38 research outputs found
Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society
This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control
Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study
BACKGROUND: Due to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE).
METHODS AND RESULTS: The Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium.
CONCLUSIONS: Regardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future
An update on the global use of risk assessment models and thromboprophylaxis in hospitalized patients with medical illnesses from the World Thrombosis Day steering committee: Systematic review and meta-analysis
INTRODUCTION
Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) multinational cross-sectional study reported that only approximately 40% of medical patients at risk of VTE received adequate thromboprophylaxis.
METHODS
In our systematic review and meta-analysis, we aimed at providing updated figures concerning the use of thromboprophylaxis globally. We focused on: (a) the frequency of patients with an indication to thromboprophylaxis according with individual models; (b) the use of adequate thromboprophylaxis; and (c) reported contraindications to thromboprophylaxis. Observational nonrandomized studies or surveys focusing on medically ill patients were considered eligible.
RESULTS
After screening, we included 27Â studies from 20 countries for a total of 137Â 288 patients. Overall, 50.5% (95% confidence interval [CI]: 41.9-59.1, I 99%) of patients had an indication to thromboprophylaxis: of these, 54.5% (95% CI: 46.2-62.6, I 99%) received adequate thromboprophylaxis. The use of adequate thromboprophylaxis was 66.8% in Europe (95% CI: 50.7-81.1, I 98%), 44.9% in Africa (95% CI: 31.8-58.4, I 96%), 37.6% in Asia (95% CI: 25.7-50.3, I 97%), 58.3% in South America (95% CI: 31.1-83.1, I 99%), and 68.6% in North America (95% CI: 64.9-72.6, I 96%). No major differences in adequate thromboprophylaxis use were found across risk assessment models. Bleeding, thrombocytopenia, and renal/hepatic failure were the most frequently reported contraindications to thromboprophylaxis.
CONCLUSIONS
The use of anticoagulants for VTE prevention has been proven effective and safe, but thromboprophylaxis prescriptions are still unsatisfactory among hospitalized medically ill patients around the globe with marked geographical differences
Platelet-Derived Microparticles From Obese Individuals: Characterization of Number, Size, Proteomics, and Crosstalk With Cancer and Endothelial Cells
Rationale: Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not yet completely clarified.Objectives: We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and non-obese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of (i) genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and (ii) cyclooxygenase (COX)-2 involved in the production of angiogenic and inflammatory mediators.Methods and Results: MPs were obtained from thrombin activated platelets of four obese and their matched non-obese women. MPs were analyzed by cytofluorimeter and protein content by liquid chromatography-mass spectrometry. MPs from obese women were not different in number but showed increased heterogeneity in size. In obese individuals, MPs containing mitochondria (mitoMPs) expressed lower CD41 levels and increased phosphatidylserine associated with enhanced Factor V representing a signature of a prothrombotic state. Proteomics analysis identified 44 proteins downregulated and three upregulated in MPs obtained from obese vs. non-obese women. A reduction in the proteins of the α-granular membrane and those involved in mitophagy and antioxidant defenses-granular membrane was detected in the MPs of obese individuals. MPs released from platelets of obese individuals were more prone to induce the expression of marker genes of EMT and EndMT when incubated with human colorectal cancer cells (HT29) and human cardiac microvascular endothelial cells (HCMEC), respectively. A protein, highly enhanced in obese MPs, was the pro-platelet basic protein with pro-inflammatory and tumorigenic actions. Exclusively MPs from obese women induced COX-2 in HCMEC.Conclusion: Platelet-derived MPs of obese women showed higher heterogeneity in size and contained different levels of proteins relevant to thrombosis and tumorigenesis. MPs from obese individuals presented enhanced capacity to cause changes in the expression of EMT and EndMT marker genes and to induce COX-2. These effects might contribute to the increased risk for the development of thrombosis and multiple malignancies in obesity.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01581801
2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)
Peer reviewe
Wytyczne ESC dotyczÄ ce diagnostyki i postÄpowania w ostrej zatorowoĆci pĆucnej przygotowane we wspĂłĆpracy z European Respiratory Society (2019). Dane uzupeĆniajÄ ce
Understanding and Preventing Placenta-Mediated Pregnancy Complications
Placenta-mediated pregnancy complications are clinically important conditions and include preeclampsia, placental abruption, intrauterine growth restriction, and late fetal loss. Pathophysiology is complex, and may be linked to prothrombotic disorders such as antiphospholipid syndrome, whose understanding is still evolving. In this narrative review, we will present the latest evidence to better understand hemostatic mechanisms of preeclampsia, as well as in women with placenta-mediated pregnancy complications and inherited thrombophilia or antiphospholipid antibodies. Using four clinical scenarios, the mixed results of preventive efforts through the use of antithrombotic drugs (aspirin, heparin) will be discussed. We will also review knowledge gaps and ongoing research
A Protocol for Improved Precision and Increased Confidence in Nanoparticle Tracking Analysis Concentration Measurements between 50 and 120ânm in Biological Fluids
Nanoparticle tracking analysis (NTA) can be used to quantitate extracellular vesicles (EVs) in biological samples and is widely considered a useful diagnostic tool to detect disease. However, accurately profiling EVs can be challenging due to their small size and heterogeneity. Here, we aimed to provide a protocol to facilitate high-precision particle quantitation by NTA in plasma, the supernatant of activated purified platelets [the platelet releasate (PR)] and in serum, to increase confidence in NTA particle enumeration. The overall variance and the precision of NTA measurements were quantified by root mean square error and relative standard error. Using a bootstrapping approach, we found that increasing video replicates from 5âsâĂâ60âs to 25âsâĂâ60âs captures led to a reduction in overall variance and a reproducible increase in the precision of NTA particle-concentration quantitation for all three biofluids. We then validated our approach in an extended cohort of 32 healthy donors. Our results indicate that for vesicles sized between 50 and 120ânm, the precision of routine NTA measurements in serum, plasma, and PR can be significantly improved by increasing the number of video replicates captured. Our protocol provides a common platform to statistical compare particle size distribution profiles in the exosomal-vesicle size range across a variety of biofluids and in both healthy donor and patient groups
Preventing postpartum venous thromboembolism: A call to action to reduce undue maternal morbidity and mortality
Postpartum venous thromboembolism (VTE) is a leading cause of maternal mortality in developed countries and can carry significant long-term morbidity. Despite being able to identify postpartum VTE risk factors in a large proportion of the obstetrical population, there is little high-quality evidence available to guide practice on who should receive postpartum thromboprophylaxis. Based on epidemiological data, women with a prior history of VTE or known potent thrombophilia are likely to benefit from an extended duration of low-molecular-weight heparin (LMWH) prophylaxis. However, significant controversy exists around the benefit and harm of postpartum thromboprophylaxis in women with more modest risk factors, such as those with mild thrombophilias or transient situational risk factors around labor and delivery, such as cesarean delivery. We review the available data for postpartum VTE risk factors and thromboprophylaxis in these patients. This review highlights the latest evidence in the area of postpartum VTE prevention, and is a call to action for further research in this area to improve maternal morbidity and mortality
S1 Data -
Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.</div