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.

King's College Hospital hosts a busy anticoagulation clinic in south London within the epicentre of the COVID-19 outbreak in the UK [1]. After the UK entered a period of 'lockdown' from 23/03/2020, the Government advised shielding of elderly and vulnerable patients and limiting hospital visits. UK guidance for anticoagulation services was issued (Guidance for the safe switching of warfarin to direct oral anticoagulants (DOACs) for patients with non-valvular AF and venous thromboembolism (DVT / PE) during the coronavirus pandemic) with recommendations around maintaining safe anticoagulation whilst minimising exposure to COVID-19 infection [2]. These included switching to direct oral anticoagulants (DOACs) where appropriate, self-testing INRs, increasing the INR test interval for previously stable patients, and temporarily suspending anticoagulation with VKA therapy where this could no longer be safely continued. Despite implementation of these recommendations, we noted frequent high INR readings in clinical practice during this period. Routine practice at our institution is to perform root cause analysis on all INR results above > 8.0. We report on the frequency of supra-therapeutic INR values during the COVID-19 pandemic compared to the previous year and during lockdown and describe the findings of the root cause analysis. Methods

Pregnancy increases the risk of VTE by 4-to 5-fold, spanning all three trimesters and peaking during the postpartum period. VTE complicates 1-2 per 1000 pregnancies (Heit, 2005) and remains the leading direct cause of maternal death at 1Á13 per 100 000 pregnancies [95% confidence interval (CI) 0Á74-1Á65], accounting for 12Á9% of maternal deaths in the UK between (Knight et al, 2017. Risk factors and prevention of pregnancy-associated VTE have been previously reviewed in detail by Guimicheva et al (2015), and are not further discussed here.