombosis in APS. OBJECTIVES: The objective of the present study is to demonstrate the influence of antiphospholipid antibodies in platelet aggregation tests with different agonists (ADP, collagen, and adrenaline). METHODS: We analyzed platelet aggregation tests with different agonists (ADP, collagen, adrenalin) when normal platelets were exposed to serum with different concentrations of antiphospholipid antibodies. RESULTS: Results demonstrated a significant inhibition in adrenalin- and ADP-induced platelet aggregation curves (P < 0.05) in all antibody concentrations tested when compared to the control. The paradox between the prothrombotic state and the presence of autoantibodies that show anticoagulant activity in vitro was demonstrated in the literature, making it difficult to understand the pathophysiologic mechanism of the antiphospholipid syndrome. CONCLUSION: Results showed that anticardiolipin and anti-b2GPI antibodies-rich serum, both of which belonging to the IgG class, can interfere with platelet aggregation curves.

Anticorpos antinucleossomo e síndrome antifosfolipídica: estudo observacional / Antinucleosome antibodies and primary antiphospholipid syndrome: an observational study

OBJETIVO: Avaliar a associação entre a presença de anticorpos antinucleossomo (anti-NCS) e a síndrome antifosfolipídica primária (SAFP) e o posterior desenvolvimento de lúpus eritematoso sistêmico (LES). MATERIAIS E MÉTODOS: Trinta e seis mulheres com o diagnóstico de SAFP foram avaliadas prospectivamente para manifestações de doenças reumáticas autoimunes e para a presença de anticorpos antifosfolípides, anticorpos antinucleares e anti-NCS/cromatina. RESULTADOS: Após um período médio de seguimento de 45,7 meses, anticorpos anti-NCS/cromatina foram detectados em apenas uma paciente (2,8%), que desenvolveu manifestações de LES tais como poliartrite, linfopenia, neurite óptica, lesões compatíveis com esclerose múltipla em substância branca cerebral e perfil de autoanticorpos altamente sugestivo de LES. CONCLUSÃO: A frequência de anticorpos anti-NCS/cromatina é baixa em pacientes com SAFP, e sua presença pode associar-se ao desenvolvimento de manifestações de LES.

OBJECTIVE: To study the association of anti-nucleosome (anti-NCS) antibodies in primary antiphospholipid syndrome (APS) and the development of systemic lupus erythematosus (SLE) during follow-up. MATERIALS AND METHODS: Thirty-six women with primary APS were evaluated prospectively for clinical features of systemic autoimmune diseases and for the presence of antiphospholipid antibodies, antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in only one patient (2.8%), who developed features of SLE including polyarthritis, lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin antibodies in primary APS patients is very low, and they may be associated with the development of SLE manifestations.

Efecto de los anticuerpos antifosfolipídicos en la formación y degradación de la malla de fibrina en pacientes con aborto recurrente / Effect of antiphospholipid antibodies on the formation and lysis of fibrin network in patients with recurrent miscarriage

En el presente trabajo se estudió el proceso de formación y disolución de la malla de fibrina y la generación de plasmina en un grupo de pacientes con aborto recurrente (AR) debido a la presencia de anticuerpos antifosfolipídicos (N= 10), mujeres con AR sin el síndrome antifosfolipídico (SAF) (N= 6) y se comparó con un grupo de mujeres sanas (N= 8). Del grupo de pacientes estudiadas con SAF, nueve fueron positivas para anticuerpos anticardiolipina (aCL), cinco para la anti-b2-glicoproteína I (anti-b2GPI), cuatro para ambos anticuerpos, una para anticuerpos antiprotrombina (aPT) y anticoagulante lúpico (AL). El proceso de formación de la fibrina y su disolución fue estudiado por turbidimetría y la generación de plasmina mediante sustrato cromogénico S2251. Las curvas de polimerización de la(s) paciente(s) con AR sin SAF y AL presentaron un incremento en la pendiente y turbidez final, comparado con las del grupo control de mujeres sanas. La velocidad de disolución del coágulo fue mayor en la paciente con AL (21 ± 0) 10-4 DDO/seg y en las AR sin SAF (19,6 ± 5,7) 10-4 DDO/seg, comparado con el grupo control (14,5 ± 2,8) 10-4 DDO/seg. La generación de plasmina estuvo incrementada solamente en las AR sin SAF (85 ± 24%) comparado con 52 ± 3% en el grupo control, p= 0,005. Los cambios observados en el proceso de polimerización y fibrinólisis de la(s) paciente(s) con AR sin SAF y AL pudieran estar relacionados con el incremento en los niveles de fibrinógeno, mientras que los de la generación de plasmina con la entidad mórbida.

The present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (RM), due to the presence of antiphospholipid antibodies (N= 10); as well as in women with RM without the antiphospholipid syndrome (APS) (N= 6), compared with those of a group of healthy women (N= 8). In the group of patients with APS, nine were positive for antibodies against cardiolipin (aCL), five for anti-b2-glycoprotein I (anti-b2GPI), four for both antibodies, and one for antibodies against prothrombin (aPT) and lupus anticoagulant (LA). Fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate S2251. The polymerization curves from RM patients without APS and the LA patient showed an increased slope and maximum turbidity compared to those of the control group. The speed of lysis was higher in the LA patient (21 ± 0) 10-4 DOD/seg and the RM patients without APS (19.6 ± 5.7) 10-4 DDO/seg, compared to that of the control group (14.5 ± 2.8) 10-4 DDO/seg. Plasmin generation increased only in RM patients without APS (85 ± 24%) against the control group (52 ± 3%), p= 0.005. The changes observed in the fibrin polymerization and lysis process of women with RM without APS and LA seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients´ morbidity.

Avaliação clínico-laboratorial de pacientes com síndrome antifosfolípide primária segundo a frequência de anticorpos antinucleares (FAN Hep-2) / Clinical and laboratory evaluation of patients with primary antiphospholipid syndrome according to the frequency of antinuclear antibodies (ANA Hep-2)

OBJETIVO: Avaliar a frequência de manifestações clínicas e laboratoriais em pacientes com síndrome antifosfolípide primária (SAFP) com anticorpos antinucleares positivos (FAN Hep-2+), comparados àqueles com esses anticorpos negativos (FAN Hep-2 -). PACIENTES E MÉTODOS: Estudo transversal em 58 pacientes (82,8 por cento mulheres) com SAFP. Foram avaliados os dados demográficos, clínicos, comorbidades, medicações e anticorpos antifosfolípides. RESULTADOS: Dos 58 pacientes incluídos no estudo, vinte (34,5 por cento) apresentaram presença de FAN Hep-2. Comparando-se o grupo de pacientes FAN Hep-2+ com aqueles FAN Hep-2 -, verificou-se que ambos os grupos de pacientes com SAFP não diferiram estatisticamente em relação aos dados demográficos, bem como em relação ao tempo de doença. Em relação às manifestações clínicas e laboratoriais, o grupo com FAN Hep-2 + apresentou maior frequência de trombose venosa profunda (85 versus 52,6 por cento, P = 0,04), uma frequência estatística e significativamente maior de anticardiolipina IgG (85 versus 52,6 por cento, P = 0,02) e uma tendência para anticardiolipina IgM (80 por cento versus 52,6 por cento, P = 0,05), bem como maiores medianas desses anticorpos [33 (0-128) versus 20 (0-120) GPL, P = 0,008] e [33 (0-120) versus 18,5 (0-120) MPL, P = 0,009]. Tal diferença não foi observada no que se refere a outras manifestações da SAF, presença de comorbidades, estilo de vida e uso de medicações. CONCLUSÃO: Pacientes com SAFP que apresentam FAN Hep-2+ têm maior frequência de trombose venosa profunda e anticardiolipinas IgG e IgM.

OBJECTIVE: To evaluate the frequency of clinical and laboratory manifestations in patients with primary antiphospholipid syndrome (PAPS) with positive antinuclear antibodies (ANA Hep-2+) compared to those in whom this antibody is negative (ANA Hep-2-). PATIENTS AND METHODS: This is a transversal study with 58 patients (82.8 percent females) with PAPS. Demographic and clinical data, comorbidities, medications, and antiphospholipid antibodies were evaluated. RESULTS: Twenty (34.5 percent) out of 58 patients were positive for ANA Hep-2. Comparing the group of patients ANA Hep-2+ with those that were ANA Hep-2-, it was observed that both groups of patients with APS did not show statistically significant differences regarding demographic data, as well as the duration of the disease. As for clinical and laboratorial manifestations, the ANA Hep-2+ group showed higher frequency of deep venous thrombosis (85 versus 52.6 percent, P = 0.04), a statistically higher frequency of anticardiolipin IgG (85 versus 52.6 percent, P = 0.02), and a tendency for anticardiolipin IgM (80 percent versus 52.6 percent, P = 0.05), as well as greater medians of those antibodies [33 (0-128) versus 20 (0-120) GPL, P = 0.008] and [33 (0-120) versus 18,5 (0-120) MPL, P = 0.009]. Such difference was not observed regarding other manifestations of APS, presence of comorbidities, lifestyle, and medications used. CONCLUSIONS: Patients with PAPS with ANA Hep-2+ have a higher frequency of deep venous thrombosis and anticardiolipin IgG and IgM.

Polimorfismo Val247Leu do gene β2-glicoproteína 1 pode justificar a gênese de anticorpos antiβ2GP1 e síndrome do anticorpo antifosfolípide na hanseníase multibacilar / Val247Leu polymorphism of β2 glycoprotein 1 gene may justify the genesis of anti β2GP1 antibodies and Antiphospholipid Syndrome in Multibacillary Leprosy

FUNDAMENTOS - Anticorpos antifosfolípides (AAF), como antiβ2GP1 (β2-glicoproteína 1), são descritos na hanseníase multibacilar (MB) sem, contudo, caracterizar a síndrome do anticorpo antifosfolípide (SAF), constituída por fenômenos tromboembólicos (FTE). A mutação Val247Leu no V domínio da β2GP1 - substituição da leucina por valina - expõe epítopos crípticos com consequente formação de anticorpos antiβ2GP1. OBJETIVO: Avaliar a associação do polimorfismo Val247Leu do gene β2GP1 com títulos de anticorpos antiβ2GP1 na hanseníase. MÉTODO: O polimorfismo Val247Leu foi detectado por PCR-RFLP, e os títulos de anticorpos antiβ2GP1, por Elisa. RESULTADOS: O genótipo Val/Val estatisticamente predominou no grupo de hansênicos, em relação ao controle. Embora maiores títulos de anticorpos antiβ2GP1 IgM estivessem alocados no grupo MB com genótipos Val/Val e Val/Leu, não houve diferença estatística em relação ao genótipo Leu/Leu. Dos sete pacientes MB com FTE, quatro apresentaram heterozigose, e três Val/Val homozigose. CONCLUSÃO: A prevalência do genótipo Val/Val no grupo de hansênicos pode justificar parcialmente a presença de anticorpos antiβ2GP1 na forma MB. A heterozigose ou homozigose Val/Val nos sete pacientes com hanseníase MB e FTE corroboram a implicação de expressão fenotípica anômala da β2GPl e formação de anticorpos antiβ2GPl, com consequente FTE e SAF.

BACKGROUND - Multibacillary (MB) leprosy may be manifested with antiphospholipid antibodies (aPL), among which anti-β2GP1 (β2-glycoprotein 1). High titers of aPL are associated with APS (Antiphospholipid Syndrome), characterized by thrombosis. The mutation Val247Leu in the domain V of β2GP1 exposes hidden epitopes with consequent development of anti-β2GP1 antibodies. OBJECTIVE: To evaluate the Val247Leu polymorphism of β2GP1 gene and its correlation with anti-β2GP1 antibodies in leprosy patients. METHODS: The Val247Leu polymorphism was performed by PCR-RFLP and anti-β2GP1 antibodies were measured by ELISA. RESULTS: The genotypic Val/Val was more prevalent in the leprosy group, compared to controls. Regarding the 7 MB patients with APS, four presented heterozygosis and three, Val/Val homozygosis. Although higher titrations of anti-β2GP1 IgM antibodies were seen in MB leprosy group with Val/Leu and Val/Val genotypes, there was no statistical difference when compared to Leu/Leu genotype. CONCLUSION: The prevalence of Val/Val homozygosis in leprosy group can partially justify the presence of anti-β2GP1 IgM antibodies in MB leprosy. The description of heterozygosis and Val/Val homozygosis in 7 patients with MB leprosy and thrombosis corroborates the implication of anomalous phenotype expression of β2GP1 and development of anti-β2GP1 antibodies, with consequent thrombosis and APS.

Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-β2-glycoprotein-I antibodies / Resistencia a la proteína C activada y actividad de anticoagulante lúpico inducidas por plasma y por anticuerpos purificados humanos del IgG anti β2-glicoproteína I

ABSTRACT Introduction. We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-β2-glycoprotein-I (anti-β2GP-I) antibodies. Patients and methods. We studied plasma and sera samples from 29 patients with persistently positive anti-β2GP-I: 22 with thrombosis (12 with primary APS, 10 with APS secondary to SLE) and seven without thrombosis (all with SLE); 25 healthy subjects were studied as controls. We detected anticardiolipin antibodies (ACA); IgG (and its subclasses) and IgM anti-β2GP-I, on irradiated and non-irradiated plates by ELISA. APCR was assessed by the activated partial thromboplastin time (APTT)-based assay and by the modified test. The FV Leiden mutation was studied by PCR. LA determination included screening and confirmatory dRVVT. Serum anti-β2GP-I were affinity purified on sepharose columns and their isotype, subclass, and reactivity against various antigens were studied by ELISA. Results. We found that titers of IgG anti-β2GP-I on irradiated plates were higher than on non-irradiated plates (p = 0.002), IgG2 was the predominant subclass. Fifteen patients (13 with thrombosis) had LA and 15 (also 13 with thrombosis) induced the APCR phenotype. Eleven (all with thrombosis) had both. Two patients were heterozygous for the Leiden mutation. Two purified antibodies, monospecific for β2GP-I, induced an in vitro APCR phenotype and LA activity. Conclusions. Our results seem to indicate that the inhibition of the APC anticoagulant function by IgG2 anti-β2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS.

Introducción. Investigamos la resistencia a la proteína C activada (RPCA) y la actividad de anticoagulante lápico (AL), inducidas por anticuerpos anti-β2-glicoproteína-I (anti-β2GP-I). Pacientes y métodos. Estudiamos los plasmas y sueros persistentemente positivos para anti-β2GP-I de 29 pacientes: 22 tuvieron trombosis (12 con síndrome de antifosfolípidos (SAF) primario y 10 con SAF secundario a lupus erítematoso generalizado (LEG)) y siete sin trombosis (todos con LEG). Como controles estudiamos 25 sueros de personas clínicamente sanas. Detectamos anticuerpos anticardiolipina, anti-β2GP-I IgG (y sus subclases) e IgM por ELISA en placas irradiadas y no irradiadas. Evaluamos la RPCA por medio del tiempo parcial de tromboplastina activada y por la prueba modificada. Estudiamos la mutación FV de Leiden por PCR y el anticoagulante lápico con el método de dRVVT screening y confirmatorio. Después de purificar los anti-β2GP-I séricos con una columna de antígeno unido a sefarosa, analizamos por ELISA sus isotipos, subclases y reactividad contra β2GP-I y algunos fosfolípidos. Resultados. Los títulos de anti-β2GP-I IgG fueron más altos en placas irradiadas que en no irradiadas (p = 0.002), predominó la subclase IgG2. Quince plasmas (13 de pacientes con trombosis) tuvieron AL y 15 (13 también de pacientes con trombosis) indujeron el fenotipo de RPCA. Once plasmas (todos de pacientes con trombosis) indujeron ambas actividades. Dos pacientes fueron heterocigotos para la mutación de Leiden. Dos anticuerpos purificados monoespecíficos para β2GP-I indujeron el fenotipo de la RPCA y la actividad de AL in vitro. Conclusiones. Nuestros resultados sugieren que la RPCA, inducida por los anti-β2GP-I que concomitantemente tienen actividad de AL, puede tener implicaciones patogénicas en la trombofílía del SAF.

Cut-off levels based on deviation from standard negative control is better than moderate level based on fixed cut-off for ACA assessed using ELISA for the diagnosis of antiphospholipid syndrome.

AIM: To assess the consistency of the standard negative control of IgG and IgM ACA levels within runs and batches of tests, and levels of ACA agreement between those established according to deviation from standard negative control and those established based on a fixed level cut off. METHODS: Serum samples of 148 patients who presented an INR < 0.9 or prothrombin activity of > 130% or aPTT below 0.8 times control or thrombosis with aPTT below 1.2 times control were tested in a 22-time running test to determine IgG and IgM ACA levels using Quanta Lite ACA IgG (HRP) and Quanta Lite ACA IgM (HRP) commercial reagents. RESULTS: Coefficients of variant within runs and batches of standard negative control IgG and IgM ACA levels were 19.30% and 29.17% respectively. Using kappa statistics to determine degree of agreement between cut-off levels by deviation from standard negative control and fixed cut-off level of ACA identified using ELISA, the disagreement in IgM and IgG were k 0.30, and 95% CI of k 0.27 to 0.34 (z = 1.033, p = 0.3015), and k 0.63, and 95% CI of k 0.53 to 0.73 (z = 1.411, p = 0.1584) for cut-off levels based on deviations from standard negative control and fixed cut-off levels respectively. Cut-off levels based on deviation from standard negative control was more sensitive, with a 92% predictive true positive value, compared to a 69% predictive true positive value by fixed cut-off levels of IgM ACA detected using ELISA, and nearly equivalent to IgG ACA, with 84.4% and 87.1% predictive true positive values respectively. CONCLUSION: Cut-off points based on fixed levels of ACA detected using ELISA cannot be applied, because both IgG and IgM ACA levels of standard negative control were inconsistent among runs and batches. Cut-off points based on the deviation of 3 standard negative control levels for IgG ACA and based on deviations of 2.5 times from standard negative control levels for IgM ACA were better than cut off by fixed levels of ACA in producing true positive results.

Hiperhomocisteinemia como factor de riesgo trombótico en pacientes con Lupus Erimatoso Sistémico y Síndrome Antifosfolipido / Hyperhomocystinemia as a thrombotic risk factor in patients suffering from systemic lupus erithematosus and antiphospholipid syndrome

Objetivos: Determinar la prevalencia de hiperhomocisteinemia (hiperhcy) en pacientes con lupus eritematoso sistémico (LES) con y sin síndrome antifosfolípido (SAF); comparar los niveles de homocisteína (Hcy) entre pacientes con LES (con y sin SAF asociado) y un grupo de controles sanos y determinar la correlación entre hiperhcy y la presencia de anticuerpos antifosfolípidos. Pacientes y métodos: Se estudiaron 44 ptes con LES, portadores o no de SAF. Se los dividió en 2 grupos: 17 con LES y SAF y 27 con LES sin SAF y se compararon con 24 controles sanos. A todos se les realizó interrogatorio, examen físico y pruebas de laboratorio: anticuerpos anticardiolipinas (aCL), anticoagulante lúpico y Hcy. Se consideró hiperhcy a valores superiores a 9. A los ptes con hiperhcy se los trató con ácido fólico + B6 + B 12 durante un mes. Análisis estadístico: variables cualitativas: Chi cuadrado o Exacta de Fischer y cuantitativas: test T de Student o MannWhitney test. Resultados y conclusiones: Hubo 35 manifestaciones trombóticas en los 44 pacientes. Se encontró Hiperhcy en 27 ptes con LES (61,4%), de los cuales 12 tenían SAF. La diferencia entre los valores de Hcy de los pacientes con o sin SAF no fue significativa (p=0,42). Comparando las concentraciones de Hcy entre pacientes y controles, la diferencia fue muy significativa (p=0,002).También tuvo significación estadística la diferencia entre las concentraciones de Hcy de los pacientes con LES sin SAF vs. controles (p=0,015) y LES con SAF vs. controles (p=0,003). A 33 ptes se les dosó aCL: 20 (60,6%) fueron (+). De estos, 15 (75%) tenían hiperhcy. De los 27 pacientes con LES que tenían hiperhcy, sólo 18 cumplieron con el mes de tratamiento con a.fólico+B6+B12. 16 de 18 (88,8%) normalizaron o disminuyeron la Hcy.

Objectives: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrome; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. Patients and methods: we studied 44 SLE patients: 17 had antiphospholipid syndrome and 27 didn't have it, and we compared tbem to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitBI2 a month along. Statistical analysis: qualitative variables: chi square or Fischer's; quantitative variables: Student's T test or Mann-Whitney's test. Results and conclusions: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrome. Hcy concentrations patients vs. controls was statisticaly different (p=0,002). There was also statistically different the hcy concentration from SLE patients with SAF vs controls (p=0,003) and without SAF vs controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL( +). 15(75%) of them had hiperhcy.

Hiperhomocisteinemia como factor de riesgo trombótico en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido / Hyperhomocysteine like thrombocytic risk factor in patient with systemic lupus erythematous with antiphospholipid syndrome

Objetivos: Determinar la prevalencia de hiperhomocisteinemia (hiperhcy) en pacientes con lupus eritematoso sistémico (LES) con y sin síndrome antifosfolípido (SAF); comparar los niveles de homocisteína (Hcy) entre pacientes con LES (con y sin SAF asociado) y un grupo de controles sanos y determinar la correlación entre hiperhcy y la presencia de anticuerpos antifosfolípidos. Pacientes y métodos: Se estudiaron 44 ptes con LES, portadores o no de SAF. Se los dividió en 2 grupos: 17 con LES y SAF y 27 con LES sin SAF y se compararon con 24 controles sanos. A todos se les realizó interrogatorio, examen físico y pruebas de laboratorio: anticuerpo s anticardiolipinas (aCL), anticoagulante lúpico y Hcy. Se consideró hiperhcy a valores superiores a 9. A los ptes con hiperhcy se los trató con ácido fólico + B6 + B 12 durante un mes. Análisis estadístico: variables cualitativas: Chi cuadrado o Exacta de Fischer y cuantitativas: test T de Student o MannWhitney test. Resultados y conclusiones: Hubo 35 manifestaciones trombóticas en los 44 pacientes. Se encontró Hiperhcy en 27 ptes con LES (61.4%), de los cuales 12 tenían SAF. La diferencia entre los valores de Hcy de los pacientes con o sin SAF no fue significativa (p=0,42). Comparando las concentraciones de Hcy entre pacientes y controles, la diferencia fue muy significativa (p=O,002).También tuvo significación estadística la diferencia entre las concentraciones de Hcy de los pacientes con LES sin SAF vs. controles (p=0,015) y LES con SAF vs. controles (p=0,003). A 33 ptes se les dosó aCL: 20 (60,6%) fueron (+). De estos, 15 (75%) tenían hiperhcy. De los 27 pacientes con LES que tenían hiperhcy, sólo 18 cumplieron con el mes de tratamiento con a.fólico+ B6+ B 12. 16 de 18 (88,8%) normalizaron o disminuyeron la Hcy.

Objectives: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrome; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. Patients and methods: we studied 44 SLE patients: 17 had antiphospholipid syndrome and 27 didn't have it, and we compared them to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitBI2 a month along. Statistical analysis: qualitative variables: chi square or Fischer's; quantitative variables: Student's T test or Mann Whitney’s test. Results and conc1utions: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrome. Hcy concentrations patients vs. controls was statistically different (p=0,002). There was also statistically different the hcy concentration from SLE patients with SAF vs controls (p=O,003) and without SAF vs. controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL( +). 15(75%) of them had hiperhcy.

Laboratory identification of lupus anticoagulants using the combination of activated partial thromboplastin time and Russell's viper venom at two phospholipid concentrations.

The most appropriate combination of tests for lupus anticoagulants (LA) is unknown. The standard double centrifugation method to prepare plasma was inadequate for platelet elimination, interfering with kaolin clotting time and mixing studies. In the present study, the percentage correction of activated partial thromboplastin time (APTT) and Russell's viper venom time (RVVT) by high compared with low concentrations of phospholipid was used for both screening and confirmation of LA. Abnormality in either one was reported as positive. The specificity of the tests in 122 individuals without LA was 100 per cent for RVVT and 96.7 per cent for APTT, which yielded false positive by heparin. The mixing study was omitted from the authors' strategy without decreasing the specificity. In 795 patients with thrombosis, LA was detectable in 6.03 per cent. The sensitivity of diluted activated partial thromboplastin time (dAPTT) and diluted Russell's viper venom time (dRVVT) alone, compared with the combination of the two was 83.3 per cent and 79.2 per cent respectively. Therefore, this new test scheme is a simple, inexpensive and efficient method for Thai patients.

Agrupacion diagnostica del sindrome antifosfolipidico con base en los niveles sericos de IgG anticardiolipina / Classificatory limits to diagnosis antiphospholipid syndrome (SAF)

Objetivo: proponer, mediante métodos matemáticos de agrupamiento, límites para la clasificación diagnóstica del síndrome antifosfolipídico (SAF), en pacientes con trombosis venosa o arterial, en relación con los niveles séricos de anticuerpos IgG anticardiolipina (anti-cLP), única variable continua capaz de discriminar el diagnóstico de SAF. Tipo de estudio: estudio descriptivo prospectivo. Lugar y tiempo de estudio: Unidades de Hematología y Reumatología de la Facultad de Medicina de la Universidad Nacional de Colombia con sede en el Hospital San Juan de Dios de Bogotá, entre el 5 de enero de 1998 y el 12 de julio de 2000. Material y métodos: se incluyeron todos los pacientes con edad igual o mayor a 17 años, con eventos incidentes que cumplieran con la definición operacional de evento oclusivo vascular, arterial o venoso. Fueron evaluados en total 42 pacientes, a quienes se les documentó edad, sexo, diagnóstico de lupus eritematoso sistémico y se les cuantificó en unidades GPL, mediante técnica de micro ELISA, los niveles séricos de anticuerpos IgG anti-cLP. Se realizó un análisis de conglomerados, combinando un análisis jerárquico aglomerante inicial con un análisis ulterior no jerárquico (de "K-medias"). La matriz de proximidad del análisis jerárquico aglomerante empleó el cálculo de distancias euclidianas para todos los pares de casos, con base en una única variable estandarizada ( IgG anti- cLP). La regla de agrupamiento utilizada fue el promedio entre grupos. Se emplearon la media, la mediana y los valores mínimos y máximos de la variable analizada, para describir las medidas de resumen que determinaron las diferencias entre los grupos. Resultados: la relación mujer: hombre del total de 42 pacientes incluidos, fue 3.7: 1. La interpretación del dendograma elaborado a partir de la matriz de los diferentes coeficientes de aglomeración, indicó que podrían ser tres los conglomerados a formar. Los valores mínimos y máximos de unidades GPL de IgG anti-cLP para cada uno de los tres conglomerados formados fueron: Grupo 1, 7.5 y 49.8; Grupo 2, 61.7 y 109; Grupo 3,174 y 190. Discusión: se propone el diagnóstico de SAF inequívoco en pacientes con trombosis vascular con niveles séricos de anticuerpos IgG anti-cLP iguales o superiores a 50 unidades GPL y considerar otros diagnósticos para títulos inferiores, o bien, complementar el estudio con pruebas para la detección de...

Anticardiolipin antibodies in women with recurrent abortion

The present study sought to determine whether the level of anticardiolipin antibodies in women with recurrent abortion differed from that in the general population. Enzyme-linked immunosorbent assay was used for detection of anticardiolipin antibodies in a group of 26 patients defined as habitual aborters [at least three consecutive spontaneous abortions], and in a control group of 26 patients each of whom had had at least one live birth without pregnancy wastage. A high level of anticardiolipin antibody activity was detected among 19.23% of the habitual aborters but in none of the controls, indicating an association between anticardiolipin antibody level and habitual abortion

Primary antiphospholipid syndrome in stroke in the young.

Antiphospholipid syndrome is an uncommon cause of stroke. A 12 year old girl with this syndrome is reported who presented with thrombotic stroke and high titres of anticardiolipin (aCL) and lupus anticoagulant (LAC). The patient improved subsequently and was put on aspirin. The present report highlights the importance of screening for aCL and LAC in cases of stroke in young patients.

Prevalência de anticorpos anticardiolipina em doadores voluntários de banco de sangue / Anticardiolipin antibodies in blood donors of Sâo José do Rio Preto blood center

A presença de anticorpos anticardiolipina ou anticoagulante lúpico em pacientes com trombose arterial ou venosa, aborto de repetiçäo ou trombocitopenia estabelece o diagnóstico da síndrome dos anticorpos antifosfolipídios. O presente estudo teve como objetivo avaliar a prevalência dos anticorpos anticardiolipina em doadores voluntários de banco de sangue. Foram avaliados 100 doadores voluntários de banco de sangue, sendo 83 (83 por cento) do sexo masculino e 17 (17 por cento) do sexo feminino, com idade entre 21 e 59 anos (média de 35,4 anos). Os anticorpos anticardiolipina foram dosados pela técnica de enzima imuno ensaio e por diluiçäo, cujos valores 1/50 e 1/100 ou menos diluídos foram considerados fracamente reagentes (ou de baixo título), e os mais diluídos (acima de 1/100) foram considerados positivos (ou de alto título). Encontraram-se baixos títulos para os anticorpos anticardiolipinas em 6 (6 por cento) pacientes e alto título em 1 (1 por cento). A prevalência dos anticorpos anticardiolipinas mostrou-se semelhante ao da literatura.