Effect of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19.

OBJECTIVE: To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in Sao Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-ß2-Glycoprotein-I (aß2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. RESULTS: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m2), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. CONCLUSION: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Investigation of the relationship between thrombophilic disorders and brain white matter lesions in migraine with aura.

BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.

ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.

The meaning of non-criteria clinical manifestations in a real-life primary antiphospholipid syndrome cohort.

OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.

miR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome.

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-ß2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.

Cognitive dysfunction and serum levels of brain-derived neurotrophic factor (BDNF) in primary anti-phospholipid syndrome (PAPS).

OBJECTIVES: Cognitive dysfunction (CD) is a poorly understood non-stroke central neurological manifestation in anti-phospholipid syndrome (APS). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in neural plasticity and could potentially be a biomarker of CD in primary APS (PAPS). The aim of the study is to assess CD in PAPS patients and to evaluate its association with clinical data, anti-phospholipid antibodies and serum BDNF levels. METHODS: This cross-sectional study compared 44 PAPS patients and 20 healthy controls matched for age, gender and education. PAPS patients and controls underwent a standardized cognitive examination. The demographic, clinical and laboratory characteristics of patients were recorded. Serum BDNF was measured by Enzyme Linked Immunosorbent. RESULTS: Fourteen (31.8%) of the 44 patients with PAPS had CD compared with only one (5%) healthy control (P =0.019). PAPS patients presented lower serum BDNF levels when compared with controls (P =0.007). Lower levels of BDNF were associated with CD in PAPS patients (P =0.032). In the univariate analysis, a positive association was found between CD and livedo reticularis, deep vein thrombosis, stroke, seizure, smoking as well as a negative association with Mini Mental State Examination and serum BDNF. According to multivariate analysis, the only independent predictor of CD in PAPS was stroke (OR 137.06; 95% CI: 4.73, 3974.32; P =0.004). CONCLUSIONS: CD is commonly reported in PAPS patients; however, its assessment lacks in standards and objective screening tests. The association between CD and low serum BDNF suggests that this neurotrophin can be a promising biomarker for PAPS cognitive impairment.

Risk factors for early severe preeclampsia in obstetric antiphospholipid syndrome with conventional treatment. The impact of hydroxychloroquine.

OBJECTIVE: The first aim was to retrospectively identify risk factors for the development of early severe preeclampsia (sPE) in patients with obstetric antiphospholipid syndrome (OAPS) who received conventional treatment (CT). The second aim was to evaluate the impact of hydroxychloroquine (HCQ) in preventing early sPE among a subgroup of patients considered at high risk. METHODS: A total of 102 women diagnosed with OAPS and treated with CT since the diagnosis of pregnancy were selected. At the end of pregnancy, we identified risk factors associated with early sPE. According to these risk factors, we collected a new cohort of 42 patients who presented high-risk factors for developing early sPE and split them into two groups according to the treatment received: group A, CT (30 patients); and group B, CT+HCQ (12 patients). We evaluated and compared pregnancy outcomes in both groups. RESULTS: According to the multivariate analysis, risk factors associated with early sPE and CT were triple positivity for antiphospholipid antibodies (aPL) (OR = 24.70, [4.27-142.92], p < 0.001) and a history of early sPE (OR = 7.11, [1.13-44.64], p = 0.036). A low-risk aPL profile was associated with a good response to CT in preventing early sPE (OR = 0.073, [0.014-0.382], p = 0.002). High-risk patients treated with CT+HCQ had a significantly lower early sPE rate than those treated with CT only (8.3% vs 40.0%; p = 0.03). CONCLUSION: Triple positivity for aPL and a history of early sPE are potential strong risk factors for the development of early sPE. HCQ might be an interesting therapeutic option for patients with high-risk factors for early sPE.

Primary antiphospholipid syndrome, Addison disease, and adrenal incidentaloma.

Primary adrenal failure comprises an insufficient production of mineralocorticoids and glucocorticoids in the adrenal cortex. A rare manifestation of antiphospholipid syndrome (APS) is adrenal failure. The majority of patients with adrenal involvement in APS develop an irreversible cortisol deficiency and atrophy of the adrenal glands. Adrenal incidentalomas are adrenal masses larger than 1 cm that are discovered in the course of diagnostic evaluation or treatment for another medical condition. Its prevalence is calculated in 1.5-9% of individuals. We describe an exceptional case of a 23-year-old male patient with APS with persistent high levels of antiphospholipid antibodies (aPL) from the time of diagnosis, who developed Addison's disease as a manifestation of APS with atrophy of the adrenal glands, in whom an adrenal incidentaloma was developed later and was corroborated as an aldosterone-producing adenoma. Currently, the patient is asymptomatic and without manifestations of tumor recurrence. The protumoral effect of elevated and persistent aPL is discussed.

Anorectal diseases in patients with Antiphospholipid syndrome: a cross-sectional study

Abstract Background: Hemorrhoid disease (HD) is one of the most common gastrointestinal complaints worldwide, affecting 4.4% of the general population in the United States. Since antiphospholipid syndrome (APS) may lead to intra-abdominal thrombosis, one may expect that this condition can impact the risk for HD development. Additionally, as APS patients are more prone to thrombosis and treatment with anticoagulants may increase risk of bleeding, one may also infer that rates of HD complications may be higher in this scenario. Nevertheless, no data in these regards have been published until now. The objective of the present study is to evaluate frequency of HD and describe its complications rates in antiphospholipid syndrome APS patients. Methods: We consecutively invited patients who fulfilled APS criteria to undergo proctological examination. After examination, patients were divided in two groups, based on the presence of HD, and compared regarding different clinical manifestations and antiphospholipid profile. We performed the analysis of the data, using chi-square and Mann Whitney U when applicable and considering a significance level of 0.05. Multivariate regression analysis included age and variables with p < 0.10 in the bivariate analysis. Results: Forty-one APS patients agreed to undergo proctological examination. All were female and overall median age was 43 (36-49). Seventeen (41.4%) patients were diagnosed with HD, with the following frequency distribution: 7 internal (41.2%), 4 external (23.5%) and 5 mixed hemorrhoids (29.4%). Of the internal hemorrhoids, 5 patients were classified as grade I (71.4%), 1 grade II (14.3%), and 1 grade IV (14.3%). Prior gestation ( p = 0.067) and constipation ( p = 0.067) correlated with a higher frequency of HD. In multivariate analysis, constipation remained as an important risk factor (OR 3.92,CI95% 1.03-14.2, p = 0.037). Five out of 17 patients (29.4%) reported anal bleeding, but it did not correlate with warfarin dose ( p = 0.949). Surgical treatment was indicated for 10 patients (58.8%). Other anorectal findings were anal fissure, plicoma, condyloma and one chlamydial retitis. Conclusion: We found an unexpected high frequency of hemorrhoids in APS patients, with a great proportion requiring surgical treatment.(AU)

Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy.

INTRODUCTION: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. OBJECTIVES: To determine whether epidemiological, clinical and immunological factors played a role in the long-term persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. METHODS: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. RESULTS: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-ß2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. CONCLUSION: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Antiphospholipid Antibody Syndrome and Infertility.

Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies (aPLs), thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. The objective of the present study was to review the pathophysiology of APS and its association with female infertility. A bibliographic review of articles of the past 20 years was performed at the PubMed, Scielo, and Bireme databases. Antiphospholipid antibody syndrome may be associated with primary infertility, interfering with endometrial decidualization and with decreased ovarian reserve. Antiphospholipid antibodies also have direct negative effects on placentation, when they bind to the trophoblast, reducing their capacity for invasion, and proinflammatory effects, such as complement activation and neutrophil recruitment, contributing to placental insufficiency, restricted intrauterine growth, and fetal loss. In relation to thrombosis, APS results in a diffuse thrombotic diathesis, with global and diffuse dysregulation of the homeostatic balance. Knowing the pathophysiology of APS, which is closely linked to female infertility, is essential for new therapeutic approaches, specialized in immunomodulation and inflammatory signaling pathways, to provide important advances in its treatment.

A Síndrome do anticorpo antifosfolípide (SAF) é uma doença sistêmica, autoimune e pró-trombótica caracterizada por anticorpos antifosfolípides, trombose, aborto recorrente, complicações durante a gestação, e, ocasionalmente, trombocitopenia. O objetivo do presente estudo foi revisar a fisiopatologia da SAF e sua associação com a infertilidade feminina. Foi feita uma revisão bibliográfica dos últimos 20 anos nas bases de dados PubMed, Scielo e Bireme. A SAF pode estar associada à infertilidade primária, interferindo na decidualização endometrial e com baixas reservas ovarianas. Os anticorpos antifosfolípides também apresentam efeito negativo direto na placentação, se ligando ao trofoblasto e diminuindo sua capacidade de invasão, além de efeitos pró-inflamatórios, tais como ativação do sistema de complemento e recrutamento de neutrófilos, contribuindo para a insuficiência placentária, crescimento intrauterino restrito e perda fetal. Quanto a trombose, a SAF resulta em distúrbios trombóticos difusos, com uma desregulação do balanço homeostático. Conhecer a fisiopatologia da SAF, que apresenta associação importante com a infertilidade feminina, é essencial para novas abordagens terapêuticas, principalmente no que tange imunomodulação e os caminhos de ativação inflamatórios.

Antiphospholipid antibody syndrome and infertility / Síndrome anticorpo antifosfolípide e infertilidade

Abstract Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies (aPLs), thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. The objective of the present study was to review the pathophysiology of APS and its association with female infertility. A bibliographic review of articles of the past 20 yearswas performed at the PubMed, Scielo, and Bireme databases. Antiphospholipid antibody syndrome may be associated with primary infertility, interfering with endometrial decidualization and with decreased ovarian reserve. Antiphospholipid antibodies also have direct negative effects on placentation, when they bind to the trophoblast, reducing their capacity for invasion, and proinflammatory effects, such as complement activation and neutrophil recruitment, contributing to placental insufficiency, restricted intrauterine growth, and fetal loss. In relation to thrombosis, APS results in a diffuse thrombotic diathesis, with global and diffuse dysregulation of the homeostatic balance. Knowing the pathophysiology of APS, which is closely linked to female infertility, is essential for new therapeutic approaches, specialized in immunomodulation andinflammatory signaling pathways, to provide important advances in its treatment.

Resumo A Síndrome do anticorpo antifosfolípide (SAF) é uma doença sistêmica, autoimune e prótrombótica caracterizada por anticorpos antifosfolípides, trombose, aborto recorrente, complicações durante a gestação, e, ocasionalmente, trombocitopenia. O objetivo do presente estudo foi revisar a fisiopatologia da SAF e sua associação com a infertilidade feminina. Foi feita uma revisão bibliográfica dos últimos 20 anos nas bases de dados PubMed, Scielo e Bireme. A SAF pode estar associada à infertilidade primária, interferindo na decidualização endometrial e combaixas reservas ovarianas. Os anticorpos antifosfolípides também apresentam efeito negativo direto na placentação, se ligando ao trofoblasto e diminuindo sua capacidade de invasão, além de efeitos pró-inflamatórios, tais como ativação do sistema de complemento e recrutamento de neutrófilos, contribuindo para a insuficiência placentária, crescimento intrauterino restrito e perda fetal.Quanto a trombose, a SAF resulta em distúrbios trombóticos difusos, com uma desregulação do balanço homeostático. Conhecer a fisiopatologia da SAF, que apresenta associação importante com a infertilidade feminina, é essencial para novas abordagens terapêuticas, principalmente no que tange imunomodulação e os caminhos de ativação inflamatórios.

Intravenous Immunoglobulin Therapy in Refractory Autoimmune Dysautonomias: A Retrospective Analysis of 38 Patients.

BACKGROUND: Intravenous immunoglobulin (IVIG) has recognized efficacy in autoimmune peripheral nerve disorders, but there has been limited study of the use of IVIG in autoimmune dysautonomias. STUDY QUESTION: To determine the efficacy and safety of IVIG in patients with disabling, refractory autoimmune dysautonomias, including patients with postural tachycardia syndrome and gastrointestinal dysmotility. STUDY DESIGN: Patients with one or more autonomic disorder(s) and persistent serological evidence for autoimmunity who were unable to work or attend school despite usual treatments for dysautonomia were treated with IVIG for at least 3 months at a dose of at least 1 gm/kg monthly. MEASURES AND OUTCOMES: Outcome measures included the composite autonomic symptom scale 31 survey and a functional ability score. RESULTS: There were 38 patients, 84% female and mean age of 28.4 years. Of patients, 83.5% improved on IVIG as defined by at least 20% improvement in the composite autonomic symptom scale 31 and/or functional ability score. The mean pretreatment functional ability score was 21% (mostly bedridden), which improved to a mean of 74% (nearing able to return to work/school) for responsive patients after at least 1 year of IVIG. The mean time to the first sign of response was 5.3 weeks. There were no serious adverse events. The Mayo autoimmune dysautonomia panel antibodies and traditional Sjögren antibodies were present in only 13% and 8% of patients, respectively, but antiphospholipid antibodies and novel Sjögren antibodies were present in 76% and 42% of patients, respectively. CONCLUSIONS: There is increasing evidence that IVIG is safe and effective in a subset of patients with autonomic disorders and evidence for autoimmunity. A 4-month IVIG trial should be considered in severely affected patients who are refractory to lifestyle and pharmacological therapies. Antiphospholipid antibodies and novel Sjögren antibodies are often present in these patients and correlate with a high response rate to IVIG.

Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

Sleep disorders in primary antiphospholipid syndrome.

The objective of this study was to evaluate the sleep quality, the presence of sleep disorders in patients with primary antiphospholipid syndrome (pAPS), and their possible clinical and laboratory associations. This was a cross-sectional study of 40 consecutive pAPS patients and 211 healthy age- and sex-matched controls. Demographic and clinical data, drug use, and antiphospholipid antibodies were evaluated. Sleep was evaluated using the Pittsburgh Sleep Quality Index (PSQI). pAPS patients had significantly worse sleep quality than healthy controls. Analyzing the individual components, pAPS had worse scores in five of seven components: sleep duration (p = 0.002), habitual sleep efficiency (p = 0.003), sleep disturbance (p < 0.001), use of sleep medication (p < 0.001), and daytime somnolence (p = 0.03). No association of sleep disturbance and demographic, clinical, and laboratory features of the disease was observed. This is the first study to analyze sleep quality in pAPS. We observed that pAPS had significant worse sleep quality; however, no demographic, clinical, or laboratory feature was associated with sleep disturbance.

The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome.

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.

Serum antiphospholipid antibody levels as biomarkers for diagnosis of pulmonary tuberculosis patients.

SETTING: Salvador, Bahia, Brazil. OBJECTIVE: To evaluate the immunoglobulin (Ig)M and total IgG antibody response to cardiolipin (CL), phosphatidylcholine (PTC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and sulfatide (SL-I) as biosignatures that can be used to diagnose pulmonary tuberculosis (TB) and its applicability for monitoring the efficacy of anti-tuberculosis treatment. DESIGN: Serum samples from 37 adult pulmonary TB patients and 48 controls (16 healthy household contacts, 19 household contacts with latent tuberculous infection [LTBI] and 13 non-TB patients with lung disease) were screened using enzyme-linked immunosorbent assays (ELISAs) for IgM and total IgG against phospholipids. RESULTS: Levels of IgM response to CL, PE and PI, and IgG response to CL, PE, PI and PTC were significantly higher in TB patients than in control groups. Anti-CL IgG had the best performance characteristics, with a sensitivity and specificity of respectively 86.5% and 87.2%. This IgG anti-CL ELISA test detected 86.5% (32/37) of the TB patients, whereas the number detected using sputum smear was only 65.9% (24/37). After anti-tuberculosis treatment, the median value for all anti-phospholipid antibodies decreased significantly compared with baseline values (P < 0.05). CONCLUSION: Our results suggest that the total IgG anti-CL level could be useful to complement conventional bacteriological tests for the rapid diagnosis of adult pulmonary TB.

What is the best time to assess the antiphospholipid antibodies (aPL) profile to better predict the obstetric outcome in antiphospholipid syndrome (APS) patients?

Serological risk factors are the most important determinant in predicting unsuccessful pregnancy in obstetric antiphospholipid antibodies syndrome (OAPS) despite conventional treatment. It is not clear if changes in the profile of antiphospholipid antibodies (aPL) during pregnancy modify the risk associated with a poor response to conventional treatment. The aim of our study was to compare the value of a serological tag for aPL obtained before and during the first trimester of pregnancy to predict the response to conventional treatment. We carefully selected 97 pregnancies in women who were included in our study only if they were diagnosed with OAPS prior to a new pregnancy (basal serological risk), retested for aPL during the first trimester of pregnancy (serological risk during pregnancy), and treated with conventional therapy. High baseline serological risk was associated with pregnancy failure in 62.1% of cases (18/29) and predicted 82.5% of pregnancy outcomes with conventional treatment: OR = 16.9, CI = 5.5-52.1, p < 0.001. High serological risk during pregnancy was associated with pregnancy failure in 86.3% of cases (19/22) and predicted 91.8% of pregnancy outcomes with conventional treatment: OR = 88.7, CI = 19.4-404.8, p < 0.001. According to these results, we found that risk categorization performed during pregnancy was better in predicting pregnancy outcome (82.5 vs. 91.8%). Moreover, risk categorization during pregnancy had an increased specificity regarding the prediction: 84.9% at baseline and 95.9% during pregnancy (p = 0.024). Our findings suggest that it is important to perform aPL during the first trimester of pregnancy since that is the best time to establish the serological risk factors.

Renal Involvement in Antiphospholipid Syndrome.

Antiphospholipid syndrome is a complex autoimmune disease, characterized by the presence of vascular thrombosis, obstetric, hematologic, cutaneous, and cardiac manifestations. Renal disease in patients with antiphospholipid syndrome was not recognized in the first descriptions of the disease, but later on, the renal manifestations of the syndrome have been investigated widely. Renal manifestations of antiphospholipid syndrome conform a wide spectrum of diverse renal syndromes. Hypertension is one of the most frequent, but less commonly recognized renal alteration. It can be difficult to control as its origin is renovascular. Renal vascular thrombosis can be arterial or venous. Other alterations are renal infarction and vascular thrombosis in arterial territories. Venous thrombosis can be present in primary and secondary antiphospholipid syndrome; it presents with worsening of previous proteinuria or de novo nephrotic syndrome, hypertension and renal failure. Antiphospholipid syndrome nephropathy is a vascular disease that affects glomerular tuft, interstitial vessels, and peritubular vessels; histopathology characterizes the renal lesions as acute or chronic, the classic finding is thrombotic microangiopathy, that leads to fibrosis, tubule thyroidization, focal cortical atrophy, and glomerular sclerosis. Antiphospholipid syndrome nephropathy can also complicate patients with systemic lupus erythematosus, and there is vast information supporting the worse renal prognosis in this group of patients with the classic histopathologic lesions. Treatment consists of anticoagulation, as for other thrombotic manifestations of antiphospholipid syndrome. There is some evidence of glomerulonephritis as an isolated lesion in patients with antiphospholipid syndrome. The most frequently reported glomerulonephritis is membranous; with some reports suggesting that immunosuppressive treatment may be effective. Patients with end stage renal disease commonly are positive for antiphospholipid antibodies, but it is not clear what is the role of aPL in this setting. Patients with vascular access may have complications in the presence of antibodies so that anticoagulation is recommended. Patients ongoing renal transplant with persistent antiphospholipid antibody positivity may have early and late graft failure.