Thrombosis research最新文献

The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bβ, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric “dimer of trimers” (AαBβγ)₂. Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein. Fibrinogen is one of the most prevalent coagulation proteins in blood, and its expression is induced by inflammatory cytokines, wherein circulating fibrinogen levels may increase up to 3-fold during acute inflammatory events. Abnormal levels of circulating fibrinogen are associated with bleeding and thrombotic disorders, as well as several inflammatory diseases. Notably, therapeutic strategies to modulate fibrinogen levels have shown promise in experimental models of disease. Herein, we review pathways mediating fibrinogen synthesis, from gene expression to secretion. Knowledge of these mechanisms may lead to the identification of biomarkers and new therapeutic targets to modulate fibrinogen in health and disease.

Background

Pulmonary embolism may have both physical and psychological consequences for the affected person. Guidelines recommend structured follow-up care, yet this is still not widely practised. Therefore, a national research project was initiated in Denmark in 2021, with the aim of developing, testing, implementing, and evaluating a structured post-pulmonary embolism follow-up care model, ‘Attend-PE’. The objective of this feasibility study was to examine the fidelity, acceptability, and appropriateness of the Attend-PE model in a Danish hospital setting.

Methods

This feasibility study was conducted in two Danish hospitals, using a prospective study design with six months' follow-up. The fidelity, acceptability, and appropriateness of the Attend-PE model's components were evaluated using surveys, registrations sheets, and interviews with two physicians, three nurses, and 29 patients. Qualitative data were analysed using a deductive content analysis, while quantitative data were analysed using descriptive statistics.

Results

Fidelity with the Attend-PE model was good, with a high participation rate of patients in all components of the model. Acceptability was likewise good, as both patients and health care professionals expressed a high level of satisfaction with the model. The health care professionals considered the model to be relevant and suitable in a Danish hospital setting, confirming appropriateness of the model.

Conclusion

This study showed that the Attend-PE model for patients with pulmonary embolism is feasible and acceptable in a Danish hospital setting.

In this review, we embark on a comprehensive exploration of venous thromboembolism (VTE) in the context of medical history and its current practice within medicine. We delve into the landscape of artificial intelligence (AI), exploring its present utility and envisioning its transformative roles within VTE management, from prevention to screening and beyond. Central to our discourse is a forward-looking perspective on the integration of AI within VTE in medicine, advocating for rigorous study design, robust validation processes, and meticulous statistical analysis to gauge the efficacy of AI applications. We further illuminate the potential of large language models and generative AI in revolutionizing VTE care, while acknowledging their inherent limitations and proposing innovative solutions to overcome challenges related to data availability and integrity, including the strategic use of synthetic data. The critical importance of navigating ethical, legal, and privacy concerns associated with AI is underscored, alongside the imperative for comprehensive governance and policy frameworks to regulate its deployment in VTE treatment. We conclude on a note of cautious optimism, where we highlight the significance of proactively addressing the myriad challenges that accompany the advent of AI in healthcare. Through diligent design, stringent validation, extensive education, and prudent regulation, we can harness AI's potential to significantly enhance our understanding and management of VTE. As we stand on the cusp of a new era, our commitment to these principles will be instrumental in ensuring that the promise of AI is fully realized within the realm of VTE care.

Background

Individuals with kidney failure have a compromised haemostatic system making them susceptible to both thrombosis and bleeding.

Objectives

Assessment of primary haemostasis in patients treated with either haemodialysis (HD) or haemodiafiltration (HDF) was performed through the measurement of several coagulation-based tests, both pre- and post-dialysis.

Patients/methods

41 renal failure patients and 40 controls were recruited. Platelet aggregometry, Factor XIII (FXIII), Fibrinogen, Von Willebrand Factor (VWF) and Soluble P-Selectin (sP-Sel) levels were measured.

Results

Maximum platelet aggregation was diminished in renal patients irrespective of aspirin intake. Post-dialysis, platelet function was exacerbated. Pre-dialysis FXIII levels were similar to the healthy cohort and became elevated post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. Fibrinogen levels were already elevated pre-dialysis and further increased post-dialysis. This elevation was associated with the relative decrease of water by dialysis. VWF levels in males were similar to the healthy cohort and became elevated post-dialysis. This elevation was associated with dialysis-related water loss. VWF antigen and activity in female patients were already elevated pre-dialysis and further increased post-dialysis with the exception of VWF activity in HDF treated female patients. sP-Sel levels were lower than those of the healthy cohort and became similar to the healthy cohort post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis.

Conclusions

Whilst platelet aggregometry was diminished, we noted elevated clotting factors such as fibrinogen, FXIII and VWF with no significant differences between HD and HDF-treated patients.

Background

Clinical evidence surrounding edoxaban use in patients weighing <50 kg and >120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients >120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) >95 ml/min, a finding of the ENGAGE AF-TIMI 48 trial when edoxaban was compared to warfarin.

Objective

To derive a population pharmacokinetic (PopPK) model using clinical practice data, to understand the impact of bodyweight and renal function on edoxaban pharmacokinetics.

Method

Edoxaban plasma concentrations and patient characteristics were collated from King's College Hospital anticoagulation clinics between 11/2016 and 08/2022. A PopPK model was developed using non-linear mixed effects modelling and used to simulate edoxaban concentrations at the extremes of bodyweight and with varying renal function.

Results

Data from 409 patients (46 < 50 kg, 34 > 120 kg and 123 with a CrCl > 95 ml/min) provided 455 edoxaban plasma concentrations. A one-compartment model with between-subject variability on clearance with a proportional error model best described the data. The most significant covariates impacting on edoxaban exposure were CrCl and bodyweight. Our work suggests that edoxaban exposure in patients weighing up to 140 kg is comparable to those weighing 75 kg. Edoxaban exposure is reduced in patients weighing <50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl > 95 ml/min compared to CrCl 80 ml/min.

Conclusions

Our population PK model for edoxaban suggests that renal function is a key driver for overall edoxaban exposure. Further clinical outcome data is required to understand clinical effectiveness and adverse outcomes.

Background

Pediatric antiphospholipid syndrome (APS) is one of the most common acquired hypercoagulable states in children, yet it remains poorly characterized.

Objectives

To perform a systematic review and meta-analysis of the pooled incidence of thrombotic recurrence in this population (primary outcome), exploring the effect of age, APS type (primary vs. secondary to autoimmune diseases), and type of index thrombotic event. Secondary outcomes included the incidence of bleeding events and mortality.

Materials and methods

The MEDLINE, EMBASE, and COCHRANE databases were searched for studies reporting outcomes of cohorts of children aged ≤18 years with thrombotic APS as defined by the revised Sydney classification criteria.

Results

A total of 1011 studies were identified; of those, 9 were included in the final analysis (352 patients). The pooled incidence proportion of thrombosis recurrence was 0.27 [0.18–0.37], with an overall follow-up duration of a median of 2.7 to 5.8 years or a mean of 2.6 to 6.1 years. The estimate did not change meaningfully according to APS type (0.30 [0.18–0.46] for primary APS vs. 0.29 [0.19–0.42] for autoimmune APS), nor when the index thrombotic event was venous vs. arterial (0.30 [0.20–0.41] vs. 0.27 [0.27–0.51], respectively). The incidence of bleeding events was not reported in these studies. The incidence proportion of mortality was estimated at 0.07 [0.04–0.11] over the follow-up period, with 8/10 of the reported deaths directly associated with recurrent thrombotic events.

Conclusions

The incidence of thrombotic recurrence in children with APS is high and requires attention to evaluate anticoagulation management in this population.