Coagulation testing and management in liver disease patients.
Stotts MJ; Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA.
Current opinion in gastroenterology [Curr Opin Gastroenterol] 2020 May; Vol. 36 (3), pp. 169-176.
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Publication: : Philadelphia, PA : Lippincott Williams & Wilkins
Original Publication: London ; New York : Gower Academic Journals, [1985-
Ambrosino P, Tarantino L, Di Minno G, et al. The risk of venous thromboembolism in patients with cirrhosis. A systematic review and meta-analysis. Thromb Haemost 2017; 117:139–148.
Boks AL, Brommer EJ, Schalm SW, et al. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage. Hepatology 1986; 6:79–86.
de Boer MT, Molenaar IQ, Hendriks HG, et al. Minimizing blood loss in liver transplantation: progress through research and evolution of techniques. Dig Surg 2005; 22:265–275.
Garcia-Tsao G, Bosch J. Varices and variceal hemorrhage in cirrhosis: a new view of an old problem. Clin Gastroenterol Hepatol 2015; 13:2109–2117.
Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005; 45:1413–1425.
Søgaard KK, Horváth-Puhó E, Grønbaek H, et al. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009; 104:96–101.
Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013; 11:1064–1074.
Tripodi A, Primignani M, Mannucci PM. Abnormalities of hemostasis and bleeding in chronic liver disease: the paradigm is challenged. Intern Emerg Med 2010; 5:7–12.
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.
Bennani-Baiti N, Daw HA. Primary hyperfibrinolysis in liver disease: a critical review. Clin Adv Hematol Oncol 2011; 9:250–252.
Ferro D, Celestini A, Violi F. Hyperfibrinolysis in liver disease. Clin Liver Dis 2009; 13:21–31.
Kujovich JL. Hemostatic defects in end stage liver disease. Crit Care Clin 2005; 21:563–587.
Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981; 26:388–393.
Aseni P, Frangi M, Beati C, et al. Is thrombocytopenia in liver failure dependent on an inadequate synthesis of thrombopoietic stimulating factor by the liver? Med Hypotheses 1988; 26:217–219.
Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of ‘hypersplenic’ thrombocytopenia. J Clin Invest 1966; 45:645–657.
O’Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA clinical practice update: coagulation in cirrhosis. Gastroenterology 2019; 157:34–43.e1.
Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44:440–445.
Costa M, Dalmau A, Sabate A, et al. Low plasma fibrinogen levels and blood product transfusion in liver transplantation. Minerva Anestesiol 2014; 80:568–573.
Sabate A, Gutierrez R, Beltran J, et al. Impact of preemptive fibrinogen concentrate on transfusion requirements in liver transplantation: a multicenter, randomized, double-blind, placebo-controlled trial. Am J Transplant 2016; 16:2421–2429.
Davis JPE, Northup PG, Caldwell SH, Intagliata NM. Viscoelastic testing in liver disease. Ann Hepatol 2018; 17:205–213.
Jeong SM, Song JG, Seo H, et al. Quantification of both platelet count and fibrinogen concentration using maximal clot firmness of thromboelastometry during liver transplantation. Transplant Proc 2015; 47:1890–1895.
Papatheodoridis GV, Patch D, Webster GJ, et al. Infection and hemostasis in decompensated cirrhosis: a prospective study using thrombelastography. Hepatology 1999; 29:1085–1090.
Stravitz RT, Lisman T, Luketic VA, et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012; 56:129–136.
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; 63:566–573.
Trzebicki J, et al. The use of thromboelastometry in the assessment of hemostasis during orthotopic liver transplantation reduces the demand for blood products. Ann Transplant 2010; 15:19–24.
Wang SC, Shieh JF, Chang KY, et al. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc 2010; 42:2590–2593.
Lisman T, van Leeuwen Y, Adelmeijer J, et al. Interlaboratory variability in assessment of the model of end-stage liver disease score. Liver Int 2008; 28:1344–1351.
Trotter JF, Olson J, Lefkowitz J, et al. Changes in international normalized ratio (INR) and model for end-stage liver disease (MELD) based on selection of clinical laboratory. Am J Transplant 2007; 7:1624–1628.
Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995; 36:437–441.
Bruzzi JF, O’Connell MJ, Thakore H, et al. Transjugular liver biopsy: assessment of safety and efficacy of the Quick-Core biopsy needle. Abdom Imaging 2002; 27:711–715.
Grabau CM, Crago SF, Hoff LK, et al. Performance standards for therapeutic abdominal paracentesis. Hepatology 2004; 40:484–488.
Baltz JG, Argo CK, Al-Osaimi AM, et al. Mortality after percutaneous endoscopic gastrostomy in patients with cirrhosis: a case series. Gastrointest Endosc 2010; 72:1072–1075.
Youssef WI, Salazar F, Dasarathy S, et al. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol 2003; 98:1391–1394.
Intagliata NM, Argo CK, Stine JG, et al. Concepts and controversies in haemostasis and thrombosis associated with liver disease: proceedings of the 7th international coagulation in liver disease conference. Thromb Haemost 2018; 118:1491–1506.
Runyon BA. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis. Hepatology 2013; 57:1651–1653.
Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2017; 65:310–335.
Hibbert RM, Atwell TD, Lekah A, et al. Safety of ultrasound-guided thoracentesis in patients with abnormal preprocedural coagulation parameters. Chest 2013; 144:456–463.
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; 155:705–718.
Kim ES. Lusutrombopag: first global approval. Drugs 2016; 76:155–158.
Shah NL, Intagliata NM, Northup PG, et al. Procoagulant therapeutics in liver disease: a critique and clinical rationale. Nat Rev Gastroenterol Hepatol 2014; 11:675–682.
Rai R, Nagral S, Nagral A. Surgery in a patient with liver disease. J Clin Exp Hepatol 2012; 2:238–246.
Stellingwerff M, Brandsma A, Lisman T, Porte RJ. Prohemostatic interventions in liver surgery. Semin Thromb Hemost 2012; 38:244–249.
Ng VL. Liver disease, coagulation testing, and hemostasis. Clin Lab Med 2009; 29:265–282.
Kor DJ, Stubbs JR, Gajic O. Perioperative coagulation management--fresh frozen plasma. Best Pract Res Clin Anaesthesiol 2010; 24:51–64.
Vieira da Rocha EC, D’Amico EA, Caldwell SH, et al. A prospective study of conventional and expanded coagulation indices in predicting ulcer bleeding after variceal band ligation. Clin Gastroenterol Hepatol 2009; 7:988–993.
Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46:922–938.
Qureshi W, Adler DG, Davila R, et al. ASGE Guideline: the role of endoscopy in the management of variceal hemorrhage, updated July. Gastrointest Endosc 2005; 62:651–655.
de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53:762–768.
Villanueva C, Colomo A, Bosch A. Transfusion for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368:1362–1363.
Kravetz D, Sikuler E, Groszmann RJ. Splanchnic and systemic hemodynamics in portal hypertensive rats during hemorrhage and blood volume restitution. Gastroenterology 1986; 90 (5 Pt 1):1232–1240.
Castaneda B, Morales J, Lionetti R, et al. Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats. Hepatology 2001; 33:821–825.
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; 71:235–246.
European Association for the Study of the Liver. Electronic address: . EASL Clinical Practice Guidelines: vascular diseases of the liver. J Hepatol 2016; 64:179–202.
de Franchis R. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63:743–752.
DeLeve LD, Valla DC, Garcia-Tsao G. Vascular disorders of the liver. Hepatology 2009; 49:1729–1764.
Chokesuwattanaskul R, Thongprayoon C, Bathini T, et al. Epidemiology of atrial fibrillation in patients with cirrhosis and clinical significance: a meta-analysis. Eur J Gastroenterol Hepatol 2019; 31:514–519.
Villa E, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143:1253–1260.e4.
Potze W, Arshad F, Adelmeijer J, et al. Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis. Br J Haematol 2013; 163:666–673.
Intagliata NM, Henry ZH, Maitland H, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci 2016; 61:1721–1727.
Kunk PR, Kraaijpoel N, Büller HR, van Es N. Direct oral anticoagulants in patients with cirrhosis appear safe and effective. Blood 2016; 128:.
Hum J, Shatzel JJ, Jou JH, et al. The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis. Eur J Haematol 2017; 98:393–397.
Lisman T, Kleiss S, Patel VC, et al. In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis. Liver Int 2018; 38:1988–1996.
Shami VM, Caldwell SH, Hespenheide EE, et al. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl 2003; 9:138–143.
Shah NL, Northup PG, Caldwell SH. A clinical survey of bleeding, thrombosis, and blood product use in decompensated cirrhosis patients. Ann Hepatol 2012; 11:686–690.
Groeneveld D, Pereyra D, Veldhuis Z, et al. Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans. Blood 2019; 133:1245–1256.
Bitto N, Liguori E, La Mura V. Coagulation, microenvironment and liver fibrosis. Cells 2018; 7: pii: E85. (PMID: e85)
Caldwell SH, Hoffman M, Lisman T, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006; 44:1039–1046.
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Date Created: 20200307 Latest Revision: 20210205
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Purpose of Review: The present article aims to provide clinicians with an overview of coagulation testing in individuals with liver disease, to discuss available procoagulants and the rationale for their use, and to provide management strategies in a variety of common clinical scenarios.
Recent Findings: Clinicians and researchers are gaining an increased understanding of the shortfalls of assessing bleeding risk using traditional tests of coagulation. The use of global tests of clot formation, including viscoelastic testing and thrombin generation analysis, continues to evolve and guide the management of these patients.
Summary: Abnormal coagulation testing in individuals with cirrhosis leads to a variety of difficult clinical scenarios that can be challenging for practitioners. With advanced liver disease, changes in the traditional tests of hemostasis such as the international normalized ratio reflect decreased synthesis of procoagulant factors but do not capture concomitant decreases in anticoagulant factors. In this setting, transfusion thresholds targeting platelet and fibrinogen goals may provide an effective strategy to optimize clot formation. Global tests of clot formation provide practical information to clinicians and can help guide decision making, although optimal target levels have not been validated.