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Semin Liver Dis 2017; 37(01): 028-032
DOI: 10.1055/s-0036-1597770
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hemostasis in Acute and Chronic Liver Disease

Armando Tripodi
1   Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano and IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
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Publication History

Publication Date:
15 February 2017 (online)

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Abstract

Acute and chronic liver diseases have long been considered prototypes of acquired hemorrhagic diseases. Over the last decade, evidence stemming from the laboratory bench and clinical practice has indicated that hemostasis abnormalities, until recently considered as the cause of bleeding in these conditions, are rebalanced to normal despite the abnormal results of the hemostasis tests such as prothrombin time and platelet counts. Consequently, the commonly used therapeutic approach—the infusion of plasma, platelets, or other prohemostatic agents—are not biologically plausible and should be reconsidered. In this article, the author reviews the evidence supporting the changing paradigm.

Keywords

hypocoagulability - hypercoagulability - thrombosis - hemorrhage
 

  • References

  • 1 Kerr R, Newsome P, Germain L , et al. Effects of acute liver injury on blood coagulation. J Thromb Haemost 2003; 1 (4) 754-759
    CrossrefPubMedGoogle Scholar
  • 2 Stravitz RT, Ellerbe C, Durkalski V, Reuben A, Lisman T, Lee WM ; Acute Liver Failure Study Group. Thrombocytopenia is associated with multi-organ system failure in patients with acute liver failure. Clin Gastroenterol Hepatol 2016; 14 (4) 613-620.e4
    CrossrefPubMedGoogle Scholar
  • 3 Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. Systematic review: acute liver failure - one disease, more than 40 definitions. Aliment Pharmacol Ther 2012; 35 (11) 1245-1256
    CrossrefPubMedGoogle Scholar
  • 4 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 (7) 1312-1319
    CrossrefPubMedGoogle Scholar
  • 5 Habib M, Roberts LN, Patel RK, Wendon J, Bernal W, Arya R. Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation. Liver Int 2014; 34 (5) 672-678
    CrossrefPubMedGoogle Scholar
  • 6 Tripodi A, Chantarangkul V, Mannucci PM. Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. Br J Haematol 2009; 147 (1) 77-82
    CrossrefPubMedGoogle Scholar
  • 7 Dahlbäck B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol 2005; 25 (7) 1311-1320
    CrossrefPubMedGoogle Scholar
  • 8 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 (2) 752-761
    CrossrefPubMedGoogle Scholar
  • 9 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 (1) 129-136
    CrossrefPubMedGoogle Scholar
  • 10 Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology 2000; 32 (4 Pt 1): 734-739
    CrossrefPubMedGoogle Scholar
  • 11 Stravitz RT, Bowling R, Bradford RL , et al. Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure. Hepatology 2013; 58 (1) 304-313
    CrossrefPubMedGoogle Scholar
  • 12 Tripodi A, Salerno F, Chantarangkul V , et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41 (3) 553-558
    CrossrefPubMedGoogle Scholar
  • 13 Bosch J, Thabut D, Bendtsen F , et al; European Study Group on rFVIIa in UGI Haemorrhage. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004; 127 (4) 1123-1130
    CrossrefPubMedGoogle Scholar
  • 14 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 (5) 1604-1614
    CrossrefPubMedGoogle Scholar
  • 15 Bendtsen F, D'Amico G, Rusch E , et al. Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-analysis of two controlled trials. J Hepatol 2014; 61 (2) 252-259
    CrossrefPubMedGoogle Scholar
  • 16 Lodge JP, Jonas S, Jones RM , et al; rFVIIa OLT Study Group. Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl 2005; 11 (8) 973-979
    CrossrefPubMedGoogle Scholar
  • 17 Planinsic RM, van der Meer J, Testa G , et al. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transpl 2005; 11 (8) 895-900
    CrossrefPubMedGoogle Scholar
  • 18 Tripodi A, Chantarangkul V, Primignani M , et al. Thrombin generation in plasma from patients with cirrhosis supplemented with normal plasma: considerations on the efficacy of treatment with fresh-frozen plasma. Intern Emerg Med 2012; 7 (2) 139-144
    PubMedGoogle Scholar
  • 19 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 (6) 2105-2111
    CrossrefPubMedGoogle Scholar
  • 20 Dargaud Y, Trzeciak MC, Bordet JC, Ninet J, Negrier C. Use of calibrated automated thrombinography +/- thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost 2006; 96 (5) 562-567
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 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 (7) 1524-1528 , quiz 1680
    CrossrefPubMedGoogle Scholar
  • 22 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 (1) 96-101
    CrossrefPubMedGoogle Scholar
  • 23 La Mura V, Tripodi A, Tosetti G , et al. Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis. Liver Int 2016; 36 (9) 1322-1330
    CrossrefPubMedGoogle Scholar
  • 24 Tripodi A, Anstee QM, Sogaard KK, Primignani M, Valla DC. Hypercoagulability in cirrhosis: causes and consequences. J Thromb Haemost 2011; 9 (9) 1713-1723
    CrossrefPubMedGoogle Scholar
  • 25 Villa E, Cammà C, Marietta M , et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143 (5) 1253-60.e1 , 4
    CrossrefPubMedGoogle Scholar
  • 26 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 (1) 53-61
    CrossrefPubMedGoogle Scholar
  • 27 Tripodi A, Primignani M, Chantarangkul V , et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44 (2) 440-445
    CrossrefPubMedGoogle Scholar
  • 28 Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD ; American Association for the Study of Liver Diseases. Liver biopsy. Hepatology 2009; 49 (3) 1017-1044
    CrossrefPubMedGoogle Scholar
  • 29 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 (3) 362-367
    CrossrefPubMedGoogle Scholar
  • 30 Gómez-Almaguer D, Herrera-Rojas MA, Jaime-Pérez JC , et al. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood 2014; 123 (25) 3906-3908
    CrossrefPubMedGoogle Scholar
  • 31 Afdhal NH, Dusheiko GM, Giannini EG , et al. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy. Gastroenterology 2014; 146 (2) 442-52.e1
    CrossrefPubMedGoogle Scholar
  • 32 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 (8) 716-724
    CrossrefPubMedGoogle Scholar
  • 33 Tripodi A, Primignani M. Nontransfusional approach to increased platelet count in patients with cirrhosis and thrombocytopenia. Hepatology 2013; 58 (3) 1177-1180
    CrossrefPubMedGoogle Scholar
  • 34 Violi F, Ferro D, Basili S , et al. Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis. Hepatology 1992; 15 (4) 672-676
    CrossrefPubMedGoogle Scholar
  • 35 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 (1) 131-139
    CrossrefPubMedGoogle Scholar
  • 36 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 (1) 230-237
    PubMedGoogle Scholar
  • 37 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
    CrossrefPubMedGoogle Scholar
  • 38 Martí-Carvajal AJ, Solà I. Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. Cochrane Database Syst Rev 2015; 6 (6) CD006007
    PubMedGoogle Scholar