Obstetric APS and thrombosis; modelling future risks.
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ABSTRACT:
SUBMITTER: Spaanderman M
PROVIDER: S-EPMC6594133 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Obstetric APS and thrombosis; modelling future risks.
Spaanderman M M Ghossein-Doha C C
BJOG : an international journal of obstetrics and gynaecology 20190206 5
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Project description:ObjectiveTo 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.DesignRetrospective study.SettingThe Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository.PopulationWomen with Ob-APS.MethodsComparison 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 measuresRisk factors for thrombosis and aGAPSS.ResultsOf 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].ConclusionBased 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 abstractMore than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.
| S-EPMC7382947 | biostudies-literature
Project description:Malignancies can be associated with positive antiphospholipid antibodies but the incidence of cancer among women with the purely obstetric form of antiphospholipid syndrome (APS) is currently unknown. Our aim was to investigate the comparative incidence of cancers in women with a history of obstetric APS within a referral university hospital-based cohort (NOH-APS cohort). We performed a 17-year observational study of 1,592 non-thrombotic women with three consecutive spontaneous abortions before the 10th week of gestation or one fetal death at or beyond the 10th week of gestation. We compared the incidence of cancer diagnosis during follow-up among the cohort of women positive for antiphospholipid antibodies (n=517), the cohort of women carrying the F5 rs6025 or F2 rs1799963 polymorphism (n=279) and a cohort of women with negative thrombophilia screening results (n=796). The annualized rate of cancer was 0.300% (0.20%-0.44%) for women with obstetric APS and their cancer risk was substantially higher than that of women with negative thrombophilia screening [adjusted hazard ratio (aHR) 2.483; 95% confidence interval (CI) 1.27-4.85]. The computed standardized incidence ratio for women with obstetric APS was 2.89; 95% CI: 1.89-4.23. Among antiphospholipid antibodies, lupus anticoagulant was associated with incident cancers (aHR 2.608; 95% CI: 1.091-6.236). Our cohort study shows that the risk of cancer is substantially higher in women with a history of obstetric APS than in the general population, and in women with a similar initial clinical history but negative for antiphospholipid antibodies.
| S-EPMC7012495 | biostudies-literature
Project description:The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies, including anti-β2-glycoprotein-I (anti-β2GPI), that are considered central to APS pathogenesis. Based on animal studies showing a role of complement in APS-related clinical events, we used the modified Ham (mHam) assay (complement-dependent cell killing) and cell-surface deposition of C5b-9 to test the hypothesis that complement activation is associated with thrombotic events in APS. A positive mHam (and corresponding C5b-9 deposition) were present in 85.7% of catastrophic APS (CAPS), 35.6% of APS (and 68.5% of samples collected within 1 year of thrombosis), and only 6.8% of systemic lupus erythematosus (SLE) sera. A positive mHam assay was associated with triple positivity (for lupus anticoagulant, anticardiolipin, and anti-β2GPI antibodies) and recurrent thrombosis. Patient-derived anti-β2GPI antibodies also induced C5b-9 deposition, which was blocked completely by an anti-C5 monoclonal antibody, but not by a factor D inhibitor, indicating that complement activation by anti-β2GPI antibodies occurs primarily through the classical complement pathway. Finally, patients with CAPS have high rates of rare germline variants in complement regulatory genes (60%), compared with patients with APS (21.8%) or SLE (28.6%) or normal controls (23.3%), and have mutations at a rate similar to that of patients with atypical hemolytic uremic syndrome (51.5%). Taken together, our data suggest that anti-β2GPI antibodies activate complement and contribute to thrombosis in APS, whereas patients with CAPS have underlying mutations in complement regulatory genes that serve as a "second hit," leading to uncontrolled complement activation and a more severe thrombotic phenotype.
| S-EPMC6978159 | biostudies-literature
Project description:We carried out a residual stress distribution analysis in a APS TBC throughout the depth of the coatings. The samples were heat treated at 1150 °C for 190 h and the data analysis used image based modelling based on the real 3D images measured by Computed Tomography (CT). The stress distribution in several 2D slices from the 3D model is included in this paper as well as the stress distribution along several paths shown on the slices. Our analysis can explain the occurrence of the "jump" features near the interface between the top coat and the bond coat. These features in the residual stress distribution trend were measured (as a function of depth) by high-energy synchrotron XRD (as shown in our related research article entitled 'Understanding the Residual Stress Distribution through the Thickness of Atmosphere Plasma Sprayed (APS) Thermal Barrier Coatings (TBCs) by high energy Synchrotron XRD; Digital Image Correlation (DIC) and Image Based Modelling') (Li et al., 2017) [1].
| S-EPMC5496202 | biostudies-literature
Project description:ObjectiveTo investigate whether prepregnancy obesity is associated with adverse pregnancy outcomes among women without chronic disease.MethodsSingleton deliveries (N=112,309) among mothers without chronic diseases in the Consortium on Safe Labor, a retrospective U.S. cohort, were analyzed using Poisson regression with robust variance estimation. Relative risks and 95% confidence intervals (CIs) estimated perinatal risks in relation to prepregnancy obesity status adjusted for age, race-ethnicity, parity, insurance, smoking and alcohol use during pregnancy, and study site.ResultsObstetric risks were variably (and mostly marginally) increased as body mass index (BMI) category and obesity class increased. In particular, the risk of gestational hypertensive disorders, gestational diabetes, cesarean delivery, and induction increased in a dose-response fashion. For example, the percentage of gestational diabetes among obese class III women was 14.6% in contrast to 2.8% among women with normal BMIs (corresponding relative risks [95% CI] 1.99 [1.86-2.13], 2.94 [2.73-3.18], 3.97 [3.61-4.36], and 5.47 [4.96-6.04] for overweight, obese class I, obese class II, and obese class III women, respectively) compared with women with normal BMIs. Similarly, neonatal risks increased in a dose-response fashion with maternal BMI status including preterm birth at less than 32 weeks of gestation, large for gestational age (LGA), transient tachypnea, sepsis, and intensive care unit admission. The percentage of LGA neonates increased from 7.9% among women with normal BMIs to 17.3% among obese class III women and relative risks increased to 1.52 (1.45-1.58), 1.74 (1.65-1.83), 1.93 (1.79-2.07), and 2.32 (2.14-2.52) as BMI category increased.ConclusionPrepregnancy obesity is associated with increased risks of a wide range of adverse pregnancy and neonatal outcomes among women without chronic diseases.
| S-EPMC4917420 | biostudies-literature
Project description:Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are often detected in patients with antiphospholipid syndrome (APS), but how aPS/PT engage prothrombin at the molecular level remains unknown. Here, the antigenic determinants of immunoglobulin G aPS/PT were investigated in 24 triple-positive APS patients at high risk of thrombosis by using prothrombin mutants biochemically trapped in closed and open conformations, and relevant fragments spanning the entire length of prothrombin. Two novel unexpected findings emerged from these studies. First, we discovered that some aPS/PT are unique among other anti-prothrombin antibodies insofar as they efficiently recognize prothrombin in solution after a conformational change requiring exposure of fragment-1 to the solvent. Second, we identified and characterized 2 previously unknown subpopulations of aPS/PT, namely type I and type II, which engage fragment-1 of prothrombin at different epitopes and with different mechanisms. Type I target a discontinuous density-dependent epitope, whereas type II engage the C-terminal portion of the Gla-domain, which remains available for binding even when prothrombin is bound to the phospholipids. Based on these findings, APS patients positive for aPS/PT were classified into 2 groups, group A and group B, according to their autoantibody profile. Group A contains mostly type I antibodies whereas group B contains both type I and type II antibodies. In conclusion, this study offers a first encouraging step toward unveiling the heterogeneity of anti-prothrombin antibodies in correlation with thrombosis, shedding new light on the mechanisms of antigen-autoantibody recognition in APS.
| S-EPMC6560356 | biostudies-literature
Project description:Background and purposeCerebral venous thrombosis (CVT) is a rare but life-threatening disease. Timely and proper treatments are the keys in saving patients' life and preventing from permanent neurological deficits. We performed this network meta-analysis to evaluate the role of anticoagulation in CVT, especially for the patients accompanied with hemorrhagic stroke.MethodsPubMed, Embase, Web of Science, Cochrane Database, and Chinese Biomedical (CBM) databases were searched comprehensively to select eligible articles (up to 30 June 2017). Network meta-analysis was performed based on classical frequency statistics.ResultsAround 14 studies comprising 1135 cases were included. Overall analysis showed that low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) were more effective (LMWH vs placebo: OR 4.76, 95%CI: 2.56-8.33; UFH vs placebo: OR 4.12, 95%CI: 2.17-8.33), and safe (LMWH vs placebo: OR 0.22, 95%CI: 0.069-0.65; UFH vs placebo: OR 0.28, 95%CI: 0.058-0.99) than placebo in the management of CVT. Besides, LMWH showed more advantages than UFH; As for the patients accompanied with hemorrhagic stroke, LMWH and UFH were also better than placebo (efficacy: LMWH vs placebo: OR 20, 95%CI: 5.56-100; UFH vs placebo: OR 12.5, 95%CI: 3.7-33.3; safety: LMWH vs placebo: OR 0.18, 95%CI: 0.04-0.77; UFH vs placebo: OR 0.16, 95%CI: 0.04-0.6) in the management of CVT. In addition, LMWH was more effective than UFH for the patients accompanied with hemorrhagic stroke.ConclusionAnticoagulant treatment with heparin is safe and beneficial for patients with CVT, even for those accompanied with hemorrhagic stroke. Besides, LMWH is better than UFH in the management of CVT.
| S-EPMC5976280 | biostudies-literature
Project description:Most physicians believe they practiced personalized medicine prior to the genomics era that followed the sequencing of the human genome. The focus of personalized medicine has been primarily genomic medicine, wherein it is hoped that the nucleotide dissimilarities among different individuals would provide clinicians with more precise understanding of physiology, more refined diagnoses, better disease risk assessment, earlier detection and monitoring, and tailored treatments to the individual patient. However, to date, the "genomic bench" has not worked itself to the clinical thrombosis bedside. In fact, traditional plasma-based hemostasis-thrombosis laboratory testing, by assessing functional pathways of coagulation, may better help manage venous thrombotic disease than a single DNA variant with a small effect size. There are some new and exciting discoveries in the genetics of platelet reactivity pertaining to atherothrombotic disease. Despite a plethora of genetic/genomic data on platelet reactivity, there are relatively little actionable pharmacogenetic data with antiplatelet agents. Nevertheless, it is crucial for genome-wide DNA/RNA sequencing to continue in research settings for causal gene discovery, pharmacogenetic purposes, and gene-gene and gene-environment interactions. The potential of genomics to advance medicine will require integration of personal data that are obtained in the patient history: environmental exposures, diet, social data, etc. Furthermore, without the ritual of obtaining this information, we will have depersonalized medicine, which lacks the precision needed for the research required to eventually incorporate genomics into routine, optimal, and value-added clinical care.
| S-EPMC4891951 | biostudies-literature
Project description:Rising consumer demand is driving concerns around the "availability" and "criticality" of metals. Methodologies have emerged to assess the risks related to global metal supply. None have specifically examined the initial supply source: the mine site where primary ore is extracted. Environmental, social, and governance ("ESG") risks are critical to the development of new mining projects and the conversion of resources to mine production. In this paper, we offer a methodology that assesses the inherent complexities surrounding extractives projects. It includes eight ESG risk categories that overlay the locations of undeveloped iron, copper, and aluminum orebodies that will be critical to future supply. The percentage of global reserves and resources that are located in complex ESG contexts (i.e., with four or more concurrent medium-to-high risks) is 47% for iron, 63% for copper, and 88% for aluminum. This work contributes to research by providing a more complete understanding of source level constraints and risks to supply.
| S-EPMC9936542 | biostudies-literature