Post-discharge venous thromboembolism following hospital admission with COVID-19

The association of severe COVID-19 with an increased risk of VTE has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for post discharge thromboprophylaxis remains controversial and this is reflected in the conflicting recommendations of expert guidelines. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report post-discharge VTE data from an ongoing quality improvement programme incorporating root cause analysis of hospital-associated VTE (HA-VTE). Following 1,877 hospital discharges associated with COVID-19, there were 9 episodes of HA-VTE diagnosed within 42 days, to give a post-discharge rate of 4.8 per 1000 discharges. Over 2019, following 18,159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for post-discharge HA-VTE associated with COVID-19 compared to 2019 was 1.6 (95% CI 0.77-3.1). Hospitalisation with COVID-19 does not appear to increase the risk of post-discharge HA-VTE compared to hospitalisation with other acute medical illness. Given the risk-benefit ratio of post discharge thromboprophylaxis remains uncertain, randomised controlled trials to evaluate the role of continuing thromboprophylaxis in patients with COVID-19 following hospital discharge are required

Can edoxaban be used at extremes of bodyweight and in patients with a creatinine clearance ≥95 ml/min? – A population pharmacokinetic analysis

Background: Clinical evidence surrounding edoxaban use in patients weighing &lt;50 kg and &gt;120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients &gt;120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) &gt;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 &lt; 50 kg, 34 &gt; 120 kg and 123 with a CrCl &gt; 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 &lt;50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl &gt; 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.</p