CPRD StudyPrimary Care PASS Study

Application of the International Society on Thrombosis and Haemostasis (ISTH) classification of major bleeds within a Post Authorization Safety Study.

Miranda Davies, Vicki Osborne, Deborah Layton and Saad Shakir.


Haemorrhage is a frequent complication of anticoagulant (AC) use. In order to compare incidences between trials a definition of major bleeds (MB) in non surgical studies was developed by the International Society on Thrombosis and Haemostasis (ISTH) in 2005. In recent years, the Committee for Medicinal Products for Human Use (CHMP) has recommended its use in studies for prevention of stroke and systemic embolic events (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 on the 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 and prevention of recurrent DVT and PE [n=1005]. Recruitment Sep2013-2016. Information (info) was obtained on bleeds 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) if none of the MB criteria were met, but if medical attention was required and/or a change in antithrombotic therapy and/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.