Shortcomings in Design and Analysis of Clinical Studies on Bleeding and Thrombosis in Patients with Cirrhosis

Abstract

Significant gains have been made in our understanding of bleeding and thrombosis in patients with liver disease in recent years, with concurrent exponential growth in the scientific literature published in this realm. Clinical studies of this population are challenging for multiple reasons including some hurdles unique to this population. Cirrhosis patients as a whole, especially those with decompensated cirrhosis, are a high-risk and heterogeneous population prone to serious adverse events. Outcomes of bleeding and thrombosis are relatively rare and lack standardized, validated definitions. Standard practices for clinical care have evolved rapidly and rendered some control data uninformative. We aim to highlight these challenges and make recommendations for best practices for future study design and implementation. Multidisciplinary collaboration with proceduralists, careful study design including attention to validated clinically relevant outcomes, and aggressive pursuit of all funding streams will be key to continued scientific success in this burgeoning field.

EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis

“…All recommendations were discussed and approved by all panellists. The strength of the recommendations in these guidelines has been graded according to the OCEBM in 2 categories: strong or weak (2). A glossary has also been provided to standardise terminology and definitions.…”

“…Clinical studies on bleeding and thrombosis in patients with liver disease have been of poor to moderate quality for reasons outlined elsewhere. 2 As an example, the question of how to manage haemostatic abnormalities prior to invasive procedures has not been addressed by adequately powered randomised studies. Ideally, a pragmatic study addressing this issue should include an arm where blood product transfusions are administered on the basis of pre-selected coagulation test cut-offs and a comparison arm where no prophylactic blood product transfusion is mandated, and only rescue treatment is allowed.…”

Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases

“…Further study of viscoelastic testing with standardized clinical bleeding endpoints is needed. ( 24 )…”

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“…Subsequently, Northup and Davis discuss shortcomings in clinical studies on the prevention and management of bleeding and thrombosis and provide recommendations for future studies. 9 The authors stress the importance of clear and validated clinical end points, proper sample sizes, and multicenter and multidisciplinary efforts to take this field forward. Next, Nicoară-Farcău et al discuss new insights into the pathogenesis and management of cirrhotic portal vein thrombosis.…”