Download PDF
Semin Respir Crit Care Med 2018; 39(05): 598-608
DOI: 10.1055/s-0038-1673658
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Coagulation Pathways, Hemostasis, and Thrombosis in Liver Failure

Nicolas M. Intagliata
1   Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia School of Medicine, Charlottesville, Virginia
,
Jessica P.E. Davis
1   Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia School of Medicine, Charlottesville, Virginia
,
Stephen H. Caldwell
1   Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia School of Medicine, Charlottesville, Virginia
› Author Affiliations
Further Information

Publication History

Publication Date:
28 November 2018 (online)

    Permissions and Reprints

Abstract

Achieving hemostasis, preventing and treating thrombosis, and laboratory measurement of the hemostatic pathways constitute the core elements of managing the critically ill patient with liver failure. Uncontrolled bleeding in acutely decompensated cirrhosis and acute-on-chronic liver failure is probably the most familiar clinical challenge to intensivists. Bleeding in these patients can be broadly divided into pressure-driven (portal hypertension-related) bleeding with only limited dependence on hemostatic pathways and intractable mucosal/wound bleeding, which is much more directly related to a severely disturbed hemostatic system with imbalances in the coagulation cascade and the fibrinolytic system. Both types of bleeding can occur simultaneously and may even coexist with inappropriate thrombosis such as portal vein thrombosis or venous thromboembolism. Due to the fundamental role of the liver in coagulation factor synthesis and its direct and indirect regulation of nearly all aspects of the hemostatic system, laboratory measurements of coagulation pathways also constitute key aspects of all prognostic scores that guide clinical decisions and forecast optimal interventions in both acute and chronic forms of liver failure.

Keywords

coagulation - bleeding - hyperfibrinolysis - cirrhosis - anticoagulation
 

  • References

  • 1 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365 (02) 147-156
    CrossrefPubMedSearch in Google Scholar
  • 2 Lisman T, Stravitz RT. Rebalanced hemostasis in patients with acute liver failure. Semin Thromb Hemost 2015; 41 (05) 468-473
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Intagliata NM, Argo CK, Stine JG, Lisman T, Caldwell SH, Violi F. ; Faculty of the 7th International Coagulation in Liver Disease. 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 (08) 1491-1506
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Intagliata NM, Caldwell SH. Changes in hemostasis in liver disease. J Hepatol 2017; 67 (06) 1332-1333
    CrossrefPubMedSearch in Google Scholar
  • 5 Intagliata NM, Caldwell SH. The hemostatic and hematopoietic system in liver disease. In: Sanyal AJ, Boyer T, Terrault N, Lindor KD. , eds. Zakim and Boyer's Hepatology: A Textbook of Liver Disease. 7th ed. Philadelphia, PA: Elsevier; 2018: 293-300
    Search in Google Scholar
  • 6 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
    CrossrefPubMedSearch in Google Scholar
  • 7 Tripodi A, Primignani M, Lemma L, Chantarangkul V, Mannucci PM. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J Hepatol 2013; 59 (02) 265-270
    CrossrefPubMedSearch in Google Scholar
  • 8 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
    CrossrefPubMedSearch in Google Scholar
  • 9 Sinegre T, Duron C, Lecompte T. , et al. Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis. J Thromb Haemost 2018; 16 (06) 1132-1140
    CrossrefPubMedSearch in Google Scholar
  • 10 Lisman T, Bos S, Intagliata NM. Mechanisms of enhanced thrombin-generating capacity in patients with cirrhosis. J Thromb Haemost 2018; 16 (06) 1128-1131
    CrossrefPubMedSearch in Google Scholar
  • 11 Tripodi A, Primignani M, Chantarangkul V. , et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44 (02) 440-445
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 13 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
    CrossrefPubMedSearch in Google Scholar
  • 14 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
    CrossrefPubMedSearch in Google Scholar
  • 15 Lisman T, Bakhtiari K, Adelmeijer J, Meijers JC, Porte RJ, Stravitz RT. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure. J Thromb Haemost 2012; 10 (07) 1312-1319
    CrossrefPubMedSearch in Google Scholar
  • 16 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
    CrossrefPubMedSearch in Google Scholar
  • 17 Maddrey WC, Boitnott JK, Bedine MS, Weber Jr FL, Mezey E, White Jr RI. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology 1978; 75 (02) 193-199
    CrossrefPubMedSearch in Google Scholar
  • 18 Kamath PS, Wiesner RH, Malinchoc M. , et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33 (02) 464-470
    CrossrefPubMedSearch in Google Scholar
  • 19 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
    CrossrefPubMedSearch in Google Scholar
  • 20 O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97 (02) 439-445
    CrossrefPubMedSearch in Google Scholar
  • 21 Davis JPE, Northup PG, Caldwell SH, Intagliata NM. Viscoelastic testing in liver disease. Ann Hepatol 2018; 17 (02) 205-213
    CrossrefPubMedSearch in Google Scholar
  • 22 Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013; 11 (09) 1064-1074
    CrossrefPubMedSearch in Google Scholar
  • 23 Stravitz RT, Ellerbe C, Durkalski V. , et al; and the Acute Liver Failure Study Group. Bleeding complications in acute liver failure. Hepatology 2018; 67 (05) 1931-1942
    CrossrefPubMedSearch in Google Scholar
  • 24 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
    CrossrefPubMedSearch in Google Scholar
  • 25 Papatheodoridis GV, Patch D, Webster GJ, Brooker J, Barnes E, Burroughs AK. Infection and hemostasis in decompensated cirrhosis: a prospective study using thrombelastography. Hepatology 1999; 29 (04) 1085-1090
    CrossrefPubMedSearch in Google Scholar
  • 26 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; 38 (08) 1437-1441
    CrossrefPubMedSearch in Google Scholar
  • 27 De Robertis E, Kozek-Langenecker SA, Tufano R, Romano GM, Piazza O, Zito Marinosci G. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding. Minerva Anestesiol 2015; 81 (01) 65-75
    PubMedSearch in Google Scholar
  • 28 Scheiner B, Lindner G, Reiberger T. , et al. Acid-base disorders in liver disease. J Hepatol 2017; 67 (05) 1062-1073
    CrossrefPubMedSearch in Google Scholar
  • 29 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
    CrossrefPubMedSearch in Google Scholar
  • 30 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
    CrossrefPubMedSearch in Google Scholar
  • 31 Li J, Qi X, Deng H. , et al. Association of conventional haemostasis and coagulation tests with the risk of acute upper gastrointestinal bleeding in liver cirrhosis: a retrospective study. Gastroenterol Rep (Oxf) 2016; 4 (04) 315-319
    PubMedSearch in Google Scholar
  • 32 Napolitano G, Iacobellis A, Merla A. , et al. Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia. Eur J Intern Med 2017; 38: 79-82
    CrossrefPubMedSearch in Google Scholar
  • 33 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
    CrossrefPubMedSearch in Google Scholar
  • 34 Sabate A, Dalmau A. Fibrinogen: a clinical update on liver transplantation. Transplant Proc 2015; 47 (10) 2925-2928
    CrossrefPubMedSearch in Google Scholar
  • 35 Intagliata NM, Caldwell SH, Porte RJ, Lisman T. Prediction of bleeding in cirrhosis patients: is the forecast any clearer?. Hepatology 2016; 64 (03) 989-990
    CrossrefPubMedSearch in Google Scholar
  • 36 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
    CrossrefPubMedSearch in Google Scholar
  • 37 Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985; 5 (03) 419-424
    CrossrefPubMedSearch in Google Scholar
  • 38 Villanueva C, Colomo A, Bosch A. , et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368 (01) 11-21
    CrossrefPubMedSearch in Google Scholar
  • 39 Zimmon DS, Kessler RE. The portal pressure-blood volume relationship in cirrhosis. Gut 1974; 15 (02) 99-101
    CrossrefPubMedSearch in Google Scholar
  • 40 Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981; 26 (05) 388-393
    CrossrefPubMedSearch in Google Scholar
  • 41 Tripodi A, Primignani M, Mannucci PM, Caldwell SH. Changing concepts of cirrhotic coagulopathy. Am J Gastroenterol 2017; 112 (02) 274-281
    CrossrefPubMedSearch in Google Scholar
  • 42 Goodpasture EW. Fibrinolysis and chronic hepatic insufficiency. Bull Johns Hopkins Hosp 1914; 25: 330-336
    PubMedSearch in Google Scholar
  • 43 Brodsky I, Dennis LH. Evaluation of fibrinolysis in hepatic cirrhosis. Relation of serial thrombin time and euglobulin lysis time. Am J Clin Pathol 1966; 45 (01) 61-69
    CrossrefPubMedSearch in Google Scholar
  • 44 Violi F, Ferro D, Basili S. , et al. Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis. Gastroenterology 1995; 109 (02) 531-539
    CrossrefPubMedSearch in Google Scholar
  • 45 Ferro D, Celestini A, Violi F. Hyperfibrinolysis in liver disease. Clin Liver Dis 2009; 13 (01) 21-31
    CrossrefPubMedSearch in Google Scholar
  • 46 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
    CrossrefPubMedSearch in Google Scholar
  • 47 Colucci M, Binetti BM, Branca MG. , et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 2003; 38 (01) 230-237
    PubMedSearch in Google Scholar
  • 48 Joist JH. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state. Am J Gastroenterol 1999; 94 (10) 2801-2803
    PubMedSearch in Google Scholar
  • 49 Kujovich JL. Hemostatic defects in end stage liver disease. Crit Care Clin 2005; 21 (03) 563-587
    CrossrefPubMedSearch in Google Scholar
  • 50 Bezinover D, Dirkmann D, Findlay J. , et al. Perioperative coagulation management in liver transplant recipients. Transplantation 2018; 102 (04) 578-592
    CrossrefPubMedSearch in Google Scholar
  • 51 Ramsay MA, Randall HB, Burton EC. Intravascular thrombosis and thromboembolism during liver transplantation: antifibrinolytic therapy implicated?. Liver Transpl 2004; 10 (02) 310-314
    CrossrefPubMedSearch in Google Scholar
  • 52 Molenaar IQ, Warnaar N, Groen H, Tenvergert EM, Slooff MJ, Porte RJ. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2007; 7 (01) 185-194
    CrossrefPubMedSearch in Google Scholar
  • 53 Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2014; (11) CD006640
    PubMedSearch in Google Scholar
  • 54 Pabinger I, Fries D, Schöchl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr 2017; 129 (9-10): 303-316
    CrossrefPubMedSearch in Google Scholar
  • 55 De Gottardi A, Thévenot T, Spahr L. , et al. Risk of complications after abdominal paracentesis in cirrhotic patients: a prospective study. Clin Gastroenterol Hepatol 2009; 7 (08) 906-909
    CrossrefPubMedSearch in Google Scholar
  • 56 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
    CrossrefPubMedSearch in Google Scholar
  • 57 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
    CrossrefPubMedSearch in Google Scholar
  • 58 Karvellas CJ, Fix OK, Battenhouse H, Durkalski V, Sanders C, Lee WM. ; U S Acute Liver Failure Study Group. Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study. Crit Care Med 2014; 42 (05) 1157-1167
    CrossrefPubMedSearch in Google Scholar
  • 59 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
    CrossrefPubMedSearch in Google Scholar
  • 60 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
    CrossrefPubMedSearch in Google Scholar
  • 61 Vaquero J, Fontana RJ, Larson AM. , et al. Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transpl 2005; 11 (12) 1581-1589
    CrossrefPubMedSearch in Google Scholar
  • 62 Munoz SJ, Rajender Reddy K, Lee W. ; Acute Liver Failure Study Group. The coagulopathy of acute liver failure and implications for intracranial pressure monitoring. Neurocrit Care 2008; 9 (01) 103-107
    CrossrefPubMedSearch in Google Scholar
  • 63 Shami VM, Caldwell SH, Hespenheide EE, Arseneau KO, Bickston SJ, Macik BG. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl 2003; 9 (02) 138-143
    CrossrefPubMedSearch in Google Scholar
  • 64 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 (01) 129-136
    CrossrefPubMedSearch in Google Scholar
  • 65 Krisl JC, Meadows HE, Greenberg CS, Mazur JE. Clinical usefulness of recombinant activated factor VII in patients with liver failure undergoing invasive procedures. Ann Pharmacother 2011; 45 (11) 1433-1438
    CrossrefPubMedSearch in Google Scholar
  • 66 Le TV, Rumbak MJ, Liu SS, Alsina AE, van Loveren H, Agazzi S. Insertion of intracranial pressure monitors in fulminant hepatic failure patients: early experience using recombinant factor VII. Neurosurgery 2010; 66 (03) 455-458 , discussion 458
    CrossrefPubMedSearch in Google Scholar
  • 67 Thabut D, Rudler M, Rousseau G, Poynard T. Recombinant activated factor VII in chronic liver diseases: should we be afraid of thromboembolic events?. J Hepatol 2011; 55 (02) 483-485
    CrossrefPubMedSearch in Google Scholar
  • 68 Shah NL, Intagliata NM, Northup PG, Argo CK, Caldwell SH. Procoagulant therapeutics in liver disease: a critique and clinical rationale. Nat Rev Gastroenterol Hepatol 2014; 11 (11) 675-682
    PubMedSearch in Google Scholar
  • 69 Arshad F, Ickx B, van Beem RT. , et al. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial. BMC Surg 2013; 13: 22
    CrossrefPubMedSearch in Google Scholar
  • 70 Wei AC, Tung-Ping Poon R, Fan ST, Wong J. Risk factors for perioperative morbidity and mortality after extended hepatectomy for hepatocellular carcinoma. Br J Surg 2003; 90 (01) 33-41
    PubMedSearch in Google Scholar
  • 71 Massicotte L, Denault AY, Beaulieu D. , et al. Transfusion rate for 500 consecutive liver transplantations: experience of one liver transplantation center. Transplantation 2012; 93 (12) 1276-1281
    CrossrefPubMedSearch in Google Scholar
  • 72 Kahn SR, Lim W, Dunn AS. , et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis. 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e195S-226S
    CrossrefPubMedSearch in Google Scholar
  • 73 Cook D, Crowther M, Meade M. , et al. Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med 2005; 33 (07) 1565-1571
    CrossrefPubMedSearch in Google Scholar
  • 74 Lim W, Meade M, Lauzier F. , et al; PROphylaxis for ThromboEmbolism in Critical Care Trial Investigators. Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients*. Crit Care Med 2015; 43 (02) 401-410
    CrossrefPubMedSearch in Google Scholar
  • 75 Northup PG, McMahon MM, Ruhl AP. , et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol 2006; 101 (07) 1524-1528 , quiz 1680
    CrossrefPubMedSearch in Google Scholar
  • 76 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
    CrossrefPubMedSearch in Google Scholar
  • 77 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
    CrossrefPubMedSearch in Google Scholar
  • 78 Wu H, Nguyen GC. Liver cirrhosis is associated with venous thromboembolism among hospitalized patients in a nationwide US study. Clin Gastroenterol Hepatol 2010; 8 (09) 800-805
    CrossrefPubMedSearch in Google Scholar
  • 79 Ng KJ, Lee YK, Huang MY, Hsu CY, Su YC. Risks of venous thromboembolism in patients with liver cirrhosis: a nationwide cohort study in Taiwan. J Thromb Haemost 2015; 13 (02) 206-213
    CrossrefPubMedSearch in Google Scholar
  • 80 Stine JG, Niccum BA, Zimmet AN. , et al. Increased risk of venous thromboembolism in hospitalized patients with cirrhosis due to non-alcoholic steatohepatitis. Clin Transl Gastroenterol 2018; 9 (03) 140
    CrossrefPubMedSearch in Google Scholar
  • 81 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 (01) 139-148
    Thieme ConnectPubMedSearch in Google Scholar
  • 82 Søgaard KK, Horváth-Puhó E, Montomoli J, Vilstrup H, Sørensen HT. Cirrhosis is associated with an increased 30-day mortality after venous thromboembolism. Clin Transl Gastroenterol 2015; 6: e97
    CrossrefPubMedSearch in Google Scholar
  • 83 Barbar S, Noventa F, Rossetto V. , et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8 (11) 2450-2457
    CrossrefPubMedSearch in Google Scholar
  • 84 Bogari H, Patanwala AE, Cosgrove R, Katz M. Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease. Thromb Res 2014; 134 (06) 1220-1223
    CrossrefPubMedSearch in Google Scholar
  • 85 Spyropoulos AC, Anderson Jr FA, FitzGerald G. , et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011; 140 (03) 706-714
    CrossrefPubMedSearch in Google Scholar
  • 86 Decousus H, Tapson VF, Bergmann JF. , et al; IMPROVE Investigators. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011; 139 (01) 69-79
    CrossrefPubMedSearch in Google Scholar
  • 87 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
    CrossrefPubMedSearch in Google Scholar
  • 88 Shatzel J, Dulai PS, Harbin D. , et al. Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. J Thromb Haemost 2015; 13 (07) 1245-1253
    CrossrefPubMedSearch in Google Scholar
  • 89 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
    CrossrefPubMedSearch in Google Scholar
  • 90 Bechmann LP, Sichau M, Wichert M, Gerken G, Kröger K, Hilgard P. Low-molecular-weight heparin in patients with advanced cirrhosis. Liver Int 2011; 31 (01) 75-82
    CrossrefPubMedSearch in Google Scholar
  • 91 Qi X, De Stefano V, Li H, Dai J, Guo X, Fan D. Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Eur J Intern Med 2015; 26 (01) 23-29
    CrossrefPubMedSearch in Google Scholar
  • 92 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 (06) 1721-1727
    CrossrefPubMedSearch in Google Scholar
  • 93 Hum J, Shatzel JJ, Jou JH, Deloughery TG. The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis. Eur J Haematol 2017; 98 (04) 393-397
    CrossrefPubMedSearch in Google Scholar
  • 94 Intagliata NM, Maitland H, Caldwell SH. Direct oral anticoagulants in cirrhosis. Curr Treat Options Gastroenterol 2016; 14 (02) 247-256
    CrossrefPubMedSearch in Google Scholar
  • 95 Potze W, Lisman T. Issues with monitoring of unfractionated heparin in cirrhosis. Ther Drug Monit 2015; 37 (02) 279-280
    CrossrefPubMedSearch in Google Scholar
  • 96 Senzolo M, , M Sartori T Rossetto V. , et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int 2012; 32 (06) 919-927
    CrossrefPubMedSearch in Google Scholar
  • 97 Senzolo M, Rodriguez-Castro KI, Rossetto V. , et al. Increased anticoagulant response to low-molecular-weight heparin in plasma from patients with advanced cirrhosis. J Thromb Haemost 2012; 10 (09) 1823-1829
    CrossrefPubMedSearch in Google Scholar
  • 98 Potze W, Adelmeijer J, Lisman T. Decreased in vitro anticoagulant potency of Rivaroxaban and Apixaban in plasma from patients with cirrhosis. Hepatology 2015; 61 (04) 1435-1436
    CrossrefPubMedSearch in Google Scholar
  • 99 Potze W, Arshad F, Adelmeijer J. , et al. Differential in vitro inhibition of thrombin generation by anticoagulant drugs in plasma from patients with cirrhosis. PLoS One 2014; 9 (02) e88390
    CrossrefPubMedSearch in Google Scholar
  • 100 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 (05) 666-673
    CrossrefPubMedSearch in Google Scholar
  • 101 Intagliata NM, Maitland H, Pellitier S, Caldwell SH. Reversal of direct oral anticoagulants for liver transplantation in cirrhosis: a step forward. Liver Transpl 2017; 23 (03) 396-397
    CrossrefPubMedSearch in Google Scholar
  • 102 Siegal DM, Curnutte JT, Connolly SJ. , et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015; 373 (25) 2413-2424
    CrossrefPubMedSearch in Google Scholar
  • 103 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
    CrossrefPubMedSearch in Google Scholar
  • 104 Qi X, De Stefano V, Senzolo M, Xu H, Mancuso A. Splanchnic vein thrombosis: etiology, diagnosis, and treatment. Gastroenterol Res Pract 2015; 2015: 506136
    PubMedSearch in Google Scholar
  • 105 Berzigotti A, García-Criado A, Darnell A, García-Pagán JC. Imaging in clinical decision-making for portal vein thrombosis. Nat Rev Gastroenterol Hepatol 2014; 11 (05) 308-316
    CrossrefPubMedSearch in Google Scholar
  • 106 European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu EASL Clinical Practice Guidelines: vascular diseases of the liver. J Hepatol 2016; 64 (01) 179-202
    CrossrefPubMedSearch in Google Scholar
  • 107 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
    CrossrefPubMedSearch in Google Scholar
  • 108 Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol 2017; 66 (06) 1313-1326
    CrossrefPubMedSearch in Google Scholar
  • 109 Potze W, Siddiqui MS, Boyett SL. , et al. Preserved hemostatic status in patients with non-alcoholic fatty liver disease. J Hepatol 2016; 65 (05) 980-987
    CrossrefPubMedSearch in Google Scholar
  • 110 Tripodi A, Anstee QM, Sogaard KK, Primignani M, Valla DC. Hypercoagulability in cirrhosis: causes and consequences. J Thromb Haemost 2011; 9 (09) 1713-1723
    CrossrefPubMedSearch in Google Scholar
  • 111 Lin SY, Lin CL, Lin CC, Wang IK, Hsu WH, Kao CH. Risk of acute coronary syndrome and peripheral arterial disease in chronic liver disease and cirrhosis: a nationwide population-based study. Atherosclerosis 2018; 270: 154-159
    CrossrefPubMedSearch in Google Scholar
  • 112 Patel SS, Nabi E, Guzman L. , et al. Coronary artery disease in decompensated patients undergoing liver transplantation evaluation. Liver Transpl 2018; 24 (03) 333-342
    CrossrefPubMedSearch in Google Scholar
  • 113 Patel SS, Guzman L, Lin FP. , et al. Utilization of aspirin and statin in management of coronary artery disease in patients with cirrhosis undergoing liver transplant evaluation. Liver Transpl 2018; 24 (07) 872-880
    CrossrefPubMedSearch in Google Scholar
  • 114 Arshad F, Lisman T, Porte RJ. Hypercoagulability as a contributor to thrombotic complications in the liver transplant recipient. Liver Int 2013; 33 (06) 820-827
    CrossrefPubMedSearch in Google Scholar