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INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism (PE) survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography (CTPA) diagnosing the index PE. METHODS: Twelve new algorithms, incorporating the CTEPH prediction score, ECG reading, NT-proBNP levels and dedicated CTPA reading were evaluated in the international InShape II (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in PE patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index (NRI) compared to the InShape II algorithm. RESULTS: The algorithm starting with CTPA reading of the index PE for 6 signs of CTEPH, followed by the ECG/NTproBNP assessment and echocardiography resulted in the most beneficial change compared to InShape II with a need for echocardiography in 20% (+5%), a failure rate of 0%, and an NRI of +3.5, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with an NRI of +6.0. CONCLUSION: Dedicated CTPA reading of the index PE improved the performance of the InShape II algorithm and may improve the selection of PE survivors who require echocardiography to rule out CTEPH.
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An accurate and prompt diagnosis of deep vein thrombosis and/or pulmonary embolism is important to prevent serious complications and mortality. Because the clinical presentation of venous thromboembolism (VTE) is often nonspecific, objective testing by means of radiological imaging is required to confirm the diagnosis. Historically, a diagnosis of VTE involved invasive imaging techniques like contrast venography or conventional pulmonary angiography. Technological developments toward more accurate and less invasive diagnostics have driven the implementation of a variety of newer technologies over the past decades, as well as the derivation and validation of clinical decision rules (CDRs) that can be used to rule out VTE in combination with D-dimer blood tests. In this narrative review, we provide a historical overview of the most notable developments in the imaging techniques and CDRs for VTE diagnosis.
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Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/historia , Tromboembolia Venosa/diagnóstico por imagen , Historia del Siglo XX , Historia del Siglo XXI , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/historia , Productos de Degradación de Fibrina-Fibrinógeno/análisisRESUMEN
INTRODUCTION: The gut microbiome is recognized as a factor that could potentially contribute to the persistent antibodies of antiphospholipid syndrome (APS). Gut microbial interventions can both induce and mitigate APS in mice. In human APS patients, anti-beta-2-glycoprotein I (ß2GP-1) titers correlate with antibody titers against a gut commensal protein homologous to ß2GP-1. AIM: To investigate the effect of the intestinal microenvironment on human APS. Methods We cross-sectionally compared intestinal microbiota composition quantified by shotgun sequencing; fecal short chain fatty acids (SCFAs), bacterial metabolites known to affect autoimmune processes; and fecal calprotectin, an intestinal inflammatory marker, in APS patients and healthy controls. RESULTS: Neither alpha nor beta diversity of the gut microbiota differed between APS patients (n = 15) and controls (n = 16) and no taxa were differentially abundant. Moreover, fecal SCFAs and fecal calprotectin, did not differ between the groups. CONCLUSION: Gut microbiome effects on the APS phenotype are likely not driven by bacterial overabundance, SCFA production or intestinal inflammation.
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The rate of identified isolated subsegmental pulmonary embolism (ssPE) has doubled with advances in computed tomography pulmonary angiography (CTPA) technology, but its clinical relevance is debated. The YEARS diagnostic algorithm was shown to safely reduce the number of required CTPAs in the diagnostic management of PE. We hypothesized that the higher threshold for performing CTPA in YEARS was associated with a lower prevalence of ssPE compared to the conventional diagnostic algorithm. We compared 2291 consecutive patients with suspected PE managed according to YEARS to 3306 consecutive control patients managed according to the Wells score for the prevalence of isolated ssPE. In the YEARS cohort, 52% were managed without CTPA, 12% had pulmonary embolism (PE) of which 10% were isolated ssPE, and the 3-month diagnostic failure rate was 0·35%. In the control cohort, 32% were managed without CTPA, 20% had PE of which 16% were isolated ssPE, and the 3-month failure rate was 0·73%. The isolated ssPE prevalence was significantly lower in YEARS (absolute difference 6·2% (95% confidence interval [CI] 1·4-10), Odds Ratio 0·58 (95% CI 0·37-0·90). In conclusion, YEARS is associated with a lower prevalence of isolated ssPE, due to reduction in CTPAs by the higher D-dimer threshold. This was however not associated with a higher risk of recurrent VTE during follow-up.
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Algoritmos , Embolia Pulmonar , Tomografía Computarizada por Rayos X , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/mortalidad , Tasa de SupervivenciaAsunto(s)
Hipertensión Pulmonar , Embolia Pulmonar , Tromboembolia , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/epidemiología , Incidencia , Tromboembolia/complicaciones , Embolia Pulmonar/complicaciones , Embolia Pulmonar/epidemiología , Enfermedad Aguda , Enfermedad CrónicaRESUMEN
BACKGROUND: Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared. OBJECTIVE: We sought to assess the effectiveness of enoxaparin in addition to high-risk care for the prevention of preeclampsia and small-for-gestational-age pregnancy in women with a history of these conditions. STUDY DESIGN: This was an open-label randomized controlled trial in 5 tertiary care centers in 3 countries. Women with a viable singleton pregnancy were invited to participate between >6+0 and <16+0 weeks if deemed to be at high risk of preeclampsia and/or small for gestational age based on their obstetric history. Eligible participants were randomly assigned in a 1-to-1 ratio to standard high-risk care or standard high-risk care plus enoxaparin 40 mg (4000 IU) by subcutaneous injection daily from recruitment until 36+0 weeks or delivery, whichever occurred sooner. Standard high-risk care was defined as care coordinated by a high-risk antenatal clinic service, aspirin 100 mg daily until 36+0 weeks, and-for women with prior preeclampsia-calcium 1000-1500 mg daily until 36+0 weeks. In a subgroup of participants serum samples were taken at recruitment and at 20 and 30 weeks' gestation and later analyzed for soluble fms-like tyrosine kinase-1, soluble endoglin, endothelin-1, placental growth factor, and soluble vascular cell adhesion molecule 1. The primary outcome was a composite of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile. All data were analyzed on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12609000699268). RESULTS: Between July 26, 2010, and Oct. 28, 2015, a total of 156 participants were enrolled and included in the analysis. In all, 149 participants were included in the outcome analysis (72 receiving standard high-risk care plus enoxaparin and 77 receiving standard high-risk care only). Seven women who miscarried <16 weeks' gestation were excluded. The majority of participants (151/156, 97%) received aspirin. The addition of enoxaparin had no effect on the rate of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile: enoxaparin 18/72 (25%) vs no enoxaparin 17/77 (22.1%) (odds ratio, 1.19; 95% confidence interval, 0.53-2.64). There was also no difference in any of the secondary outcome measures. Levels of soluble fms-like tyrosine kinase-1 and soluble endoglin increased among those who developed preeclampsia, but there was no difference in levels of these antiangiogenic factors (nor any of the other serum analytes measured) among those treated with enoxaparin compared to those receiving standard high-risk care only. CONCLUSION: The use of enoxaparin in addition to standard high-risk care does not reduce the risk of recurrence of preeclampsia and small-for-gestational-age infants in a subsequent pregnancy.
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Anticoagulantes/uso terapéutico , Enoxaparina/uso terapéutico , Retardo del Crecimiento Fetal/prevención & control , Preeclampsia/prevención & control , Adulto , Femenino , Humanos , Embarazo , Adulto JovenRESUMEN
BACKGROUND: Pulmonary embolism is a leading cause of pregnancy-related death. An accurate diagnosis in pregnant patients is crucial to prevent untreated pulmonary embolism as well as unnecessary anticoagulant treatment and future preventive measures. Applied imaging techniques might perform differently in these younger patients with less comorbidity and altered physiology, who largely have been excluded from diagnostic studies. OBJECTIVES: To determine the diagnostic accuracy of computed tomography pulmonary angiography (CTPA), lung scintigraphy and magnetic resonance angiography (MRA) for the diagnosis of pulmonary embolism during pregnancy. SEARCH METHODS: We searched MEDLINE and Embase until July 2015. We used included studies as seeds in citations searches and in 'find similar' functions and searched reference lists. We approached experts in the field to help us identify non-indexed studies. SELECTION CRITERIA: We included consecutive series of pregnant patients suspected of pulmonary embolism who had undergone one of the index tests (computed tomography (CT) pulmonary angiography, lung scintigraphy or MRA) and clinical follow-up or pulmonary angiography as a reference test. DATA COLLECTION AND ANALYSIS: Two review authors performed data extraction and quality assessment. We contacted investigators of potentially eligible studies to obtain missing information. In the primary analysis, we regarded inconclusive index test results as a negative reference test, and treatment for pulmonary embolism after an inconclusive index test as a positive reference test. MAIN RESULTS: We included 11 studies (four CTPA, five lung scintigraphy, two both) with a total of 695 CTPA and 665 lung scintigraphy results. Lung scintigraphy was applied by different techniques. No MRA studies matched our inclusion criteria.Overall, risk of bias and concerns regarding applicability were high in all studies as judged in light of the review research question, as was heterogeneity in study methods. We did not undertake meta-analysis. All studies used clinical follow-up as a reference standard, none in a manner that enabled reliable identification of false positives. Sensitivity and negative predictive value were therefore the only valid test accuracy measures.The median negative predictive value for CTPA was 100% (range 96% to 100%). Median sensitivity was 83% (range 0% to 100%).The median negative predictive value for lung scintigraphy was 100% (range 99% to 100%). Median sensitivity was 100% (range 0% to 100%).The median frequency of inconclusive results was 5.9% (range 0.9% to 36%) for CTPA and 4.0% (range 0% to 23%) for lung scintigraphy. The overall median prevalence of pulmonary embolism was 3.3% (range 0.0% to 8.7%). AUTHORS' CONCLUSIONS: Both CTPA and lung scintigraphy seem appropriate for exclusion of pulmonary embolism during pregnancy. However, the quality of the evidence mandates cautious adoption of this conclusion. Important limitations included poor reference standards, necessary assumptions in the analysis regarding inconclusive test results and the inherent inability of included studies to identify false positives. It is unclear which test has the highest accuracy. There is a need for direct comparisons between diagnostic methods, including MR, in prospective randomized diagnostic studies.
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Tomografía de Emisión de Positrones/normas , Complicaciones Hematológicas del Embarazo/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/normas , Angiografía/normas , Angiografía/estadística & datos numéricos , Femenino , Humanos , Angiografía por Resonancia Magnética , Tomografía de Emisión de Positrones/estadística & datos numéricos , Embarazo , Cintigrafía/normas , Cintigrafía/estadística & datos numéricos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/estadística & datos numéricosRESUMEN
Background The origin of autoantibodies in patients with antiphospholipid syndrome (APS) is unknown. The gut microbiome contributes to autoimmunity and contains peptide homologues to the main APS autoantigen, which affect disease activity in animal models. Alteration of the gut microbiota with vancomycin diminishes disease activity in mice but no data on the effect of gut microbiota alteration in APS patients are available to date. Objective To evaluate whether the gut microbiome affects disease activity in human APS. Methods This was a pre-post design intervention study in APS patients with stable disease and no gastrointestinal comorbidity. Subjects received oral vancomycin, 500 mg four times daily for 7 days, previously shown to alter gut microbiota composition without systemic effects. Disease activity was assessed at four time points by measuring a panel of clinical phenotype-related biomarkers: antiphospholipid antibodies (APLAs), complement and inflammation markers, and hemostatic parameters. The primary outcome was the composite of the biomarker panel determined by multilevel principal component analysis. Results A total of 15 subjects completed the study. The primary outcome, the first principal component of the biomarker panel data, was significantly different after 7 days of vancomycin treatment ( p = 0.03), but not at day 42. APLA titers were unaffected. Unexpectedly, 4 out of 15 patients were negative for APLAs at baseline. In a post-hoc analysis, there was a prolonged effect for subjects with positive antibodies at baseline ( p = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. Conclusion The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.
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Background The noninvasive magnetic resonance direct thrombus imaging (MRDTI) technique can be used to diagnose acute deep vein thrombosis (DVT), without the use of intravenous contrast. MRDTI holds the potential to differentiate between acute and chronic DVT and could be helpful when diagnosing thrombosis is challenging. Objectives Our objective was to evaluate the application of MRDTI in clinical practice, including the frequency and indications of MRDTI scans performed in practice-based conditions, results, impact on treatment decisions, and associated patient outcomes. Methods A retrospective study was performed at the Leiden University Medical Center, the Netherlands. MRDTI scans performed since its implementation in patients aged ≥18 years as part of clinical practice for the diagnostic management of suspected thrombosis were evaluated. Results Between October 2015 and September 2023, 36 patients had undergone MRDTI for the diagnostic evaluation of thrombosis. MRDTI application increased since 2019 (five-eight scans per year). The most common indication was to differentiate between acute and chronic thrombosis, mainly for suspected recurrent ipsilateral DVT after inconclusive compression ultrasonography. In over a third of patients, acute thrombosis was confirmed by MRDTI. MRDTI results determined treatment decisions in all except two patients. One patient had symptomatic thrombosis of the lower extremity within 3 months after an MRDTI of the upper extremity without signs of acute thrombosis (1/23; 4.3%, 95% confidence interval: 0.77-21). Conclusion Over the past 4 years, MRDTI has been used increasingly in our hospital. MRDTI results guided treatment decisions, which confirms the clinical impact and feasibility of its application in daily practice.
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Antiphospholipid syndrome (APS) is an auto-immune syndrome defined by thrombosis and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies. Antiphospholipid antibodies are a group of antibodies predominantly directed at phospholipid-bound plasma proteins. The more antibodies a patient has the higher the risk of thrombosis. The origin of the antibodies and the precise prothrombotic mechanism are incompletely understood. A diagnosis of APS can in certain clinical scenarios implicate a longer treatment with anticoagulants after a venous thromboembolism. High level evidence is absent. In addition, APS patients with a high risk antibody profile had a higher risk of arterial thrombosis in randomized trials when treated with direct oral anticoagulants compared to vitamin K antagonists. The number needed to screen in light of these possible consequences of an APS diagnosis for treatment, appears to high to justify routine screening. In this review we suggest indications for APS testing in the context of venous thromboembolism.
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Síndrome Antifosfolípido , Trombosis , Tromboembolia Venosa , Embarazo , Femenino , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Anticoagulantes/uso terapéutico , Anticuerpos Antifosfolípidos/uso terapéutico , Trombosis/prevención & controlRESUMEN
When confronted with an unexpected clinical observation, such as a remarkable symptom in a patient with an unrelated rare disease, clinicians increasingly apply online literature search to support the observed correlation. Against a background of an exponential rise in medical publications and the well-documented problem of publication bias, the easy access to literature carries the risk of suggesting spurious correlations. The current paper expounds on this phenomenon. Queries in medical search engines often provide a number of hits, regardless of the plausibility of the correlation searched for. To quantify this, we recently performed a study involving 30.000 automated queries in PubMed using completely random search terms drawn from lists of diseases, symptoms and medications. This provided a background rate of PubMed hits. The data support that several hits by no means automatically indicate a relevant correlation, and underline need for judicious critical appraisal when searching for a correlation observed in daily practice.
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Internet , Enfermedades Raras , Motor de Búsqueda , HumanosRESUMEN
INTRODUCTION: Acute pulmonary embolism (PE) is a disease with a broad spectrum of clinical presentations. While some patients can be treated at home or may even be left untreated, other patients require an aggressive approach with reperfusion treatment. AREAS COVERED: (1) Advanced reperfusion treatment in hemodynamically stable acute PE patients considered to be at high risk of decompensation and death, (2) the treatment of subsegmental pulmonary embolism, (3) outpatient treatment for hemodynamically stable PE patients with signs of right ventricle (RV) dysfunction, and (4) the optimal approach to identify and treatpost-PE syndrome. EXPERT OPINION: Outside clinical trials, hemodynamically stable acute PE patients should not be treated with primary reperfusion therapy. Thrombolysis and/or catheter-directed therapy are only to be considered as rescue treatment. Subsegmental PE can be left untreated in selected low-risk patients, after proximal deep vein thrombosis has been ruled out. Patients with an sPESI or Hestia score of 0 criteria can be treated at home, independent of the presence of RV overload. Finally, health-care providers should be aware of post-PE syndrome and diagnose chronic thromboembolic pulmonary disease (CTEPD) as early as possible. Persistently symptomatic patients without CTEPD benefit from exercise training and cardiopulmonary rehabilitation.
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Embolia Pulmonar , Humanos , Resultado del Tratamiento , Embolia Pulmonar/terapia , Embolia Pulmonar/tratamiento farmacológico , Enfermedad AgudaRESUMEN
BACKGROUND: The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison. OBJECTIVES: To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients. METHODS: Patient-level data (n = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared. RESULTS: All six scenarios including reference CUS had higher estimated 1-year costs (1,763-1,913) than the six without reference CUS (1,192-1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS. CONCLUSION: One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS.
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The antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity. The manifestations are caused by antibodies targeting cell membrane phospholipids and/or associated proteins. The triggers leading to these antibodies' production are unknown but recent work suggests cross-reactivity between the autoantigens and peptides produced by the intestinal microbiome. Work on how the autoantibodies could cause clinical manifestations implicates different mechanisms. Binding to surface proteins of different cell types can induce intracellular signaling leading to cell activation and tissue factor expression. Complement activation and neutrophil extracellular-traps are also involved, and recent evidence implicates endothelial protein C receptor-lysobisphosphatidic acid complex. Pregnancy is a high-risk situation for antiphospholipid syndrome patients due to the increased risk of thrombosis and obstetric complications. Epidemiological and clinical research on APS is hampered by heterogeneity in populations, testing and treatment strategies. About one in 10 to one in fifty APS pregnancies is complicated by thrombosis, despite treatment. Pregnant patients with prior thrombosis are prescribed therapeutic dose heparins and low dose aspirin. Without prior thrombosis a prophylactic dose is used. The most frequent obstetrical manifestation is recurrent early pregnancy loss. The association of APS antibodies with late pregnancy loss is stronger, however. Prevention of recurrence is achieved with aspirin and prophylactic dose heparin, although the evidence is of low certainty. The third obstetrical classifying manifestation comprises preterm delivery due to placenta-mediated complications and is treated in subsequent pregnancies with aspirin with or without prophylactic dose heparin, again based on low quality evidence. New therapies are under investigation.
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The antiphospholipid syndrome (APS) is a thrombotic autoimmune disease in which the origin of the disease-characterizing autoantibodies is unknown. Increased research effort into the role of the intestinal microbiome in autoimmunity has produced new insights in this field. This scoping review focusses on the gut microbiome in its relation to APS. EMBASE and MEDLINE were searched for original studies with relevance to the relation between the gut microbiome and APS. Thirty studies were included. Work on systemic lupus erythematosus, which strongly overlaps with APS, has shown that patients often display an altered gut microbiome composition, that the disease is transferable with the microbiome, and that microbiome manipulation affects disease activity in murine lupus models. The latter has also been shown for APS, although data on microbiome composition is less consistent. APS patients do display an altered intestinal IgA response. Evidence has accrued for molecular mimicry as an explanatory mechanism for these observations in APS and other autoimmune diseases. Specific gut microbes express proteins with homology to immunodominant APS autoantigens. The disease phenotype appears to be dependent on these mimicking proteins in an APS mouse model, and human APS B- and T-cells indeed cross-react with these mimics. Pre-clinical evidence furthermore suggests that diet may influence autoimmunity through the microbiome, as may microbial short chain fatty acid production, though this has not been studied in APS. Lastly, the microbiome has been shown to affect key drivers of thrombosis, and may thus affect APS severity through non-immunological mechanisms. Overall, these observations demonstrate the impact of the intestinal microbiome on autoimmunity and the importance of understanding its role in APS.
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Síndrome Antifosfolípido , Enfermedades Autoinmunes , Microbioma Gastrointestinal , Microbiota , Humanos , Ratones , Animales , AutoinmunidadRESUMEN
The gut microbiome affects the development and progress of various types of disease such as obesity, diabetes, atherosclerosis and arterial thrombosis. Gut microbiome derived metabolites have been established to be predictive of arterial thrombosis in epidemiological studies. In these studies atherosclerosis and prothrombotic effect cannot be distinguished but preclinical studies show gut derived metabolites can induce platelet hyperreactivity and increase thrombotic potential. Gut commensals can also influence platelets through serotonin synthesis and may enhance Von Willebrand factor production. The effects on secondary haemostasis are less studied. In antiphospholipid syndrome, a thrombotic auto-immune disorder, autoreactive T cells and antibodies cross-react with auto-antigen mimicking peptides from gut commensals which appears to contribute to the pathophysiology. This review focusses on the prothrombotic effect of the gut microbiome and aims to provide insight into its influence on thromboembolic disease and the haemostatic system.
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Aterosclerosis , Enfermedades Cardiovasculares , Diabetes Mellitus , Microbioma Gastrointestinal , Enfermedades Cardiovasculares/etiología , Humanos , ObesidadRESUMEN
BACKGROUND: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans. METHODS: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty-five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards. RESULTS: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation, however, and proteins did not cluster according to an apparent biological grouping. DISCUSSION: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications.