CPRD StudyPrimary Care PASS Study

Abstract 1003: Application of the International Society on Thrombosis and Haemostasis (ISTH) Definition of Major Bleeds To Bleeding Events Within a Post Authorization Safety Study

Miranda Davies, Vicki Osborne, Deborah Layton, Saad Shakirr


Haemorrhage is a frequent complication of anticoagulant (AC) use. In order to compare incidencesbetween trials a definition of major bleeds (MB) in non surgical studies was developed by the InternationalSociety on Thrombosis and Haemostasis (ISTH) in 2005. In recent years, the Committee for Medicinal Productsfor Human Use (CHMP) has recommended its use in studies for prevention of stroke and systemic embolicevents (SEE) in patients (pts) with non valvular atrial fibrillation (NVAF) and prevention of deep vein thrombosis(DVT) and pulmonary embolus (PE). Bleeds reported in a Specialist Cohort Event Monitoring (SCEM) study onthe oral AC rivaroxaban (conducted as part of Risk Management Plan) will be classified using this definition.


To describe the methodological considerations of applying this definition to observational data.


Aim to collect data on 1700 pts treated for the prevention of SEE [n=561], and the treatment andprevention of recurrent DVT and PE [n=1005]. Recruitment Sep2013-2016. Information (info) was obtained onbleeds that occurred during initial 12 weeks; criteria for MB included: a fall in Hb of ≥ 2 g/dL, a transfusion of ≥2 units, critical organ site, or fatal outcome. Bleeds will be classified as clinically relevant non major (CRNM) ifnone of the MB criteria were met, but if medical attention was required and/or a change in antithrombotic therapyand/or any other bleed with clinical consequences.


To minimise misclassification, supplementary info will be used to validate and confirm the type, obtain missing data and further details of the bleed (site, management, and outcome). All bleeds will be adjudicated by an expert, and interim results will be published.


By systematically applying the ISTH definition, we hope to gain better understanding of the type of bleeds reported in a cohort of AC users, associated risk factors and outcome details. This should enable more meaningful comparisons to be made between major and CRNM bleeding incidences obtained in this setting with those observed during trials.