Subscribe to RSS
Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver DiseaseFunding None.
Introduction Hemorrhage and venous thromboembolism (VTE) are recognized complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients are uncertain.
Patients and Methods We studied a retrospective cohort of patients with CLD nonelectively admitted to a specialist intensive care unit (ICU) determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48 hours; later, diagnosed >48 hours post-ICU admission). Associations with baseline clinical and laboratory characteristics, multiorgan failure (MOF), blood product administration, and mortality were explored. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression.
Results Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: early VTE in 80 (13%) and involving the portal vein in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular carcinoma (HCC) and nonalcoholic liver disease were independently associated with early VTE (OR: 2.79, 95% CI: 1.5–5.2 and OR: 2.32, 95% CI: 1.4–3.9, respectively), and HCC, sepsis, and cryoprecipitate use with late VTE (OR: 2.45, 95% CI: 1.11–5.43; OR: 2.26, 95% CI: 1.2–4.3; and OR: 2.60, 95% CI: 1.3–5.1).
Conclusion VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD.
W.B. conceived and supervised the study and design, data analysis and interpretation, and critical review of the paper. T.-W.O. led data collection, interpretation, and writing of the manuscript. L.N.R. contributed to study design, data interpretation, and writing of the manuscript. E.F., L.R., S.N., and B.v.d.B. collected data. V.C.P., B.H., and M.M. interpreted the data and critically reviewed the manuscript. All authors revised and approved the final submission.
* Co-joint senior authors.
Received: 17 March 2021
Accepted: 10 October 2021
Accepted Manuscript online:
12 October 2021
Article published online:
28 December 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44 (01) 217-231
- 2 Arroyo V, Moreau R, Jalan R. Acute-on-chronic liver failure. N Engl J Med 2020; 382 (22) 2137-2145
- 3 Arroyo V, Moreau R, Jalan R, Ginès P. EASL-CLIF Consortium CANONIC Study. Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis. J Hepatol 2015; 62 (1, Suppl): S131-S143
- 4 Jalan R, Saliba F, Pavesi M. et al; CANONIC study investigators of the EASL-CLIF Consortium. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014; 61 (05) 1038-1047
- 5 Fisher C, Patel VC, Stoy SH. et al. Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure. J Crit Care 2018; 43: 54-60
- 6 Zanetto A, Rinder HM, Campello E. et al. Acute kidney injury in decompensated cirrhosis is associated with both hypo- and hyper-coagulable features. Hepatology 2020; 72 (04) 1327-1340
- 7 Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116 (06) 878-885
- 8 Basili S, Raparelli V, Napoleone L. et al; PRO-LIVER Collaborators. Platelet count does not predict bleeding in cirrhotic patients: results from the PRO-LIVER study. Am J Gastroenterol 2018; 113 (03) 368-375
- 9 Shah NL, Northup PG, Caldwell SH. A clinical survey of bleeding, thrombosis, and blood product use in decompensated cirrhosis patients. Ann Hepatol 2012; 11 (05) 686-690
- 10 Montenovo M, Rahnemai-Azar A, Reyes J, Perkins J. Clinical impact and risk factors for portal vein thrombosis for patients on wait list for liver transplant. Exp Clin Transplant 2018; 16 (02) 166-171
- 11 Gulley D, Teal E, Suvannasankha A, Chalasani N, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci 2008; 53 (11) 3012-3017
- 12 Dabbagh O, Oza A, Prakash S, Sunna R, Saettele TM. Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest 2010; 137 (05) 1145-1149
- 13 Blasi A, Patel VC, Adelmeijer J. et al. Mixed fibrinolytic phenotypes in decompensated cirrhosis and acute-on-chronic liver failure with hypofibrinolysis in those with complications and poor survival. Hepatology 2020; 71 (04) 1381-1390
- 14 Montalto P, Vlachogiannakos J, Cox DJ, Pastacaldi S, Patch D, Burroughs AK. Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study. J Hepatol 2002; 37 (04) 463-470
- 15 Roberts LN, Bernal W. Incidence of bleeding and thrombosis in patients with liver disease. Semin Thromb Hemost 2020; 46 (06) 656-664
- 16 Drolz A, Horvatits T, Roedl K. et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology 2016; 64 (02) 556-568
- 17 Moreau R, Jalan R, Gines P. et al; CANONIC Study Investigators of the EASL–CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144 (07) 1426-1437
- 18 Jalan R, Pavesi M, Saliba F. et al; CANONIC Study Investigators; EASL-CLIF Consortium. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015; 62 (04) 831-840
- 19 Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W. 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 surgical patients. J Thromb Haemost 2010; 8 (01) 202-204
- 20 Roberts LN, Porter G, Barker RD. et al. Comprehensive VTE prevention program incorporating mandatory risk assessment reduces the incidence of hospital-associated thrombosis. Chest 2013; 144 (04) 1276-1281
- 21 Intagliata NM, Henry ZH, Shah N, Lisman T, Caldwell SH, Northup PG. Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding. Liver Int 2014; 34 (01) 26-32
- 22 Desborough MJ, Hockley B, Sekhar M, Burroughs AK, Stanworth SJ, Jairath V. National Audit Collaborative. Patterns of blood component use in cirrhosis: a nationwide study. Liver Int 2016; 36 (04) 522-529
- 23 Patel IJ, Rahim S, Davidson JC. et al. Society of Interventional Radiology Consensus Guidelines for the periprocedural management of thrombotic and bleeding risk in patients undergoing percutaneous image-guided interventions-part ii: recommendations: endorsed by the Canadian Association for Interventional Radiology and the Cardiovascular and Interventional Radiological Society of Europe. J Vasc Interv Radiol 2019; 30 (08) 1168.e1-1184.e1
- 24 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
- 25 Vuyyuru SK, Singh AD, Gamanagatti SR, Rout G, Shalimar GD. A randomized control trial of thromboelastography-guided transfusion in cirrhosis for high-risk invasive liver-related procedures. Dig Dis Sci 2020; 65 (07) 2104-2111
- 26 O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA clinical practice update: coagulation in cirrhosis. Gastroenterology 2019; 157 (01) 34.e1-43.e1
- 27 Villanueva C, Colomo A, Bosch A. et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368 (01) 11-21
- 28 Jairath V, Harrison P, Stanworth S. et al. Thrombin generation is normal in cirrhotics with acute variceal haemorrhage: results from a prospective study. Gut 2012; 61 (Suppl. 02) A418-A418
- 29 Cook D, Meade M, Guyatt G. et al; PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011; 364 (14) 1305-1314
- 30 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
- 31 Bezinover D, Iskandarani K, Chinchilli V. et al. Autoimmune conditions are associated with perioperative thrombotic complications in liver transplant recipients: a UNOS database analysis. BMC Anesthesiol 2016; 16 (01) 26
- 32 Kaplan D, Casper TC, Elliott CG. et al. VTE incidence and risk factors in patients with severe sepsis and septic shock. Chest 2015; 148 (05) 1224-1230
- 33 Reynolds PM, Van Matre ET, Wright GC. et al; Colorado Pulmonary Outcomes Research Group (CPOR). Evaluation of prophylactic heparin dosage strategies and risk factors for venous thromboembolism in the critically ill patient. Pharmacotherapy 2019; 39 (03) 232-241
- 34 Zocco MA, Di Stasio E, De Cristofaro R. et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol 2009; 51 (04) 682-689
- 35 Abdel-Razik A, Mousa N, Elhelaly R, Tawfik A. De-novo portal vein thrombosis in liver cirrhosis: risk factors and correlation with the Model for End-stage Liver Disease scoring system. Eur J Gastroenterol Hepatol 2015; 27 (05) 585-592
- 36 Stine JG, Shah PM, Cornella SL. et al. Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis. World J Hepatol 2015; 7 (27) 2774-2780
- 37 Violi F, Corazza GR, Caldwell SH. et al; PRO-LIVER Collaborative Group. Incidence and recurrence of portal vein thrombosis in cirrhotic patients. Thromb Haemost 2019; 119 (03) 496-499
- 38 Emuakhagbon V, Philips P, Agopian V, Kaldas FM, Jones CM. Incidence and risk factors for deep venous thrombosis and pulmonary embolus after liver transplantation. Am J Surg 2016; 211 (04) 768-771
- 39 Nguyen-Buckley C, Gao W, Agopian V. et al. Major thromboembolic complications in liver transplantation: the role of rotational thromboelastometry and cryoprecipitate transfusion. Transplantation 2021; 105 (08) 1771-1777
- 40 Jairath V, Rehal S, Logan R. et al. Acute variceal haemorrhage in the United Kingdom: patient characteristics, management and outcomes in a nationwide audit. Dig Liver Dis 2014; 46 (05) 419-426
- 41 Budnick IM, Davis JPE, Sundararaghavan A. et al. Transfusion with cryoprecipitate for very low fibrinogen levels does not affect bleeding or survival in critically ill cirrhosis patients. Thromb Haemost 2021; 121 (10) 1317-1325