Hepatology International

, Volume 12, Issue 5, pp 390–401 | Cite as

Algorithms for managing coagulation disorders in liver disease

  • R. Todd StravitzEmail author
Review Article


Patients with advanced liver disease have traditionally been considered at risk for bleeding complications. However, although bleeding in patients with cirrhosis frequently occurs due to complications of portal hypertension, research performed within the last 15 years has increasingly shown that hemostasis in patients with liver failure generally achieves a state of “rebalance”, whereby compensatory systems restore a relatively neutral or even slightly pro-thrombotic state. Much recent clinical and in vitro research has, in fact, shown over-compensation, such that patients with acute and stable chronic liver failure may have a thrombotic tendency, which may participate in the progression of liver disease and cause systemic and portal thrombosis. Investigators have started to identify differences in hemostasis in patients with unstable cirrhosis, the newly defined syndrome of acute-on-chronic liver failure (ACLF), compared to those with stable cirrhosis. The following discussion will summarize much of the background of rebalanced hemostasis in patients with cirrhosis and acute liver failure (ALF), and suggest management algorithms for coagulation abnormalities before invasive procedures, during active bleeding, and for prophylaxis and treatment of thrombotic complications.


Hemostasis Cirrhosis Acute liver failure Bleeding Thrombosis Coagulopathy 



Acute-on-chronic liver failure


A disintegrin and metalloprotease with thrombospondin type-1 motifs 13


Acute liver failure




Hepatocellular carcinoma


Intracranial pressure


International normalized ratio of the prothrombin time


Low-molecular-weight heparin


Multiorgan system failure


Portal vein thrombosis


Red blood cells


Recombinant-activated factor VII


Rotational thromboelastometry


Renal replacement therapy


Systemic inflammatory response syndrome




Tissue factor




Venous thromboembolism


VonWillebrand factor


Compliance with ethical standards

This review article does not contain any original data, only previously published studies with human and/or animal subjects, previously vetted by appropriate Institutional Review Boards.

Supplementary material

12072_2018_9886_MOESM1_ESM.pptx (40 kb)
Supplementary material 1 (PPTX 39 kb) Suppl Table 1. Hemostasis in patients with stable and unstable cirrhosis (acute decompensation and ACLF). (Adapted from Fisher, et al. J Crit Care. 2018; 43: 54) (33). Suppl Table 2. Predictors of major bleeding events in critically ill patients admitted to the ICU. 211 patients with cirrhosis, 87% of whom had ACLF, were followed prospectively for major bleeding events. Area-under-the-ROC curve analysis identified fibrinogen concentration, platelet count, and aPTT as predictors of major bleeding, but not the INR (left table). Multivariate analysis (right table) shows that a plasma fibrinogen concentration of < 60 mg/dl was most highly predictive of major bleeding. (Adapted from Drolz, et al. Hepatology. 2016; 64: 556) (35)
12072_2018_9886_MOESM2_ESM.pptx (706 kb)
Supplementary material 2 (PPTX 705 kb) Suppl Fig. 1. Thrombin generation in patients with cirrhosis and normal healthy controls. The two bars on the left depict thrombin generation in patients with cirrhosis and healthy controls, and show that cirrhotics generate less thrombin than controls due to decreased synthesis of pro-hemostatic coagulation factors (most importantly, factors V and VII) in the former. The experiments depicted in the two bars on the right include thrombomodulin (TM) in the reaction mixture, an endogenous endothelial activator of the anticoagulant, protein C. Thus, since protein C and pro-hemostatic factors are liver-derived and are proportionally decreased in patients with liver failure, thrombin generation remains “rebalanced”, as long as TM is added to the reaction mixture to activate protein C. (Adapted from Tripodi, et al. Hepatology. 2005; 41: 553) (9). Suppl Fig. 2. VonWillebrand factor levels in plasma from patients with cirrhosis and acute liver failure. In patients with cirrhosis and ALF, endothelial secretion of vonWillebrand factor (vWF) increases as a function of the severity of liver failure (left panel). In the middle and right panels, the same number of platelets is incubated in chambers with either plasma from normal healthy controls (middle panel) or plasma from patients with ALF (right panel). The increased platelet aggregation in the right compared to the middle panel demonstrates the functional significance of increased vWF in the former. (Adapted from Lisman, et al., Hepatology. 2006; 44: 53 and Hugenholtz, et al, Hepatology. 2013; 58: 752) (12, 43). Suppl Fig. 3. Risk of venous thromboembolism (VTE), deep venous thrombosis (DVT), and pulmonary embolism (PE) in patients with cirrhosis: Meta-analysis of 15 controlled studies. (Data adapted from Ambrosino, et al. Thrombosis Haemost. 2017; 117: 139) (19). Suppl Fig. 4. Patients with cirrhosis are hypercoagulable as assessed by the factor VIII/protein C ratio, in proportion to the severity of liver failure (adapted from Tripodi, et al. Gastroenterology. 2009; 137: 2105) (5). Suppl Fig. 5. Hypercoagulability in patients with cirrhosis as assessed by the FVIII/Protein C ratio predicts decompensation. The clinical course of patients with stable cirrhosis was followed over time with routine assessment for new-onset ascites and variceal bleeding. Those patients with a more hypercoagulable profile of the FVIII/Protein C ratio were more likely to decompensate than those with a lower ratio (adapted from Kalambokis, et al. J Hepatol. 2016; 65: 921) (21). Suppl Fig. 6. Anticoagulation may delay hepatic decompensation in patients with cirrhosis by slowing parenchymal extinction. The left panel describes the incidence of decompensation of stable cirrhosis in patients randomized to receive either enoxaparin or placebo, and shows a markedly delayed decompensation in the former group. A possible explanation for this observation is presented by the diagram on the right, in which the progression of parenchymal collapse of the cirrhotic liver spatially parallels thrombotic occlusion of the hepatic microvasculature within the same vascular distribution (adapted from Villa, et al. Gastroenterology. 2012; 143: 1253 (left panel) (27) and Wanless, et al. Hepatology. 1995; 21: 1238 (right panel)) (14). Suppl Fig. 7. Precipitating events and organ system failure in patients with acute-on-chronic liver failure. Based upon 303 patients with ACLF from the CLIF Consortium. (Adapted from Moreau, et al. Gastroenterology. 2013; 144: 1426) (2). Suppl Fig. 8. Blood product transfusion and bleeding complications in 1770 patients with ALF over 18 years of the ALF Study Group Registry. (Adapted from Stravitz, et al. Hepatology. 2018, in press) (37). Suppl Fig. 9. Concentration of microparticles in plasma of patients with acute liver failure. Left panel: Microparticle (MP) concentration in patients with ALI/ALF compared to normal healthy controls. Right panel: microparticle tissue factor (MPTF) activity in patients with ALI/ALF compared to normal healthy controls. MPTF activity is a measure of pro-coagulant activity, as it reflects the synergistic effect of phosphatidylserine (on the everted surface of MPs) and tissue factor on the production of factor Xa (adapted from: Stravitz, et al. Hepatology. 2013; 58: 304) (41). Suppl Fig. 10. Safety and efficacy of anticoagulation in patients with cirrhosis and portal vein thrombosis: Meta-analysis of six controlled studies (adapted from Loffredo, et al. Gastroenterology. 2017; 153: 480) (62)


  1. 1.
    Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease N Engl J Med 2011;365(2):147–156CrossRefGoogle Scholar
  2. 2.
    Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144(7):1426–1437CrossRefGoogle Scholar
  3. 3.
    Lisman T, Caldwell SH, Burroughs AK, Northup PG, Senzolo M, Stravitz RT, et al. Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol 2010;53(2):362–371CrossRefGoogle Scholar
  4. 4.
    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(9):1413–1425CrossRefGoogle Scholar
  5. 5.
    Tripodi A, Primignani M, Chantarangkul V, Dell’Era A, Clerici M, de FR, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009;137(6):2105–2111CrossRefGoogle Scholar
  6. 6.
    Lisman T, Stravitz RT. Rebalanced hemostasis in patients with acute liver failure. Semin Thromb Hemost 2015;41(5):468–473CrossRefGoogle Scholar
  7. 7.
    Bosch J, Thabut D, Bendtsen F, D’Amico G, Albillos A, Gonzalez AJ, et al. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004;127(4):1123–1130CrossRefGoogle Scholar
  8. 8.
    Bosch J, Thabut D, Albillos A, Carbonell N, Spicak J, Massard J, et al. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: a randomized, controlled trial. Hepatology 2008;47(5):1604–1614CrossRefGoogle Scholar
  9. 9.
    Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzaniga M, Primignani M, et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005;41(3):553–558CrossRefGoogle Scholar
  10. 10.
    Tripodi A, Primignani M, Chantarangkul V, Clerici M, Dell’Era A, Fabris F, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006;44(2):440–445CrossRefGoogle Scholar
  11. 11.
    Seeff LB, Everson GT, Morgan TR, Curto TM, Lee WM, Ghany MG, et al. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol 2010;8(10):877–883CrossRefGoogle Scholar
  12. 12.
    Lisman T, Bongers TN, Adelmeijer J, Janssen HL, de Maat MP, de Groot PG, et al. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 2006;44(1):53–61CrossRefGoogle Scholar
  13. 13.
    Lancellotti S, Basso M, Veca V, Sacco M, Riccardi L, Pompili M, et al. Presence of portal vein thrombosis in liver cirrhosis is strongly associated with low levels of ADAMTS-13: a pilot study. Intern Emerg Med 2016;11(7):959–967CrossRefGoogle Scholar
  14. 14.
    Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension. Hepatology 1995;21(5):1238–1247PubMedGoogle Scholar
  15. 15.
    Northup PG, McMahon MM, Ruhl AP, Altschuler SE, Volk-Bednarz A, Caldwell SH, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol 2006;101(7):1524–1528CrossRefGoogle Scholar
  16. 16.
    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):3012–3017CrossRefGoogle Scholar
  17. 17.
    Sogaard KK, Horvath-Puho E, Gronbaek H, Jepsen P, Vilstrup H, Sorensen HT. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009;104(1):96–101CrossRefGoogle Scholar
  18. 18.
    Parikh NS, Navi BB, Schneider Y, Jesudian A, Kamel H. Association between cirrhosis and stroke in a nationally representative cohort. JAMA Neurol 2017;74(8):927–932CrossRefGoogle Scholar
  19. 19.
    Ambrosino P, Tarantino L, Di MG, Paternoster M, Graziano V, Petitto M, et al. The risk of venous thromboembolism in patients with cirrhosis. A systematic review and meta-analysis. Thromb Haemost 2017;117(1):139–148CrossRefGoogle Scholar
  20. 20.
    Agarwal B, Shaw S, Shankar HM, Burroughs AK, Davenport A. Continuous renal replacement therapy (CRRT) in patients with liver disease: is circuit life different? J Hepatol 2009;51(3):504–509CrossRefGoogle Scholar
  21. 21.
    Kalambokis GN, Oikonomou A, Christou L, Kolaitis NI, Tsianos EV, Christodoulou D, et al. von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia. J Hepatol 2016;65(5):921–928CrossRefGoogle Scholar
  22. 22.
    Tsochatzis EA, Senzolo M, Germani G, Gatt A, Burroughs AK. Systematic review: portal vein thrombosis in cirrhosis. Aliment Pharmacol Ther 2010;31(3):366–374CrossRefGoogle Scholar
  23. 23.
    Ageno W, Riva N, Schulman S, Beyer-Westendorf J, Bang SM, Senzolo M, et al. Long-term clinical outcomes of splanchnic vein thrombosis: results of an international registry. JAMA Intern Med 2015;175(9):1474–1480CrossRefGoogle Scholar
  24. 24.
    Nery F, Chevret S, Condat B, de RE, Boudaoud L, Rautou PE, et al. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 2015;61(2):660–667CrossRefGoogle Scholar
  25. 25.
    Garcia-Pagan JC, Valla DC. Portal vein thrombosis: a predictable milestone in cirrhosis? J Hepatol 2009;51(4):632–634CrossRefGoogle Scholar
  26. 26.
    Carnevale R, Raparelli V, Nocella C, Bartimoccia S, Novo M, Severino A, et al. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis. J Hepatol 2017;67(5):950–956CrossRefGoogle Scholar
  27. 27.
    Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012;143(5):1253–1260CrossRefGoogle Scholar
  28. 28.
    Chau TN, Chan YW, Patch D, Tokunaga S, Greenslade L, Burroughs AK. Thrombelastographic changes and early rebleeding in cirrhotic patients with variceal bleeding. Gut 1998;43(2):267–271CrossRefGoogle Scholar
  29. 29.
    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(4):463–470CrossRefGoogle Scholar
  30. 30.
    Tapper EB, Robson SC, Malik R. Coagulopathy in cirrhosis—the role of the platelet in hemostasis. J Hepatol 2013;59(4):889–890CrossRefGoogle Scholar
  31. 31.
    Rautou PE, Vion AC, Luyendyk JP, Mackman N. Circulating microparticle tissue factor activity is increased in patients with cirrhosis. Hepatology 2014;60(5):1793–1795CrossRefGoogle Scholar
  32. 32.
    Rautou PE, Bresson J, Sainte-Marie Y, Vion AC, Paradis V, Renard JM, et al. Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis. Gastroenterology 2012;143(1):166–176CrossRefGoogle Scholar
  33. 33.
    Fisher C, Patel VC, Stoy SH, Singanayagam A, Adelmeijer J, Wendon J, 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;43:54–60CrossRefGoogle Scholar
  34. 34.
    Blasi A, Calvo A, Hernandez M, Reverter JC, Fernandez J, Cardenas A. Prosepective evaluation of the thromboelastography (ROTEM®) profile in patients with acute-on-chronic liver failure and decompensated cirrhosis. Hepatology 2018;66:300AGoogle Scholar
  35. 35.
    Drolz A, Horvatits T, Roedl K, Rutter K, Staufer K, Kneidinger N, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology 2016;64(2):556–568CrossRefGoogle Scholar
  36. 36.
    Harrison PM, O’Grady JG, Keays RT, Alexander GJ, Williams R. Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure. BMJ 1990;301(6758):964–966CrossRefGoogle Scholar
  37. 37.
    Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, et al. Bleeding complications in acute liver failure. Hepatology 2018;67(5):1931–1942CrossRefGoogle Scholar
  38. 38.
    Stravitz RT, Ellerbe C, Durkalski V, Reuben A, Lisman T, Lee WM. Thrombocytopenia is associated with multi-organ system failure in patients with acute liver failure. Clin Gastroenterol Hepatol 2016;14(4):613–620CrossRefGoogle Scholar
  39. 39.
    Valla D, Flejou JF, Lebrec D, Bernuau J, Rueff B, Salzmann JL, et al. Portal hypertension and ascites in acute hepatitis: clinical, hemodynamic and histological correlations. Hepatology 1989;10(4):482–487CrossRefGoogle Scholar
  40. 40.
    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):734–739CrossRefGoogle Scholar
  41. 41.
    Stravitz RT, Bowling R, Bradford RL, Key NS, Glover S, Thacker LR, et al. Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure. Hepatology 2013;58(1):304–313CrossRefGoogle Scholar
  42. 42.
    Stravitz RT, Lisman T, Luketic VA, Sterling RK, Puri P, Fuchs M, et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012;56(1):129–136CrossRefGoogle Scholar
  43. 43.
    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):752–761CrossRefGoogle Scholar
  44. 44.
    Williams AM, Langley PG, Osei-Hwediah J, Wendon JA, Hughes RD. Hyaluronic acid and endothelial damage due to paracetamol-induced hepatotoxicity. Liver Int 2003;23(2):110–115CrossRefGoogle Scholar
  45. 45.
    Agarwal B, Wright G, Gatt A, Riddell A, Vemala V, Mallett S, et al. Evaluation of coagulation abnormalities in acute liver failure. J Hepatol 2012;57(4):780–786CrossRefGoogle Scholar
  46. 46.
    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):1312–1319CrossRefGoogle Scholar
  47. 47.
    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):672–678CrossRefGoogle Scholar
  48. 48.
    Owens AP III, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011;108(10):1284–1297CrossRefGoogle Scholar
  49. 49.
    Key NS. Analysis of tissue factor positive microparticles. Thromb Res 2010;125(Suppl 1):S42–S45CrossRefGoogle Scholar
  50. 50.
    Hillenbrand P, Parbhoo SP, Jedrychowski A, Sherlock S. Significance of intravascular coagulation and fibrinolysis in acute hepatic failure. Gut 1974;15(2):83–88CrossRefGoogle Scholar
  51. 51.
    Ganey PE, Luyendyk JP, Newport SW, Eagle TM, Maddox JF, Mackman N, Roth RA. Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice. Hepatology 2007;46(4):1177–1186CrossRefGoogle Scholar
  52. 52.
    Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991;324(26):1852–1857CrossRefGoogle Scholar
  53. 53.
    De PL, Bianchini M, Montalti R, De MN, Di MT, Begliomini B, et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial. Hepatology 2016;63(2):566–573CrossRefGoogle Scholar
  54. 54.
    Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46(3):922–938CrossRefGoogle Scholar
  55. 55.
    Castaneda B, Morales J, Lionetti R, Moitinho E, Andreu V, Perez-Del-Pulgar S, et al. Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats. Hepatology 2001;33(4):821–825CrossRefGoogle Scholar
  56. 56.
    Giannini EG, Stravitz RT, Caldwell SH. Correction of hemostatic abnormalities and portal pressure variations in patients with cirrhosis. Hepatology 2014;60(4):1442CrossRefGoogle Scholar
  57. 57.
    Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368(1):11–21CrossRefGoogle Scholar
  58. 58.
    Nadim MK, Durand F, Kellum JA, Levitsky J, O’Leary JG, Karvellas CJ, et al. Management of the critically ill patient with cirrhosis: a multidisciplinary perspective. J Hepatol 2016;64(3):717–735CrossRefGoogle Scholar
  59. 59.
    Lisman T, Kleiss S, Patel VC, Fisher C, Adelmeijer J, Bos S, Singanayagam A, Stoy SH, Shawcross DL, Bernal W. In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis. Liver Int 2018. (epub ahead of print) CrossRefPubMedGoogle Scholar
  60. 60.
    Valla DC, Rautou PE. The coagulation system in patients with end-stage liver disease. Liver Int 2015;35(Suppl 1):139–144CrossRefGoogle Scholar
  61. 61.
    Senzolo M, Sartori M, Rossetto V, Burra P, Cillo U, Boccagni P, et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int 2012;32(6):919–927CrossRefGoogle Scholar
  62. 62.
    Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology 2017;153(2):480–487CrossRefGoogle Scholar
  63. 63.
    Luca A, Miraglia R, Caruso S, Milazzo M, Sapere C, Maruzzelli L, et al. Short- and long-term effects of the transjugular intrahepatic portosystemic shunt on portal vein thrombosis in patients with cirrhosis. Gut 2011;60(6):846–852CrossRefGoogle Scholar
  64. 64.
    Qi X, Han G, Fan D. Management of portal vein thrombosis in liver cirrhosis. Nat Rev Gastroenterol Hepatol 2014;11(7):435–446CrossRefGoogle Scholar
  65. 65.
    Cerini F, Gonzalez JM, Torres F, Puente A, Casas M, Vinaixa C, et al. Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study. Hepatology 2015;62(2):575–83CrossRefGoogle Scholar
  66. 66.
    Senzolo M, Rodriguez-Castro KI, Rossetto V, Radu C, Gavasso S, Carraro P, et al. Increased anticoagulant response to low-molecular-weight heparin in plasma from patients with advanced cirrhosis. J Thromb Haemost 2012;10(9):1823–1829CrossRefGoogle Scholar
  67. 67.
    Bechmann LP, Sichau M, Wichert M, Gerken G, Kroger K, Hilgard P. Low-molecular-weight heparin in patients with advanced cirrhosis. Liver Int 2011;31(1):75–82CrossRefGoogle Scholar
  68. 68.
    Intagliata NM, Henry ZH, Maitland H, Shah NL, Argo CK, Northup PG, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci 2016;61(6):1721–1727CrossRefGoogle Scholar
  69. 69.
    Potze W, Adelmeijer J, Lisman T. Decreased in vitro anticoagulant potency of rivaroxaban and apixaban in plasma from patients with cirrhosis. Hepatology 2015;61(4):1435–1436CrossRefGoogle Scholar
  70. 70.
    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(2):138–143CrossRefGoogle Scholar
  71. 71.
    Pavese P, Bonadona A, Beaubien J, Labrecque P, Pernod G, Letoublon C, et al. FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis: a report of four cases. Can J Anaesth 2005;52(1):26–29CrossRefGoogle Scholar
  72. 72.
    Patel S, Wendon J. Regional citrate anticoagulation in patients with liver failure–time for a rethink? Crit Care 2012;16(5):153CrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2018

Authors and Affiliations

  1. 1.Section of Hepatology, Hume-Lee Transplant CenterVirginia Commonwealth UniversityRichmondUSA

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