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.
Background
Emerging safety and efficacy data for rivaroxaban suggest traditional therapy and rivaroxaban are comparable in the morbidly obese. However, real‐world data that indicate pharmacokinetic (PK) parameters are comparable at the extremes of body size are lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee (ISTH SSC) suggests avoiding the use of direct oral anticoagulants (DOACs) in patients weighing >120 kg or with a body mass index >40 kg/m2 and gives no recommendation on the use of DOACs in those <50 kg.
Objectives
To generate a population PK model to understand the influence of bodyweight on rivaroxaban exposure from clinical practice data.
Method
Rivaroxaban plasma concentrations and patient characteristics were collated between 2013 and 2018 at King's College Hospital anticoagulation clinic. A population PK model was developed using a nonlinear mixed effects approach and then used to simulate rivaroxaban concentrations at the extremes of bodyweight.
Results
A robust population PK model derived from 913 patients weighing between 39 kg and 172 kg was developed. The model included data from n = 86 >120 kg, n = 74 BMI >40 kg/m2, and n = 30 <50 kg. A one‐compartment model with between‐subject variability on clearance and a proportional error model best described the data. Creatinine clearance calculated by Cockcroft‐Gault, with lean bodyweight as the weight descriptor in this equation, was the most significant covariate influencing rivaroxaban exposure.
Conclusions
Our work demonstrates rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory. We recommend that the ISTH SSC revises the current guidance with respect to rivaroxaban at extremes of body size.
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