Thrombosis and haemostasis最新文献

Background:  The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy.

Methods and results:  Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69-0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69-0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74-1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79-1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy.

Conclusion:  In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.

Objective:  Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.

Material and methods:  We used two mouse models (Fbn1C1041G and Fbn1mgR ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of Efemp2 and three CRISPR/Cas9-engineered knock-in models (Ltbp1, Mfap4, and Timp1). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.

Results:  The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the Ltbp1, Mfap4, and Timp1 knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.

Conclusion:  Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) was recognized around 2 years ago, at the beginning of the anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination campaign, as a rare but life-threatening complication of adenoviral vector vaccines. Two years later, the coronavirus disease 2019 (COVID-19) pandemic has been tamed, although not defeated, and the vaccines provoking VITT have been abandoned in most high-income countries, thus why should we still speak about VITT? Because a significant fraction of the world population has not been vaccinated yet, especially in low/middle-income countries that can only afford adenoviral vector-based vaccines, because the adenoviral vector platform is being used for the development of a large series of new vaccines for other transmissible diseases, and lastly because there are some clues suggesting that VITT may not be exclusive to anti-SARS-CoV-2 vaccines. Therefore, a deep understanding of this new syndrome is highly warranted as well as the awareness that we still miss some crucial insight into its pathophysiology and on some aspects of its management. This snapshot review aims to portray our knowledge on VITT, focusing on its clinical presentation, pathophysiological insight, diagnostic and management strategies, and to pinpoint the main unmet needs, highlighting the aspects on which research should focus in the near future.

Background:  Venous thromboembolism (VTE) is a well-documented complication of both solid and hematologic malignancies, but there are fewer data on allogeneic hematopoietic cell transplant (HCT) recipients. Therefore, we studied the incidence, risk factors, and impact of VTE on post-HCT outcomes in a contemporary cohort.

Methods:  We retrospectively reviewed patients who underwent allogeneic HCT between January 2014 and August 2019 to identify patients with post-HCT VTE. Patient, disease, and transplant-related risk factors for VTE were investigated using competing risk analysis.

Results:  A total of 431 patients were included in this study. Median (interquartile range [IQR]) age in years was 59 (46-65) at transplant. The most common indication for transplant was acute myelogenous leukemia (49.4%). Within our cohort, 64 patients (14.8%) developed post-HCT VTE with a median (IQR) follow-up time of 24.6 (8.4-47.1) months. The cumulative incidence of VTE was 4.2% at 6 months, 9.0% at 12 months, 12.6% at 24 months, and 13.8% at 36 months. In multivariable analysis, older age (hazard ratio [HR] per 10-year increase: 1.36, 95% confidence interval [CI]: 1.09-1.70), history of VTE (HR: 1.95, 95% CI: 1.09-3.49), and grade 2-4 acute graft versus host disease (GVHD; HR: 1.75, 95% CI: 1.05-2.94) were independently associated with VTE. VTE was significantly associated with an increased risk of nonrelapse mortality (NRM; HR: 4.09, 95% CI: 2.47-6.74) and decreased overall survival (OS; HR: 2.19, 95% CI: 1.48-3.24).

Conclusion:  VTE is an important complication after allogeneic HCT and is significantly associated with increased NRM and decreased OS. Older patients, those with prior VTE, and patients with acute GVHD are at increased risk for development of VTE after HCT.

Background:  Sepsis-induced coagulopathy (SIC) is a common cause of poor prognosis in critically ill patients in the intensive care unit (ICU). However, currently there are no tools specifically designed for predicting the occurrence of SIC in septic patients earlier. This study aimed to develop a predictive nomogram incorporating clinical markers and scoring systems to individually predict the probability of SIC in septic patients.

Methods:  Patients consecutively recruited in the stage between January 2022 and April 2023 constituted the development cohort for retrospective analysis to internally test the nomogram, and patients in the stage between May 2023 to November 2023 constituted the validation cohort for prospective analysis to externally validate the nomogram. Univariate logistic regression analysis of the development cohort was performed firstly, and then multivariate logistic regression analysis was performed using backward stepwise method to determine the best-fitting model and obtain the nomogram from it. The nomogram was validated in an independent external validation cohort, involving discrimination and calibration. A decision curve analysis was also performed to evaluate the net benefit of the insertion decision with this nomogram.

Results:  A total of 548 and 245 patients, 55.1 and 49.4% with SIC occurrence, were included in the development and validation cohorts, respectively. Predictors contained in the prediction nomogram included shock, platelets, and international normalized ratio (INR). Patients with shock (odds ratio [OR]: 4.499; 95% confidence interval [CI]: 2.730-7.414; p < 0.001), higher INR (OR: 349.384; 95% CI: 62.337-1958.221; p < 0.001), and lower platelet (OR: 0.985; 95% CI: 0.982-0.988; p < 0.001) had higher probabilities of SIC. The development model showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.879 (95% CI: 0.850-0.908) and good calibration. Application of the nomogram in the validation cohort also gave good discrimination with an AUROC of 0.872 (95% CI: 0.826-0.917) and good calibration. The decision curve analysis of the nomogram provided better net benefit than the alternate options (intervention or no intervention).

Conclusion:  By incorporating shock, platelets, and INR in the model, this useful nomogram could be accessibly utilized to predict SIC occurrence in septic patients. However, external validation is still required for further generalizability improvement of this nomogram.

Background:  We sought to examine the dose-response relationship between high-density lipoprotein cholesterol (HDL-C) and bleeds in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI).

Methods:  All the 15,250 participants were from the Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, which is a large, single-center, prospective cohort study based on case records and a follow-up registry performed in the First Affiliated Hospital of Xinjiang Medical University from December 2016 to October 2021. We divided all the patients into five groups according to their HDL-C levels: the ≤35 mg/dL group (n = 4,732), 35 to 45 mg/dL group (n = 6,049), 45 to 55 mg/dL group (n = 2,826), 55 and 65 mg/dL group (n = 1,117), and >65 mg/dL group (n = 526). The incidence of bleeds, mortality, ischemic events, and net adverse clinical events (NACEs) among the five groups was compared.

Results:  A total of 713 bleeds, 1,180 ischemic events, 456 deaths, and 1,893 NACEs were recorded during the up to 60-month follow-up period. After adjusting for confounders, we observed a nonlinear relation for bleeds, with the highest risk at intermediate HDL-C levels (45-55 mg/dL). We also identified a dose-response relationship for ischemic events. A threshold value of HDL-C ≤35 mg/dL (adjusted hazard ratio = 0.560, 95% confidence interval: 0.360-0.872, p = 0.010) was associated with a decreased risk for bleeds in the multivariable Cox regression model. The results were consistent in multiple sensitivity analyses and propensity score-matching analysis.

Conclusion:  In the present study, a nonlinear association was identified between HDL-C levels and bleeds in CAD patients who underwent PCI, with a higher risk at intermediate levels. However, further multicenter studies are warranted.

Background:  Disruptions in the pathways for activating and deactivating proteases in the bloodstream can lead to thrombosis and bleeding issues. Leucine aminopeptidases (LAPs), which are exopeptidases essential for regulating protein and peptide activities, are recognized as clinical biomarkers for liver diseases. However, the relationship between serum LAP activity and the risks of bleeding or thrombosis, as well as the identification of the specific tissues or organs that control LAP levels, is not well understood.

Methods:  We performed a retrospective study to evaluate serum LAP activities in 149,360 patients with 47 different diseases and 9,449 healthy individuals. The analysis was conducted using SPSS V2.6, RStudio V.1.3.1073, and libraries in Python 3.8.

Results:  Our research revealed that 21 of the 47 diseases studied showed increased median serum LAP activities, while 26 diseases were associated with significantly lower activities, especially those related to thrombosis. Furthermore, most diseases were found to have an increased risk of bleeding and thrombosis, indicated by higher Q25 and lower Q75 LAP activities compared to the control group. Receiver operating characteristic curve analysis confirmed the effectiveness of LAP activities as biomarkers for specific conditions like hepatic encephalopathy, liver cancer, pancreatitis, and pancreatic cancer. Diseases were categorized into clusters with similar bleeding or thrombotic tendencies through principal component analysis.

Conclusion:  This study highlighted regulatory influence of the liver and pancreas on LAP levels. The established link between serum LAP concentrations and the risk of bleeding or thrombosis paved the way for the development of diagnostic and preventative approaches for various medical conditions.

Endothelial dysfunctions together with a dysregulated immune response and lipid accumulation are important confounding factors in the onset and chronic development of atherosclerosis. Recently, a large body of data has emerged on the sequential involvement of different immune cell types, including monocytes, in the pathology of this disease. In this condensed review, we aim to highlight some of the recent basic research and clinical findings on monocyte subsets published since our joint European Society of Cardiology consensus document, and re-evaluate their potential relevance as surrogate biomarkers in coronary artery disease.