@article{995e6d5921a248fbb0f463483a5bb590,
title = "Definitions of fatal bleeding in clinical studies evaluating anticoagulant treatment for venous thromboembolism: A scoping review",
abstract = "Background: Fatal bleeding is a component of the primary safety outcome in most studies evaluating anticoagulation for venous thromboembolism (VTE), but a standardized definition for fatal bleeding is lacking. Objectives: To summarize definitions of fatal bleeding and describe the range of case-fatality rates of major bleeding in VTE studies. Methods: MEDLINE, Embase, and CENTRAL databases were searched from January 2008 to July 2021 for prospective studies that enrolled patients with VTE and evaluated the efficacy/safety of anticoagulation for VTE treatment or included fatal or major bleeding as primary outcome. Two authors independently performed study selection and data extraction. The primary outcome was the definition of fatal bleeding. The secondary outcome was the case-fatality rate of major bleeding. Data were analyzed using descriptive statistics. Results: Of 4911 records identified, we included 132 articles representing 89 distinct studies. Twenty-seven (20%) articles and 7 of 89 (8%) studies reported a definition of fatal bleeding. Overall, we identified 3 different types of definitions that were either on the basis of a specific time interval between bleeding and death, bleeding location (intracranial) or clinical presentation (hemodynamic deterioration), or mainly relied on the judgment of the adjudication committee to determine the cause of death. The case-fatality rate of major bleeding ranged from 0 to 60% (median, 9.1%; interquartile range, 2.8%-18%). Conclusion: Less than 10% of studies assessing anticoagulant treatment for VTE reported a definition for fatal bleeding. The lack of a (standardized) definition for fatal bleeding may lead to inaccurate estimates of the risk of fatal bleeding, particularly when compared across studies.",
keywords = "anticoagulation, bleeding, cause of death, outcome assessment, venous thromboembolism",
author = "Carla Schenker and Marx, {Caterina E.} and No{\'e}mie Kraaijpoel and {le Gal}, Gr{\'e}goire and Siegal, {Deborah M.} and Klok, {Frederikus A.} and Drahomir Aujesky and Tobias Tritschler",
note = "Funding Information: G.L.G. received honoraria for lectures from Aspen Pharma, BMS, Leo Pharma, Pfizer, and Sanofi, all outside this work and paid to his institution. F.A.K. has received research grants from Bayer , BMS , BSCI , MSD , LEO Pharma , Actelion , The Netherlands Organization for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation, and the Horizon Europe Program, all outside this work and paid to his institution. The remaining authors state that they have no conflicts of interest. Funding Information: Funding information G.L.G., D.M.S., and T.T. are members of the Canadian Venous Thromboembolism Research Network (CanVECTOR); the Network received grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). G.L.G. holds a mid-career clinician scientist award from the Heart and Stroke Foundation of Ontario and is the Chair of the Diagnosis of Venous Thromboembolism, Department of Medicine, University of Ottawa. D.M.S. holds a Tier 2 Canada Research Chair in Anticoagulant Treatment of Cardiovascular Disease. The funders had no role in the study design, collection, analysis, and interpretation of the data, the writing of the manuscript, and the decision to submit the article for publication.We thank Heidrun Janka, MSc, MA LIS (information specialist at the University of Bern), for reviewing the search strategy. C.S. G.L.G. D.M.S. F.A.K. D.A. and T.T. conceived and designed the study. C.S. C.E.M. and T.T. performed study selection and data extraction. C.S. and T.T. analyzed the data. C.S. and T.T. drafted the manuscript. All authors critically revised the manuscript for important intellectual content and provided final approval of the manuscript. G.L.G. received honoraria for lectures from Aspen Pharma, BMS, Leo Pharma, Pfizer, and Sanofi, all outside this work and paid to his institution. F.A.K. has received research grants from Bayer, BMS, BSCI, MSD, LEO Pharma, Actelion, The Netherlands Organization for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation, and the Horizon Europe Program, all outside this work and paid to his institution. The remaining authors state that they have no conflicts of interest. Funding Information: Funding information G.L.G., D.M.S., and T.T. are members of the Canadian Venous Thromboembolism Research Network (CanVECTOR); the Network received grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). G.L.G. holds a mid-career clinician scientist award from the Heart and Stroke Foundation of Ontario and is the Chair of the Diagnosis of Venous Thromboembolism, Department of Medicine, University of Ottawa. D.M.S. holds a Tier 2 Canada Research Chair in Anticoagulant Treatment of Cardiovascular Disease. The funders had no role in the study design, collection, analysis, and interpretation of the data, the writing of the manuscript, and the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2023 International Society on Thrombosis and Haemostasis",
year = "2023",
month = jun,
doi = "https://doi.org/10.1016/j.jtha.2023.02.013",
language = "English",
volume = "21",
pages = "1553--1566",
journal = "Journal of thrombosis and haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "6",
}