RSS-Feed abonnieren
DOI: 10.1055/s-0040-1714203
Shortcomings in Design and Analysis of Clinical Studies on Bleeding and Thrombosis in Patients with Cirrhosis
Funding None.![](https://www.thieme-connect.de/media/sth/202006/lookinside/thumbnails/10-1055-s-0040-1714203_02747-1.jpg)
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.
Keywords
portal vein thrombosis - esophageal varices - procedural bleeding - anticoagulants - clinical study designPublikationsverlauf
Artikel online veröffentlicht:
05. August 2020
© 2020. Thieme. All rights reserved.
Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.
-
References
- 1 Mehran R, Rao SV, Bhatt DL. , et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
- 2 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
- 3 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
- 4 de Franchis R. Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53 (04) 762-768
- 5 Zampino R, Lebano R, Coppola N. , et al. The use of nonselective beta blockers is a risk factor for portal vein thrombosis in cirrhotic patients. Saudi J Gastroenterol 2018; 24 (01) 25-29
- 6 Stine JG, Shah NL, Argo CK, Pelletier SJ, Caldwell SH, Northup PG. Increased risk of portal vein thrombosis in patients with cirrhosis due to nonalcoholic steatohepatitis. Liver Transpl 2015; 21 (08) 1016-1021
- 7 Violi F, Corazza GR, Caldwell SH. , et al; PRO-LIVER Collaborators. Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry. Intern Emerg Med 2016; 11 (08) 1059-1066
- 8 Villa E, Cammà C, Marietta M. , et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143 (05) 1253-1260.e4
- 9 Nery F, Chevret S, Condat B. , et al; Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 2015; 61 (02) 660-667
- 10 Englesbe MJ, Schaubel DE, Cai S, Guidinger MK, Merion RM. Portal vein thrombosis and liver transplant survival benefit. Liver Transpl 2010; 16 (08) 999-1005
- 11 Berry K, Taylor J, Liou IW, Ioannou GN. Portal vein thrombosis is not associated with increased mortality among patients with cirrhosis. Clin Gastroenterol Hepatol 2015; 13 (03) 585-593
- 12 Yerdel MA, Gunson B, Mirza D. , et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation 2000; 69 (09) 1873-1881
- 13 Sarin SK, Philips CA, Kamath PS. , et al. Toward a comprehensive new classification of portal vein thrombosis in patients with cirrhosis. Gastroenterology 2016; 151 (04) 574-577.e3
- 14 Seeff LB, Everson GT, Morgan TR. , et al; HALT–C Trial Group. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol 2010; 8 (10) 877-883
- 15 Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther 2005; 21 (05) 525-529
- 16 Sarin SK, Wadhawan M, Gupta R, Shahi H. Evaluation of endoscopic variceal ligation (EVL) versus propanolol plus isosorbide mononitrate/nadolol (ISMN) in the prevention of variceal rebleeding: comparison of cirrhotic and noncirrhotic patients. Dig Dis Sci 2005; 50 (08) 1538-1547
- 17 De Pietri L, Bianchini M, Montalti R. , et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial. Hepatology 2016; 63 (02) 566-573
- 18 Terrault N, Chen YC, Izumi N. , et al. Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia. Gastroenterology 2018; 155 (03) 705-718
- 19 Afdhal NH, Giannini EG, Tayyab G. , et al; ELEVATE Study Group. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 2012; 367 (08) 716-724
- 20 Peck-Radosavljevic M, Simon K, Iacobellis A. , et al. Lusutrombopag for the treatment of thrombocytopenia in patients with chronic liver disease undergoing invasive procedures (L-PLUS 2). Hepatology 2019; 70 (04) 1336-1348
- 21 Vuyyuru SK, Singh AD, Gamanagatti SR, Rout G, Gunjan D. , Shalimar. A randomized control trial of thromboelastography-guided transfusion in cirrhosis for high-risk invasive liver-related procedures. Dig Dis Sci 2019
- 22 Runyon BA, Committee APG. AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology 2009; 49 (06) 2087-2107
- 23 Kumar M, Ahmad J, Maiwall R. , et al. Thromboelastography-guided blood component use in patients with cirrhosis with nonvariceal bleeding: a randomized controlled trial. Hepatology 2020; 71 (01) 235-246
- 24 Rout G, Gunjan D. , et al. Thromboelastography-guided blood product transfusion in cirrhosis patients with variceal bleeding: a randomized controlled trial. J Clin Gastroenterol 2020; 54 (03) 255-262
- 25 Englesbe MJ, Kubus J, Muhammad W. , et al. Portal vein thrombosis and survival in patients with cirrhosis. Liver Transpl 2010; 16 (01) 83-90