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1.
Rheumatology (Oxford) ; 63(3): 772-779, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37307082

RESUMO

OBJECTIVES: Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. METHODS: In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage. RESULTS: Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aß2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P < 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016). CONCLUSIONS: DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.


Assuntos
Síndrome Antifosfolipídica , Hiperlipidemias , Humanos , Síndrome Antifosfolipídica/complicações , Estudos Transversais , Sistema de Registros , Anticorpos Antifosfolipídeos
2.
Lupus ; 30(14): 2276-2285, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34915764

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.


Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , COVID-19 , Trombose , COVID-19/patologia , Humanos , Trombose/virologia
3.
Arthritis Care Res (Hoboken) ; 73(5): 717-721, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32583963

RESUMO

OBJECTIVE: To evaluate mean serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble Flt-1 (sFlt-1) in pregnant patients with systemic lupus erythematosus (SLE) with inactive disease, active lupus nephritis, and preeclampsia for differential diagnosis between these conditions. METHODS: Pregnant women with SLE, with singleton pregnancies and no other autoimmune diseases, were classified according to disease activity (inactive SLE and active lupus nephritis) and the presence of preeclampsia. Serum samples were collected within 3 weeks of delivery and frozen for subsequent blinded analysis through the enzyme-linked immunosorbent assay method. RESULTS: A total of 71 women were included, with 41 classified as having inactive SLE (group 1; Systemic Lupus Erythematosus Pregnancy Disease Activity Index [SLEPDAI] score <4), 15 with a diagnosis of active lupus nephritis (group 2, SLEPDAI score ≥4, including renal criteria), and 15 with a diagnosis of preeclampsia (group 3). Patients in group 3 had higher mean levels of sFlt-1 and lower mean levels of PlGF compared to groups 1 and 2, both findings with statistical significance. The sFlt-1:PlGF ratio was also significantly higher in patients with preeclampsia, while mean VEGF levels were higher in pregnant woman with active lupus nephritis compared to patients with preeclampsia or inactive SLE. CONCLUSION: Evaluation of serum VEGF, PlGF, and sFlt-1 levels can differentiate between preeclampsia, inactive SLE, and active lupus nephritis during pregnancy.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Pré-Eclâmpsia/diagnóstico , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Adulto Jovem
4.
Lupus ; 29(12): 1601-1615, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32883160

RESUMO

Obstetric antiphospholipid syndrome (APS) remains a clinical challenge for practitioners, with several controversial points that have not been answered so far. This Obstetric APS Task Force met on the 16th International Congress on Antiphospholipid Antibodies in Manchester, England, to discuss about treatment, diagnostic and clinical aspects of the disease. This report will address evidence-based medicine related to obstetric APS, including limitations on our current management, the relationship between antibodies against domain 1 of ß2GPI and obstetric morbidity, hydroxychloroquine use in patients with obstetric APS and factors associated with thrombosis after obstetric APS. Finally, future directions for better understanding this complex condition are also reported by the Task Force coordinators.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Comitês Consultivos , Animais , Anticorpos Antifosfolipídeos/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Congressos como Assunto , Feminino , Humanos , Gravidez , Complicações na Gravidez
5.
Rheumatology (Oxford) ; 57(suppl_5): v18-v25, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137591

RESUMO

This article describes three complicated cases in rheumatology and pregnancy. The first case elucidates the challenges in treating SLE in conjunction with pulmonary arterial hypertension, while the second case features an SLE-affected pregnancy with development of portal hypertension secondary to portal vein thrombosis related to APS. The third case is a pregnant woman with stable SLE who developed thrombotic microangiopathy caused by atypical haemolytic uraemic syndrome, and failed to improve despite multiple measures including biopsy and elective preterm delivery. There are grave and unique challenges for women with autoimmune disease, but adverse outcomes can sometimes be avoided with careful and multidisciplinary medical management. Pre-conception counselling with regard to medications and disease treatment should also include discussion of the advisability of pregnancy, which may be difficult for a patient, but present the best course for optimizing health outcomes.


Assuntos
Lúpus Eritematoso Sistêmico/terapia , Complicações Cardiovasculares na Gravidez/terapia , Complicações Hematológicas na Gravidez/terapia , Adulto , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/terapia , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/terapia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Lúpus Eritematoso Sistêmico/complicações , Veia Porta , Gravidez , Complicações Cardiovasculares na Gravidez/etiologia , Complicações Hematológicas na Gravidez/etiologia , Resultado da Gravidez , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Trombose Venosa/complicações , Trombose Venosa/terapia , Adulto Jovem
6.
Autoimmun Rev ; 15(10): 955-63, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27490204

RESUMO

The crucial issue for a better pregnancy outcome in women with autoimmune rheumatic diseases is appropriate planning, with counseling of the ideal timing and treatment adaptation. Drugs used to treat rheumatic diseases may interfere with fertility or increase the risk of miscarriages and congenital abnormalities. MTX use post-conception is clearly linked to abortions as well as major birth defects, so it should be stopped 3months before conception. Leflunomide causes abnormalities in animals even in low doses. Although in humans, it does not seem to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide, cholestyramine is given for washout. Sulfasalazine can be used safely and is an option for those patients who were on MTX or leflunomide. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancy centers because of the safety profile and its steroid-sparing property. Cyclosporine and tacrolimus can also be used as steroid-sparing agents, but experience is smaller. Although prednisone and prednisolone are inactivated in the placenta, we try to limit the dose to the minimal effective one, to prevent side effects. Antimalarials have been broadly studied and are safe during pregnancy and breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD), the anti-TNFs that have been used for longer are the ones with greater experience. The large monoclonal antibodies do not cross the placenta in the first trimester, and after conception, the decision to continue medication should be taken individually. The experience is larger in women with inflammatory bowel diseases, where anti-TNF is generally maintained at least until 30weeks to reduce fetal exposure. Live vaccines should not be administrated to the infant in the first 6months of life. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in pregnancy cannot currently be recommended.


Assuntos
Antirreumáticos/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Animais , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Lactação , Guias de Prática Clínica como Assunto , Gravidez , Resultado da Gravidez
7.
Autoimmun Rev ; 15(6): 493-500, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26827907

RESUMO

Even though the association of anti-phospholipid antibodies (aPL) with infertility is debated, infertile women are commonly screened for aPL. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing (i) the association between aPL and infertility, (ii) the positivity rate of criteria and non-criteria aPL in women with infertility, (iii) the association between aPL and assisted reproduction technologies (ART) outcome, (iv) the efficacy of medical treatments on ART outcome, and (v) the effects of ART on thrombotic risk. A total of 46 papers were considered; several limitations emerged: (i) wide heterogeneity in study populations, (ii) non-prospective design in 90% of studies, and (iii) aPL cutoffs not conforming to international guidelines in more than 75% of studies; aPL positivity not confirmed in 89% of studies. Most studies evinced an association between infertility and anti-ß2GPI antibodies and almost all non-criteria aPL. The association rate with infertility was below 50% for lupus anti-coagulant, anti-cardiolipin antibodies (aCL), and anti-phosphatidic acid antibodies. According to our estimates, overall positivity rates of criteria and non-criteria aPL tests are 6% and 3% among infertile women, 1% and 2% among controls, respectively. A significant difference in the positivity rate of patients versus controls emerged for aCL only. Five of 18 studies reported a detrimental effect of aPL on ART outcome. Only one of the six studies assessing the effects of treatment on ART outcome among aPL-positive infertile women reported a benefit. All relevant studies reported no increase in the rate of thrombosis among aPL-positive women undergoing ART.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Infertilidade Feminina , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/terapia , Estudos Prospectivos
8.
Front Immunol ; 6: 205, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25999948

RESUMO

Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it.

9.
Autoimmun Rev ; 13(8): 795-813, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24650941

RESUMO

Pregnancy morbidity is one of the clinical manifestations used for classification criteria of antiphospholipid syndrome (APS). During the 14th International Congress on Antiphospholipid Antibodies (aPL), a Task Force with internationally-known experts was created to carry out a critical appraisal of the literature available regarding the association of aPL with obstetric manifestations present in actual classification criteria (recurrent early miscarriage, fetal death, preeclampsia and placental insufficiency) and the quality of the evidence that treatment(s) provide benefit in terms of avoiding recurrent adverse obstetric outcomes. The association of infertility with aPL and the effectiveness of the treatment of patients with infertility and positive aPL was also investigated. This report presents current knowledge and limitations of published studies regarding pregnancy morbidity, infertility and aPL, identifying areas that need better investigative efforts and proposing how critical flaws could be avoided in future studies, as suggested by participants of the Task Force. Except for fetal death, there are limitations in the quality of the data supporting the association of aPL with obstetric complications included in the current APS classification criteria. Recommended treatments for all pregnancy morbidity associated to APS also lack well-designed studies to confirm its efficacy. APL does not seem to be associated with infertility and treatment does not improve the outcomes in infertile patients with aPL. In another section of the Task Force, Dr. Jane Salmon reviewed complement-mediated inflammation in reproductive failure in APS, considering new therapeutic targets to obstetric APS (Ob APS).


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Comitês Consultivos , Animais , Anticorpos Antifosfolipídeos/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Congressos como Assunto , Feminino , Humanos , Gravidez , Complicações na Gravidez
10.
Curr Rheumatol Rep ; 16(2): 403, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24390757

RESUMO

Women with persistently circulating antiphospholipid antibodies (aPL) have a higher incidence of recurrent abortions, fetal losses, pre-eclampsia, and placental insufficiency. Current treatment of patients with antiphospholipid syndrome (APS) during pregnancy with heparin and aspirin can act by preventing clot formation and improving live birth rates, but other obstetric morbidities remain high, especially in patients with a history of thrombotic events. In addition to the classical thrombotic placental events, other factors involving inflammation and complement activation seem to play a role in certain complications. In this article, we will review how medications interfere in the pathogenic mechanisms of APS, discuss the impact of current recommended treatment on pregnancy morbidity, and analyze new promising therapies.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Aborto Habitual/etiologia , Aborto Habitual/prevenção & controle , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Aspirina/uso terapêutico , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/prevenção & controle , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/prevenção & controle , Gravidez , Resultado da Gravidez , Resultado do Tratamento
11.
Isr Med Assoc J ; 14(12): 724-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23393708

RESUMO

BACKGROUND: Takayasu arteritis (TA) is a rare chronic granulomatous inflammatory disease of the aorta and/or its major branches and more frequently affects female patients before menopause. Since persistent inflammation may lead to arterial ischemia, hypertension is an important complication of TA. OBJECTIVES: To evaluate gestational results and complications in patients with TA. METHODS: We conducted a retrospective analysis of the medical records of patients with TA admitted to the high risk pregnancy clinic for women with systemic autoimmune diseases at Hospital Universitário Pedro Ernesto. RESULTS: From 1998 to 2011 we followed 11 pregnancies in 9 patients with TA; the patients' age ranged from 17 to 42 years and disease duration from 2 to 28 years. In 7 of the 11 pregnancies, uncontrolled blood pressure occurred before labor and preeclampsia was diagnosed in one. Two deliveries were preterm, one newborn was treated for sepsis, and four (36%) had intrauterine growth restriction (IUGR). CONCLUSIONS: Close monitoring improves the perinatal outcomes in patients with TA who are more prone to develop hypertension, preeclampsia and IUGR. Disease activity was not observed in our group of patients during pregnancy. Coordinated care between the obstetric, rheumatologic and cardiologic teams is the ideal setting to follow pregnant women with TA.


Assuntos
Pressão Sanguínea , Hipertensão/etiologia , Monitorização Fisiológica/métodos , Complicações Cardiovasculares na Gravidez/etiologia , Arterite de Takayasu/complicações , Adolescente , Adulto , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/fisiopatologia , Resultado da Gravidez , Prognóstico , Estudos Retrospectivos , Adulto Jovem
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