Prevention and Management of Bleeding Risk Related to Invasive Procedures in Cirrhosis

Abstract

Cirrhosis represents the end stage of chronic liver disease and its transition from a compensated to a decompensated status is mainly driven by portal hypertension and systemic inflammation. Although relevant modifications in the evaluation of the coagulative balance in cirrhosis across its natural history have occurred and alterations in routine indices of hemostasis have lost their role as indicators of the hemorrhagic risk of patients with liver cirrhosis, these are still perceived as prone to bleed when admitted to invasive procedures. This view, which is still present in guidelines addressing the management of bleeding risk, makes preprocedural transfusion of plasma and platelets still an ongoing clinical practice. In this review, we describe the limitations of both bleeding risk assessment in cirrhotic patients admitted to radiologic and endoscopic invasive procedures and evaluate whether preventive strategies indicated by current guidelines can affect the procedure-related hemorrhagic events.

Keywords

viscoelastic tests - acute on chronic liver failure - coagulopathy - decompensation

• References

• 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 de Franchis R. ; Baveno VI Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63 (03) 743-752
• 3 Turco L, Garcia-Tsao G, Magnani I. , et al. Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis. J Hepatol 2018; 68 (05) 949-958
• 4 Hernaez R, Solà E, Moreau R, Ginès P. Acute-on-chronic liver failure: an update. Gut 2017; 66 (03) 541-553
• 5 Basili S, Raparelli V, Violi F. The coagulopathy of chronic liver disease: is there a causal relationship with bleeding? Yes. Eur J Intern Med 2010; 21 (02) 62-64
• 6 Liumbruno GM, Bennardello F, Lattanzio A, Piccoli P, Rossetti G. ; Italian Society of Transfusion Medicine and Immunohaematology Working Party. Recommendations for the transfusion management of patients in the peri-operative period. III. The post-operative period. Blood Transfus 2011; 9 (03) 320-335
• 7 Patel IJ, Davidson JC, Nikolic B. , et al; Standards of Practice Committee, with Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Endorsement. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol 2012; 23 (06) 727-736
• 8 Søgaard KK, Horváth-Puhó E, Grønbaek H, Jepsen P, Vilstrup H, Sørensen HT. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009; 104 (01) 96-101
• 9 Andriulli A, Tripodi A, Angeli P. , et al; Under the Auspices of the Italian Association for the Study of Liver Diseases (AISF) and the Italian Society of Internal Medicine (SIMI). Hemostatic balance in patients with liver cirrhosis: report of a consensus conference. Dig Liver Dis 2016; 48 (05) 455-467
• 10 European Association for the Study of the Liver. Electronic address: [e-mail]. Vascular diseases of the liver. J Hepatol 2016; 64 (01) 179-202
• 11 An J, Shim JH, Kim SO. , et al. Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: a registry-based matched case-control study. Circulation 2014; 130 (16) 1353-1362
• 12 Kalaitzakis E, Rosengren A, Skommevik T, Björnsson E. Coronary artery disease in patients with liver cirrhosis. Dig Dis Sci 2010; 55 (02) 467-475
• 13 Kelly DA, Tuddenham EG. Haemostatic problems in liver disease. Gut 1986; 27 (03) 339-349
• 14 Ragni MV, Lewis JH, Spero JA, Hasiba U. Bleeding and coagulation abnormalities in alcoholic cirrhotic liver disease. Alcohol Clin Exp Res 1982; 6 (02) 267-274
• 15 Lisman T, Caldwell SH, Burroughs AK. , et al; Coagulation in Liver Disease Study Group. Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol 2010; 53 (02) 362-371
• 16 Hollestelle MJ, Geertzen HG, Straatsburg IH, van Gulik TM, van Mourik JA. Factor VIII expression in liver disease. Thromb Haemost 2004; 91 (02) 267-275
• 17 Tripodi A, Primignani M, Chantarangkul V. , et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137 (06) 2105-2111
• 18 Dahlbäck B. Progress in the understanding of the protein C anticoagulant pathway. Int J Hematol 2004; 79 (02) 109-116
• 19 Castelino DJ, Salem HH. Natural anticoagulants and the liver. J Gastroenterol Hepatol 1997; 12 (01) 77-83
• 20 Bianchini M, De Pietri L, Villa E. Coagulopathy in liver diseases: complication or therapy?. Dig Dis 2014; 32 (05) 609-614
• 21 Tripodi A, Salerno F, Chantarangkul V. , et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41 (03) 553-558
• 22 Lisman T, Bongers TN, Adelmeijer J. , et al. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 2006; 44 (01) 53-61
• 23 Hugenholtz GC, Adelmeijer J, Meijers JC, Porte RJ, Stravitz RT, Lisman T. An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome. Hepatology 2013; 58 (02) 752-761
• 24 Ferguson JW, Helmy A, Ludlam C, Webb DJ, Hayes PC, Newby DC. Hyperfibrinolysis in alcoholic cirrhosis: relative plasminogen activator inhibitor type 1 deficiency. Thromb Res 2008; 121 (05) 675-680
• 25 Violi F, Basili S, Raparelli V, Chowdary P, Gatt A, Burroughs AK. Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?. J Hepatol 2011; 55 (06) 1415-1427
• 26 Leebeek FW, Rijken DC. The fibrinolytic status in liver diseases. Semin Thromb Hemost 2015; 41 (05) 474-480
• 27 Simon K, Orłowska I, Pazgan-Simon M. The risk of complications of endoscopic procedures in patients with liver cirrhosis. Clin Exp Hepatol 2017; 3 (03) 135-140
• 28 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
• 29 Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116 (06) 878-885
• 30 Tripodi A, Primignani M, Mannucci PM, Caldwell SH. Changing concepts of cirrhotic coagulopathy. Am J Gastroenterol 2017; 112 (02) 274-281
• 31 Giannini EG, Greco A, Marenco S, Andorno E, Valente U, Savarino V. Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease. Clin Gastroenterol Hepatol 2010; 8 (10) 899-902 , quiz e109
• 32 Basili S, Raparelli V, Napoleone L. , et al. Platelet count does not predict bleeding in cirrhotic patients: results from the PRO-LIVER study. Am J Gastroenterol 2018; 113 (03) 368-375
• 33 Krishna SG, Rao BB, Thirumurthi S. , et al. Safety of endoscopic interventions in patients with thrombocytopenia. Gastrointest Endosc 2014; 80 (03) 425-434
• 34 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
• 35 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
• 36 DeAngelis GA, Khot R, Haskal ZJ. , et al. Bleeding risk and management in interventional procedures in chronic liver disease. J Vasc Interv Radiol 2016; 27 (11) 1665-1674
• 37 de Maat MP, Nieuwenhuizen W, Knot EA, van Buuren HR, Swart GR. Measuring plasma fibrinogen levels in patients with liver cirrhosis. The occurrence of proteolytic fibrin(ogen) degradation products and their influence on several fibrinogen assays. Thromb Res 1995; 78 (04) 353-362
• 38 Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014; 54 (05) 1389-1405 , quiz 1388
• 39 Nadim MK, Durand F, Kellum JA. , et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol 2016; 64 (03) 717-735
• 40 Hugenholtz GC, Macrae F, Adelmeijer J. , et al. Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen. J Thromb Haemost 2016; 14 (05) 1054-1066
• 41 Lancé MD. A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis. Thromb J 2015; 13: 1-6
• 42 Ruberto MF, Sorbello O, Civolani A, Barcellona D, Demelia L, Marongiu F. Clot wave analysis and thromboembolic score in liver cirrhosis: two opposing phenomena. Int J Lab Hematol 2017; 39 (04) 369-374
• 43 Castoldi E, Rosing J. Thrombin generation tests. Thromb Res 2011; 127 (Suppl. 03) S21-S25
• 44 Rijken DC, Kock EL, Guimarães AH. , et al. Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests. J Thromb Haemost 2012; 10 (10) 2116-2122
• 45 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
• 46 De Pietri L, Bianchini M, Rompianesi G, Bertellini E, Begliomini B. Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation. World J Transplant 2016; 6 (03) 583-593
• 47 Segal JB, Dzik WH. ; Transfusion Medicine/Hemostasis Clinical Trials Network. 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 (09) 1413-1425
• 48 Hall DP, Estcourt LJ, Doree C, Hopewell S, Trivella M, Walsh TS. Plasma transfusions prior to insertion of central lines for people with abnormal coagulation. Cochrane Database Syst Rev 2016; 9: CD011756
• 49 D'Amico G, Pasta L, Morabito A. , et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther 2014; 39 (10) 1180-1193
• 50 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 , 1437.e1–1437.e9
• 51 Jalan R, Gines P, Olson JC. , et al. Acute-on chronic liver failure. J Hepatol 2012; 57 (06) 1336-1348
• 52 Gustot T, Fernandez J, Garcia E. , et al; CANONIC Study Investigators of the EASL-CLIF Consortium. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 2015; 62 (01) 243-252
• 53 Clària J, Stauber RE, Coenraad MJ. , et al; CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF). Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure. Hepatology 2016; 64 (04) 1249-1264
• 54 Bernal W, Jalan R, Quaglia A, Simpson K, Wendon J, Burroughs A. Acute-on-chronic liver failure. Lancet 2015; 386 (10003): 1576-1587
• 55 Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. ; American Association for the Study of Liver Diseases. Liver biopsy. Hepatology 2009; 49 (03) 1017-1044
• 56 Takyar V, Etzion O, Heller T. , et al. Complications of percutaneous liver biopsy with Klatskin needles: a 36-year single-centre experience. Aliment Pharmacol Ther 2017; 45 (05) 744-753
• 57 Sawyerr AM, McCormick PA, Tennyson GS. , et al. A comparison of transjugular and plugged-percutaneous liver biopsy in patients with impaired coagulation. J Hepatol 1993; 17 (01) 81-85
• 58 Kalambokis G, Manousou P, Vibhakorn S. , et al. Transjugular liver biopsy--indications, adequacy, quality of specimens, and complications--a systematic review. J Hepatol 2007; 47 (02) 284-294
• 59 Dohan A, Guerrache Y, Dautry R. , et al. Major complications due to transjugular liver biopsy: incidence, management and outcome. Diagn Interv Imaging 2015; 96 (06) 571-577
• 60 Hari A, Nair HK, De Gottardi A, Baumgartner I, Dufour JF, Berzigotti A. Diagnostic hepatic haemodynamic techniques: safety and radiation exposure. Liver Int 2017; 37 (01) 148-154
• 61 Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther 2005; 21 (05) 525-529
• 62 Sharzehi K, Jain V, Naveed A, Schreibman I. Hemorrhagic complications of paracentesis: a systematic review of the literature. Gastroenterol Res Pract 2014; 2014: 985141
• 63 Hung A, Garcia-Tsao G. Acute kidney injury, but not sepsis, is associated with higher procedure-related bleeding in patients with decompensated cirrhosis. Liver Int 2018; . (epub ahead of print)
• 64 Xiol X, Castellví JM, Guardiola J. , et al. Spontaneous bacterial empyema in cirrhotic patients: a prospective study. Hepatology 1996; 23 (04) 719-723
• 65 Xiol X, Castellote J, Cortes-Beut R, Delgado M, Guardiola J, Sesé E. Usefulness and complications of thoracentesis in cirrhotic patients. Am J Med 2001; 111 (01) 67-69
• 66 Hibbert RM, Atwell TD, Lekah A. , et al. Safety of ultrasound-guided thoracentesis in patients with abnormal preprocedural coagulation parameters. Chest 2013; 144 (02) 456-463
• 67 Puchalski JT, Argento AC, Murphy TE, Araujo KL, Pisani MA. The safety of thoracentesis in patients with uncorrected bleeding risk. Ann Am Thorac Soc 2013; 10 (04) 336-341
• 68 Bosch J, Abraldes JG, Berzigotti A, García-Pagan JC. The clinical use of HVPG measurements in chronic liver disease. Nat Rev Gastroenterol Hepatol 2009; 6 (10) 573-582
• 69 Casu S, Berzigotti A, Abraldes JG. , et al. A prospective observational study on tolerance and satisfaction to hepatic haemodynamic procedures. Liver Int 2015; 35 (03) 695-703
• 70 Barton RE, Rosch J, Saxon RR, Lakin PC, Petersen BD, Keller FS. TIPS: short- and long-term results: a survey of 1750 patients. Semin Intervent Radiol 1995; 12 (04) 364-367
• 71 Pillai AK, Andring B, Faulconer N. , et al. Utility of intravascular US-guided portal vein access during transjugular intrahepatic portosystemic shunt creation: retrospective comparison with conventional technique in 109 patients. J Vasc Interv Radiol 2016; 27 (08) 1154-1159
• 72 Fagiuoli S, Bruno R, Debernardi Venon W. , et al; AISF TIPS Special Conference. Consensus conference on TIPS management: techniques, indications, contraindications. Dig Liver Dis 2017; 49 (02) 121-137
• 73 Townsend JC, Heard R, Powers ER, Reuben A. Usefulness of international normalized ratio to predict bleeding complications in patients with end-stage liver disease who undergo cardiac catheterization. Am J Cardiol 2012; 110 (07) 1062-1065
• 74 Pantham G, Waghray N, Einstadter D, Finkelhor RS, Mullen KD. Bleeding risk in patients with esophageal varices undergoing transesophageal echocardiography. Echocardiography 2013; 30 (10) 1152-1155
• 75 Burger-Klepp U, Karatosic R, Thum M. , et al. Transesophageal echocardiography during orthotopic liver transplantation in patients with esophagogastric varices. Transplantation 2012; 94 (02) 192-196
• 76 Pandey CK, Saluja V, Gaurav K, Tandon M, Pandey VK, Bhadoria AS. K time & maximum amplitude of thromboelastogram predict post-central venous cannulation bleeding in patients with cirrhosis: a pilot study. Indian J Med Res 2017; 145 (01) 84-89
• 77 Müller MC, Arbous MS, Spoelstra-de Man AM. , et al. Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy before invasive procedures: a randomized clinical trial (CME). Transfusion 2015; 55 (01) 26-35 , quiz 25
• 78 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 (09) 988-993
• 79 Vanbiervliet G, Giudicelli-Bornard S, Piche T. , et al. Predictive factors of bleeding related to post-banding ulcer following endoscopic variceal ligation in cirrhotic patients: a case-control study. Aliment Pharmacol Ther 2010; 32 (02) 225-232
• 80 Bianchini M, Cavani G, Bonaccorso A. , et al. Low molecular weight heparin does not increase bleeding and mortality post-endoscopic variceal band ligation in cirrhotic patients. Liver Int 2018; . (epub ahead of print)
• 81 Adike A, Al-Qaisi M, Baffy NJ. , et al. International normalized ratio does not predict gastrointestinal bleeding after endoscopic retrograde cholangiopancreatography in patients with cirrhosis. Gastroenterol Res 2017; 10 (03) 177-181
• 82 Navaneethan U, Njei B, Zhu X, Kommaraju K, Parsi MA, Varadarajulu S. Safety of ERCP in patients with liver cirrhosis: a national database study. Endosc Int Open 2017; 5 (04) E303-E314
• 83 Huang RJ, Perumpail RB, Thosani N, Cheung R, Friedland S. Colonoscopy with polypectomy is associated with a low rate of complications in patients with cirrhosis. Endosc Int Open 2016; 4 (09) E947-E952
• 84 Koda M, Murawaki Y, Hirooka Y. , et al. Complications of radiofrequency ablation for hepatocellular carcinoma in a multicenter study: an analysis of 16 346 treated nodules in 13 283 patients. Hepatol Res 2012; 42 (11) 1058-1064
• 85 Zhou L, Zhang LZ, Wang JY. , et al. Perioperative safety analysis of transcatheter arterial chemoembolization for hepatocellular carcinoma patients with preprocedural leukopenia or thrombocytopenia. Mol Clin Oncol 2017; 7 (03) 435-442
• 86 Apfelbaum JM, Nuttal GA, Connis NT. , et al; American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management. Anesthesiology 2015; 122 (02) 241-275
• 87 Kozek-Langenecker SA, Afshari A, Albaladejo P. , et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30 (06) 270-382
• 88 Hunt BJ, Allard S, Keeling D, Norfolk D, Stanworth SJ, Pendry K. ; British Committee for Standards in Haematology. A practical guideline for the haematological management of major haemorrhage. Br J Haematol 2015; 170 (06) 788-803
• 89 Estcourt LJ, Birchall J, Allard S. , et al; British Committee for Standards in Haematology. Guidelines for the use of platelet transfusions. Br J Haematol 2017; 176 (03) 365-394
• 90 Green L, Cardigan R, Beattie C. , et al. Addendum to the British Committee for Standards in Haematology (BCSH): guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant, 2004 (Br. J Haematol 2004,126,11-28). Br J Haematol 2017; 178 (04) 646-647
• 91 Kristensen SD, Knuuti J, Saraste A. , et al; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J 2014; 35 (35) 2383-2431
• 92 Pagano D, Milojevic M, Meesters MI. , et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. Eur J Cardiothorac Surg 2018; 53 (01) 79-111
• 93 Culkin DJ, Exaire EJ, Green D. , et al. Anticoagulation and antiplatelet therapy in urological practice: ICUD/AUA review paper. J Urol 2014; 192 (04) 1026-1034
• 94 Armstrong MJ, Gronseth G, Anderson DC. , et al. Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013; 80 (22) 2065-2069
• 95 Acosta RD, Abraham NS, Chandrasekhara V. , et al; ASGE Standards of Practice Committee. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc 2016; 83 (01) 3-16
• 96 Veitch AM, Vanbiervliet G, Gershlick AH. , et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Endoscopy 2016; 48 (04) 385-402
• 97 Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. 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 (01) 310-335
• 98 Hwang JH, Shergill AK, Acosta RD. , et al; American Society for Gastrointestinal Endoscopy. The role of endoscopy in the management of variceal hemorrhage. Gastrointest Endosc 2014; 80 (02) 221-227
• 99 Tripathi D, Stanley AJ, Hayes PC. , et al; Clinical Services and Standards Committee of the British Society of Gastroenterology. U.K. guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut 2015; 64 (11) 1680-1704
• 100 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) 1253-60.e1 , 4
• 101 Cerini F, Gonzalez JM, Torres F. , et al. Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study. Hepatology 2015; 62 (02) 575-583
• 102 Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V. Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol 2015; 63 (05) 1272-1284
• 103 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365 (02) 147-156
• 104 Estcourt LJ, Desborough M, Hopewell S, Doree C, Stanworth SJ. Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia. Cochrane Database Syst Rev 2015; (12) CD011771
• 105 Finkbiner RB, Mcgovern JJ, Goldstein R, Bunker JP. Coagulation defects in liver disease and response to transfusion during surgery. Am J Med 1959; 26 (02) 199-213
• 106 Roberts HR, Cederbaum AI. The liver and blood coagulation: physiology and pathology. Gastroenterology 1972; 63 (02) 297-320
• 107 Cocchieri S, Gasbarrini G. The relevance of blood clotting tests in Chronic aggressive hepatitis. Scand J Gastroenterol 1973; 8: 97
• 108 Aledort LM. Blood clotting abnormalities in liver disease. Prog Liver Dis 1976; 5: 350-362
• 109 Mannucci PM, Mari D. Hemostasis and Liver disease. Haematologica 1981; 66 (02) 233-248
• 110 Stein SF, Harker LA. Kinetic and functional studies of platelets fibrinogen, and plasminogen in patients with hepatic cirrhosis. J Lab Clin Med 1982; Feb; 99 (02) 217-230
• 111 Friedman EW, Sussman II. Safety of invasive procedures in patients with the coagulopathy of liver disease. Clin Lab Haematol 1989; 11 (03) 199-204
• 112 Leebeek FW, Kluft C, Knot EA, de Maat MP, Wilson JH. A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis. Gastroenterology 1991; 101 (05) 1382-1390
• 113 Bell H, Odegaard OR, Andersson T, Raknerud N. Protein C in patients with alcoholic cirrhosis and other liver diseases. J Hepatol 1992; 14 (02-03): 163-167
• 114 Violi F, Ferro D, Basili S. , et al. Hyperfibrinolysis resulting from clotting activation in patients with different degrees of cirrhosis The CALC Group. Coagulation Abnormalities in Liver Cirrhosis. Hepatology 1993; 17 (01) 78-83
• 115 Arai M, Mochida S, Ohno A. , et al. Blood coagulation equilibrium in rat liver microcirculation as evaluated by endothelial cell thrombomodulin and macrophage tissue factor. Thromb Res 1995; 80 (02) 113-123
• 116 Joist JH. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state. Am J Gastroenterol 1999; 94 (10) 2801-2803
• 117 Amitrano L, Brancaccio V, Guardascione MA. , et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 2000; 31 (02) 345-348
• 118 Lisman T, Leebeek FW, Mosnier LO. , et al. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 2001; 121 (01) 131-139
• 119 Mancuso A, Fung K, Cox D, Mela M, Patch D, Burroughs AK. Assessment of blood coagulation in severe liver disease using thromboelastography: use of citrate storage versus native blood. Blood Coagul Fibrinolysis 2003; 14 (02) 211-216
• 120 Francoz C, Belghiti J, Vilgrain V. , et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54: 691-697
• 121 Tripodi A, Primignani M, Chantarangkul V. , et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006; 44 (02) 440-445
• 122 Northup PG, Sundaram V, Fallon MB. et al; Coagulation in Liver Disease Group. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost 2008; 6 (01) 2-9
• 123 Bosch J, Thabut D, Albillos A. , et al; International Study Group on rFVIIa in UGI Hemorrhage. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized controlled trial. Hepatology 2008; 47 (05) 1604-1614
• 124 Amitrano L, Guardascione MA, Menchise A. , et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol 2010; 44 (06) 448-451
• 125 Tripodi A, Primignani M, Chantarangkul V. , et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int 2013; 33 (03) 362-367
• 126 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