The Hemostatic System in Patients with Cirrhosis, Monitoring of Coagulation and Management of Bleeding

  • Daniel DirkmannEmail author


Acute on chronic liver failure (ACLF) has both a direct and an indirect impact on the entire hemostatic system. According to current understanding, cirrhosis and liver failure both evoke several changes in pro- and anti-coagulant as well as pro- and anti-fibrinolytic mechanisms, resulting in a fragile rebalanced state of hemostasis. However, standard laboratory coagulation assays frequently suggest hypocoagulability and are commonly understood as indicating a state of auto-anticoagulation and a risk of spontaneous bleeding. Nevertheless, patients suffering from ACLF are more frequently subject to thromboembolic events than to spontaneous coagulopathic bleeding episodes, suggesting implications for thromboprophylaxis. Comprehensive coagulation testing is required to characterize the changes counterbalancing deficiencies in certain coagulation factors, hypofibrinogenemia, and thrombocytopenia. A clear understanding of these rebalanced, highly specific alterations is essential to providing adequate perioperative care for the patients thus affected. In the perioperative setting, viscoelastic testing is increasingly being used to guide hemostatic interventions in order to provide individualized therapy. Furthermore, highly purified coagulation factor concentrates are increasingly being used in rendering such therapy and with the aim of reducing allogeneic blood transfusions, which have been found to be associated with adverse outcomes in patients undergoing liver transplantation.


Coagulation Hemostasis Coagulopathy Thrombocytopenia Standard laboratory coagulation analyses Viscoelastic coagulation assays Hyperfibrinolysis 


  1. 1.
    Stassen JM, Arnout J, Deckmyn H. The hemostatic system. Curr Med Chem. 2004;11(17):2245–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Pereira SP, Langley PG, Williams R. The management of abnormalities of hemostasis in acute liver failure. Semin Liver Dis. © 1996 by Thieme Medical Publishers, Inc; 1996;16(4):403–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Amitrano L, Guardascione MA, Brancaccio V, Balzano A. Coagulation disorders in liver disease. Semin Liver Dis. 2002;22(1):83–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Ishitani M, Angle J, Bickston S, Caldwell S, Isaacs R, Pruett T. Liver transplantation: incidence and management of deep venous thrombosis and pulmonary emboli. Transplant Proc. 1997;29(7):2861–3.PubMedCrossRefGoogle Scholar
  5. 5.
    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):1524–8; quiz 1680.PubMedCrossRefGoogle Scholar
  6. 6.
    Valla DC. Thrombosis and anticoagulation in liver disease. Hepatology. 2008;47(4):1384–93. Wiley Subscription Services, Inc., A Wiley Company.PubMedCrossRefGoogle Scholar
  7. 7.
    Warnaar N, Molenaar IQ, Colquhoun SD, Slooff MJH, Sherwani S, de Wolf AM, et al. Intraoperative pulmonary embolism and intracardiac thrombosis complicating liver transplantation: a systematic review. J Thromb Haemost. 2008;6(2):297–302. Blackwell Publishing Ltd.PubMedCrossRefGoogle Scholar
  8. 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(1):96–101.PubMedCrossRefGoogle Scholar
  9. 9.
    Caldwell SH, Hoffman M, Lisman T, Macik BG, Northup PG, Reddy KR, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 2006;44(4):1039–46. Wiley Subscription Services, Inc., A Wiley Company.PubMedCrossRefGoogle Scholar
  10. 10.
    Lisman T, Leebeek FWG. Hemostatic alterations in liver disease: a review on pathophysiology, clinical consequences, and treatment. Dig Surg. 2007;24(4):250–8. Karger Publishers.PubMedCrossRefGoogle Scholar
  11. 11.
    Mannucci PM. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No. J Thromb Haemost. 2006;4(4):721–3. Blackwell Science Inc.PubMedCrossRefGoogle Scholar
  12. 12.
    Tripodi A, Mannucci PM. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J Hepatol. 2007;46(4):727–33.PubMedCrossRefGoogle Scholar
  13. 13.
    Pereira SP, Rowbotham D, Fitt S, Shearer MJ, Wendon J, Williams R. Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease. J Hepatol. 2005;42(3):365–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Langley PG, Williams R. Physiological inhibitors of coagulation in fulminant hepatic failure. Blood Coagul Fibrinolysis. 1992;3(3):243–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Hollestelle MJ, Loots CM, Squizzato A, Renné T, Bouma BJ, De Groot PG, et al. Decreased active von Willebrand factor level owing to shear stress in aortic stenosis patients. J Thromb Haemost. 2011;9(5):953–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Turner N, Nolasco L, Tao Z, Dong J-F, Moake J. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost. 2006;4(6):1396–404.PubMedCrossRefGoogle Scholar
  17. 17.
    Uemura M, Fujimura Y, Matsumoto M, Ishizashi H, Kato S, Matsuyama T, et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost. 2008;99(6):1019–29.PubMedCrossRefGoogle Scholar
  18. 18.
    Kerr R, Newsome P, Germain L, Thomson E, Dawson P, Stirling D, et al. Effects of acute liver injury on blood coagulation. J Thromb Haemost. 2003;1(4):754–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Peck-Radosavljevic M, Wichlas M, Zacherl J, Stiegler G, Stohlawetz P, Fuchsjäger M, et al. Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production. Blood. 2000;95(3):795–801.PubMedGoogle Scholar
  20. 20.
    García-Suárez J, Burgaleta C, Hernanz N, Albarran F, Tobaruela P, Alvarez-Mon M. HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy. Br J Haematol. 2000;110(1):98–103.PubMedCrossRefGoogle Scholar
  21. 21.
    Ballard HS. Hematological complications of alcoholism. Alcohol Clin Exp Res. 1989;13(5):706–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Nagamine T, Ohtuka T, Takehara K, Arai T, Takagi H, Mori M. Thrombocytopenia associated with hepatitis C viral infection. J Hepatol. 1996;24(2):135–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Feistauer SM, Penner E, Mayr WR, Panzer S. Target platelet antigens of autoantibodies in patients with primary biliary cirrhosis. Hepatology. 1997;25(6):1343–5. Wiley Subscription Services, Inc. A Wiley Company.PubMedCrossRefGoogle Scholar
  24. 24.
    Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008;48(6):1000–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Lisman T, Bongers TN, Janssen HLA, de Maat MPM, de Groot PG, Leebeek FWG. Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology. 2006;44(1):53–61.PubMedCrossRefGoogle Scholar
  26. 26.
    Hugenholtz GCG, Adelmeijer J, Meijers JCM, 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):752–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Reuken PA, Kussmann A, Kiehntopf M, Budde U, Stallmach A, Claus RA, et al. Imbalance of von Willebrand factor and its cleaving protease ADAMTS13 during systemic inflammation superimposed on advanced cirrhosis. Liver Int. 2015;35(1):37–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Robson SC, Kahn D, Kruskal J, Bird AR, Kirsch RE. Disordered hemostasis in extrahepatic portal hypertension. Hepatology. 1993;18(4):853–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Rubin MH, Weston MJ, Bullock G, Roberts J, Langley PG, White YS, et al. Abnormal platelet function and ultrastructure in fulminant hepatic failure. Q J Med. 1977;46(183):339–52.PubMedGoogle Scholar
  30. 30.
    Escolar G, Cases A, Viñas M, Pino M, Calls J, Cirera I, et al. Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100 ): influence of hematocrit elevation. Haematologica. 1999;84(7):614–9.PubMedGoogle Scholar
  31. 31.
    Lisman T, Adelmeijer J, De Groot PG, HLA J, FWG L. No evidence for an intrinsic platelet defect in patients with liver cirrhosis – studies under flow conditions. J Thromb Haemost. 2006;4(9):2070–2. Blackwell Publishing Ltd.PubMedCrossRefGoogle Scholar
  32. 32.
    Pihusch R, Rank A, Göhring P, Pihusch M, Hiller E, Beuers U. Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease. J Hepatol. 2002;37(5):548–55.PubMedCrossRefGoogle Scholar
  33. 33.
    Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev. 2007;21(3):131–42.PubMedCrossRefGoogle Scholar
  34. 34.
    Wolberg AS. Plasma and cellular contributions to fibrin network formation, structure and stability. Blood. 2010;16 Suppl 3(Suppl. 1):7–12. Blackwell Publishing Ltd.Google Scholar
  35. 35.
    Segal H, Cottam S, Potter D, Hunt BJ. Coagulation and fibrinolysis in primary biliary cirrhosis compared with other liver disease and during orthotopic liver transplantation. Hepatology. 1997;25(3):683–8. Wiley Subscription Services, Inc. A Wiley Company.PubMedCrossRefGoogle Scholar
  36. 36.
    Senzolo M, Burra P, Cholongitas E, Burroughs AK. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol. 2006;12(48):7725–36. Baishideng Publishing Group Inc.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Martinez J, MacDonald KA, Palascak JE. The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains. Blood. 1983;61(6):1196–202.PubMedGoogle Scholar
  38. 38.
    Huber K, Kirchheimer JC, Korninger C, Binder BR. Hepatic synthesis and clearance of components of the fibrinolytic system in healthy volunteers and in patients with different stages of liver cirrhosis. Thromb Res. 1991;62(5):491–500.PubMedCrossRefGoogle Scholar
  39. 39.
    Agarwal S, Joyner KA, Swaim MW. Ascites fluid as a possible origin for hyperfibrinolysis in advanced liver disease. Am J Gastroenterol. 2000;95(11):3218–24.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Pernambuco JR, Langley PG, Hughes RD, Izumi S, Williams R. Activation of the fibrinolytic system in patients with fulminant liver failure. Hepatology. 1993;18(6):1350–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Lisman T, Bakhtiari K, Adelmeijer J, Meijers JCM, 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):1312–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Lisman T, Leebeek FW, Mosnier LO, Bouma BN, Meijers JC, Janssen HL, et al. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology. 2001;121(1):131–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Haas T, Spielmann N, Mauch J, Madjdpour C, Speer O, Schmugge M, et al. Comparison of thromboelastometry (ROTEM(R)) with standard plasmatic coagulation testing in paediatric surgery. Br J Anaesth. 2011;108(1):36–41.PubMedCrossRefGoogle Scholar
  44. 44.
    Davenport R, Manson J, De'Ath H, Platton S, Coates A, Allard S, et al. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med. 2011;39(12):2652–8.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Toulon P, Ozier Y, Ankri A, Fléron M-H, Leroux G, Samama C-M. Point-of-care versus central laboratory coagulation testing during haemorrhagic surgery. A Multicenter Study. Thromb Haemost. 2009;101(2):394–401.PubMedCrossRefGoogle Scholar
  46. 46.
    Haas T, Fries D, Tanaka KA, Asmis L, Curry NS, Schöchl H. Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence? Br J Anaesth. 2015;114(2):217–24. Oxford University PressPubMedCrossRefGoogle Scholar
  47. 47.
    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;122:241–75.Google Scholar
  48. 48.
    Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20(1):1–55.CrossRefGoogle Scholar
  49. 49.
    PA O, Aas K. The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin. Scand J Clin Lab Invest. 1951;3(3):201–8.CrossRefGoogle Scholar
  50. 50.
    Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci. 1981;26(5):388–93.PubMedCrossRefGoogle Scholar
  51. 51.
    Massicotte L, Thibeault L, Roy A. Classical notions of coagulation revisited in relation with blood losses, transfusion rate for 700 consecutive liver transplantations. Semin Thromb Hemost. 2015;41(5):538–46. Thieme Medical Publishers.PubMedCrossRefGoogle Scholar
  52. 52.
    Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464–70. WB Saunders.PubMedCrossRefGoogle Scholar
  53. 53.
    Kitchens CS. To bleed or not to bleed? Is that the question for the PTT? J Thromb Haemost. 2005;3(12):2607–11. Blackwell Science Inc.PubMedCrossRefGoogle Scholar
  54. 54.
    BOWYER A, KITCHEN S, Makris M. The responsiveness of different APTT reagents to mild factor VIII, IX and XI deficiencies. Int Jnl Lab Hem. 2010;33(2):154–8.CrossRefGoogle Scholar
  55. 55.
    Mitsuguro M, Okamoto A, Shironouchi Y, Sano M, Miyata S, Neki R, et al. Effects of factor VIII levels on the APTT and anti-Xa activity under a therapeutic dose of heparin. Int J Hematol. 2014;101(2):119–25.PubMedCrossRefGoogle Scholar
  56. 56.
    Ng VL. Prothrombin time and partial thromboplastin time assay considerations. Clin Lab Med. 2009;29(2):253–63.PubMedCrossRefGoogle Scholar
  57. 57.
    Palascak JE, Martinez J. Dysfibrinogenemia associated with liver disease. J Clin Invest. 1977;60(1):89–95. American Society for Clinical Investigation.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    de Maat MPM, Nieuwenhuizen W, Knot EAR, 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(4):353–62.PubMedCrossRefGoogle Scholar
  59. 59.
    Thakrar SV, Mallett SV. Thrombocytopenia in cirrhosis: impact of fibrinogen on bleeding risk. World J Hepatol. 2017;9(6):318–9.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Dötsch TM, Dirkmann D, Bezinover D, Hartmann M, Treckmann JW, Paul A, et al. Assessment of standard laboratory tests and rotational thromboelastometry for the prediction of postoperative bleeding in liver transplantation. Br J Anaesth. 2017;119(3):402–10.PubMedCrossRefGoogle Scholar
  61. 61.
    Blasi A, Beltran J, Pereira A, Martinez-Palli G, Torrents A, Balust J, et al. An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation. Transfusion. 2012;52(9):1989–98. Blackwell Publishing Inc.PubMedCrossRefGoogle Scholar
  62. 62.
    Lancé MD. A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis. Thromb J. 2015;13(1):2607–6.CrossRefGoogle Scholar
  63. 63.
    Hemker HC, Dieri Al R, Béguin S. Thrombin generation assays: accruing clinical relevance. Curr Opin Hematol. 2004;11(3):170–5.PubMedCrossRefGoogle Scholar
  64. 64.
    Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011;365(2):147–56.PubMedCrossRefGoogle Scholar
  65. 65.
    Gatt A, Riddell A, Calvaruso V, Tuddenham EG, Makris M, Burroughs AK. Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy. J Thromb Haemost. 2010;8(9):1994–2000. Blackwell Publishing Ltd.PubMedCrossRefGoogle Scholar
  66. 66.
    Tripodi A, Legnani C, Lemma L, Cosmi B, Palareti G, Chantarangkul V, et al. Abnormal Protac-induced coagulation inhibition chromogenic assay results are associated with an increased risk of recurrent venous thromboembolism. J Thromb Thrombolysis. 2010;30(2):215–9. Springer US.PubMedCrossRefGoogle Scholar
  67. 67.
    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;59:265.PubMedCrossRefGoogle Scholar
  68. 68.
    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):440–5. Wiley Subscription Services, Inc., A Wiley Company.PubMedCrossRefGoogle Scholar
  69. 69.
    Tripodi A, Cappellini MD, Chantarangkul V, Padovan L, Fasulo MR, Marcon A, et al. Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma. Haematologica. 2009;94(11):1520–7.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Tripodi A, Primignani M, Chantarangkul V, Lemma L, Jovani M, Rebulla P, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int. 2012;33(3):362–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Mosnier LO. Platelet factor 4 inhibits Thrombomodulin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) by thrombin. J Biol Chem. 2010;286(1):502–10.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Hartert H. Blutgerunngunsstudien mit dem Thrombelastographen, einem neuen Untersuchungsverfahren. Klin Wochenschr. 1948;26(37/38):577–83.PubMedCrossRefGoogle Scholar
  73. 73.
    Herbstreit F, Winter EM, Peters J, Hartmann M. Monitoring of haemostasis in liver transplantation: comparison of laboratory based and point of care tests. Anaesthesia. 2010;65(1):44–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Blasi A, Muñoz G, de Soto I, Mellado R, Taura P, Rios J, et al. Reliability of thromboelastometry for detecting the safe coagulation threshold in patients taking acenocoumarol after elective heart valve replacement. Thromb Res. 2015;136(3):669–72.PubMedCrossRefGoogle Scholar
  75. 75.
    Larsen OH, Fenger-Eriksen C, Christiansen K, Ingerslev J, Sørensen B. Diagnostic performance and therapeutic consequence of thromboelastometry activated by kaolin versus a panel of specific reagents. Anesthesiology. 2011;115(2):294–302.PubMedCrossRefGoogle Scholar
  76. 76.
    Sakai T, Matsusaki T, Dai F, Tanaka KA, Donaldson JB, Hilmi IA, et al. Pulmonary thromboembolism during adult liver transplantation: incidence, clinical presentation, outcome, risk factors, and diagnostic predictors. Br J Anaesth. 2012;108(3):469–77.PubMedCrossRefGoogle Scholar
  77. 77.
    Song J-G, Jeong S-M, Jun I-G, Lee H-M, Hwang G-S. Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation. Br J Anaesth. 2014;112(2):290–7. Oxford University Press.PubMedCrossRefGoogle Scholar
  78. 78.
    Coakley M, Reddy K, Mackie I, Mallett S. Transfusion triggers in Orthotopic liver transplantation: a comparison of the Thromboelastometry analyzer, the Thromboelastogram, and conventional coagulation tests. J Cardiothorac Vasc Anesth. 2006;20(4):548–53.PubMedCrossRefGoogle Scholar
  79. 79.
    Kirchner C, Dirkmann D, Treckmann JW, Paul A, Hartmann M, Saner FH, et al. Coagulation management with factor concentrates in liver transplantation: a single-center experience. Transfusion. 2014;54(10 Pt 2):2760–8.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Görlinger K. Coagulation management during liver transplantation. Hamostaseologie. 2006;26(3 Suppl 1):64–76.Google Scholar
  81. 81.
    Roullet S, Pillot J, Freyburger G, Biais M, Quinart A, Rault A, et al. Rotation thromboelastometry detects thrombocytopenia and hypofibrinogenaemia during orthotopic liver transplantation. Br J Anaesth. 2010;104(4):422–8. Oxford University Press.PubMedCrossRefGoogle Scholar
  82. 82.
    Jeong S-M, Song J-G, Seo H, Choi J-H, Jang D-M, Hwang G-S. Quantification of both platelet count and fibrinogen concentration using maximal clot firmness of Thromboelastometry during liver transplantation. Transplant Proc. 2015;47(6):1890–5.PubMedCrossRefGoogle Scholar
  83. 83.
    Pereboom ITA, de Boer MT, Haagsma EB, Hendriks HGD, Lisman T, Porte RJ. Platelet transfusion during liver transplantation is associated with increased postoperative mortality due to acute lung injury. Anesth Analg. 2009;108(4):1083–91.PubMedCrossRefGoogle Scholar
  84. 84.
    Görlinger K, Dirkmann D, Solomon C, Hanke AA. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability. Br J Anaesth. 2013;110(2):222–30.PubMedCrossRefGoogle Scholar
  85. 85.
    Dirkmann D, Görlinger K, Peters J. Assessment of early thromboelastometric variables from extrinsically activated assays with and without aprotinin for rapid detection of fibrinolysis. Anesth Analg. 2014;119(3):533–42.PubMedCrossRefGoogle Scholar
  86. 86.
    Mallett SV, Armstrong M. Point-of-care monitoring of haemostasis. Anaesthesia. 2015;70 Suppl 1(Suppl 4):73–7, e25–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Wang S-C, Shieh J-F, Chang K-Y, Chu Y-C, Liu C-S, Loong C-C, et al. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc. 2010;42(7):2590–3.PubMedCrossRefGoogle Scholar
  88. 88.
    Kozek-Langenecker SA, Ahmed AB, Afshari A, Albaladejo P, Aldecoa C, Barauskas G, et al. Management of severe perioperative bleeding. Eur J Anaesthesiol. 2017;34(6):332–95.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Mallett SV, Chowdary P, Burroughs AK. Clinical utility of viscoelastic tests of coagulation in patients with liver disease. Liver Int. 2013;33(7):961–74.PubMedCrossRefGoogle Scholar
  90. 90.
    Corredor C, Wasowicz M, Karkouti K, Sharma V. The role of point-of-care platelet function testing in predicting postoperative bleeding following cardiac surgery: a systematic review and meta-analysis. Anaesthesia. 2015;70(6):715–31.PubMedCrossRefGoogle Scholar
  91. 91.
    Schulte am Esch J, Akyildiz A, Tustas RY, Ganschow R, Schmelzle M, Krieg A, et al. ADP-dependent platelet function prior to and in the early course of pediatric liver transplantation and persisting thrombocytopenia are positively correlated with ischemia/reperfusion injury. Transpl Int. 2010;23(7):745–52.PubMedCrossRefGoogle Scholar
  92. 92.
    Esch JSA, Jurk K, Knoefel WT, Roeder G, Voss H, Tustas RY, et al. Platelet activation and increased tissue factor expression on monocytes in reperfusion injury following orthotopic liver transplantation. Platelets. 2010;21(5):348–59.PubMedCrossRefGoogle Scholar
  93. 93.
    Femia EA, Scavone M, Lecchi A, Cattaneo M. Effect of platelet count on platelet aggregation measured with impedance aggregometry (multiplate™ analyzer) and with light transmission aggregometry. J Thromb Haemost. 2013;11(12):2193–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Kakouros N, Kickler TS, Laws KM, Rade JJ. Hematocrit alters VerifyNow P2Y12 assay results independently of intrinsic platelet reactivity and clopidogrel responsiveness. J Thromb Haemost. 2013;11(10):1814–22.PubMedCrossRefGoogle Scholar
  95. 95.
    Janssen PWA, Bergmeijer TO, Godschalk TC, Le TTD, Breet NJ, Kelder JC, et al. The effect of correcting VerifyNow P2Y12 assay results for hematocrit in patients undergoing percutaneous coronary interventions. J Thromb Haemost. 2017;15(4):618–23.PubMedCrossRefGoogle Scholar
  96. 96.
    Le Quellec S, Bordet JC, Negrier C, Dargaud Y. Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response. Thromb Haemost. 2016;116(4):638–50. Schattauer Publishers.PubMedGoogle Scholar
  97. 97.
    Karon BS, Tolan NV, Koch CD, Wockenfus AM, Miller RS, Lingineni RK, et al. Precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet agent therapy. Clin Chem. 2014;60(12):1524–31.PubMedCrossRefGoogle Scholar
  98. 98.
    Saner FH, Abeysundara L, Hartmann M, Mallett SV. Rational approach to transfusion in liver transplantation. Minerva Anestesiol. 2018;84(3):378–88.Google Scholar
  99. 99.
    Giannini EG, Stravitz RT, Caldwell SH. Correction of hemostatic abnormalities and portal pressure variations in patients with cirrhosis. Hepatology. 2014;60:1442.PubMedCrossRefGoogle Scholar
  100. 100.
    Sarani B, Dunkman WJ, Dean L, Sonnad S, Rohrbach JI, Gracias VH. Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Crit Care Med. 2008;36:1114–8.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion. 2006;46:1279–85.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Abuelkasem E, Hasan S, Mazzeffi MA, Planinsic RM, Sakai T, Tanaka KA. Reduced requirement for prothrombin complex concentrate for the restoration of thrombin generation in plasma from liver transplant recipients. Anesth Analg. 2017;125:609–15.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    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;63:566–73.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Leon-Justel A, Noval-Padillo JA, Alvarez-Rios AI, et al. Point-of-care haemostasis monitoring during liver transplantation reduces transfusion requirements and improves patient outcome. Clin Chim Acta. 2015;446:277–83.PubMedCrossRefGoogle Scholar
  105. 105.
    Hofmann M, Schumann C, Zimmer G, Henzel K, Locher U, Leuschner U. LUV's lipid composition modulates diffusion of bile acids. Chem Phys Lipids. 2001;110:165–71.PubMedCrossRefGoogle Scholar
  106. 106.
    Scherer R, Gille A, Erhard J, Paar D, Kox WJ. The effect of substitution with AT III- and PPSB-concentrates in patients with terminal liver insufficiency. Anaesthesist. 1994;43:178–82.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Saner FH, Kirchner C. Monitoring and treatment of coagulation disorders in end-stage liver disease. Visc Med. 2016;32:241–8.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Solomon C, Pichlmaier U, Schoechl H, et al. Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth. 2010;104:555–62.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Tanaka KA, Bader SO, Gorlinger K. Novel approaches in management of perioperative coagulopathy. Curr Opin Anaesthesiol. 2014;27:72–80.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Poon KS, Chen CC, Thorat A, et al. Fibrinolysis after reperfusion of liver graft. Acta Anaesthesiol Taiwanica. 2015;53:41–3.CrossRefGoogle Scholar
  111. 111.
    Villa E, Cammà 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):1253–60.e1–4. Elsevier.PubMedCrossRefGoogle Scholar
  112. 112.
    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(1):75–82.PubMedCrossRefGoogle Scholar
  113. 113.
    Maruyama H, Takahashi M, Shimada T, Yokosuka O. Emergency anticoagulation treatment for cirrhosis patients with portal vein thrombosis and acute variceal bleeding. Scand J Gastroenterol. 2012;47(6):686–91.PubMedCrossRefGoogle Scholar
  114. 114.
    Hall TC, Garcea G, Metcalfe M, Bilk D, Rajesh A, Dennison A. Impact of anticoagulation on outcomes in acute non-cirrhotic and non- malignant portal vein thrombosis: a retrospective observational study. Hepato-Gastroenterology. 2013;60(122):311–7.PubMedGoogle Scholar
  115. 115.
    Beiderlinden M, Treschan TA, Görlinger K, Peters J. Argatroban anticoagulation in critically ill patients. Ann Pharmacother. 2007;41(5):749–54. SAGE Publications Sage CA: Los Angeles, CA.PubMedCrossRefGoogle Scholar
  116. 116.
    Doepker B, Mount KL, Ryder LJ, Gerlach AT, Murphy CV, Philips GS. Bleeding risk factors associated with argatroban therapy in the critically ill. J Thromb Thrombolysis. 2012;34(4):491–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital EssenEssenGermany

Personalised recommendations