Skip to main content
SpringerLink
Log in

Management of Severe Bleeding in Liver Disease and Transplantation

  • Chapter
  • First Online:
Point-of-Care Tests for Severe Hemorrhage

  • 1270 Accesses

Abstract

The concept that patients with cirrhosis are at increased risk of bleeding events is probably out of date. Liver failure is accompanied by multiple changes in the hemostatic system, because of reduced plasma levels of procoagulative and anticoagulative clotting factors synthesized by the intact liver. Thrombocytopenia is very frequent ranking first among the altered hematological tests but Von Willebrand factor is elevated and ADAMTS-13 instead decreased, counterbalancing/compensating in some way the thrombocytopenia. The hemostatic system is then in a delicate balance between prothrombotic and antithrombotic processes. Since the global effect of liver disease on the hemostatic system is complex, patients with end-stage liver disease (ESLD) can experience severe bleeding or, at the opposite, thrombotic complications. Conventional coagulation tests such as prothrombin time (PT) and international normalized ratio (INR) are not able to provide information on the actual coagulation status of the patient as well as to predict possible bleeding or thrombotic events in patients with liver disease. Standard hemostatic tests which are inadequate to evaluate the so-called rebalanced hemostatic profile of the cirrhotic patient may provide misleading information regarding the risk of bleeding: in particular, clinicians have to be aware that unneeded, useless, or even dangerous pro-hemostatic factors might be administered with no demonstrated benefit. Because of the limits of conventional coagulation tests, in recent years, the viscoelastic tests (Thromboelastography/thromboelastomatry) have gained increasing importance. A more dynamic and targeted approach to the overall hemostatic process is at the base of their success providing a visual information on fibrinolysis, on the presence of endogenous heparinoids and tendency to hypercoagulability: these characteristics make these tests ideal for a rapid diagnosis of the type of coagulopathy and for an appropriate choice of the therapeutic option in patients with acute or chronic liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lisman T, Leebeek FW, de Groot PG (2002) Haemostatic abnormalities in patients with liver disease. J Hepatol 37:280–287

    Article  CAS  PubMed  Google Scholar 

  2. Rapaport SI (2000) Coagulation problems in liver disease. Blood Coagul Fibrinolysis 11(Suppl 1):S69–S74

    Article  PubMed  Google Scholar 

  3. Tripodi A, Salerno F, Chantarangkul V et al (2005) Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 41:553–558

    Article  CAS  PubMed  Google Scholar 

  4. Lu SN, Wang JH, Liu SL et al (2006) Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma. Cancer 107:2212–2222

    Article  PubMed  Google Scholar 

  5. Qamar AA, Grace ND, Groszmann RJ et al (2009) Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis. Clin Gastroenterol Hepatol 7:689–695

    Article  PubMed Central  PubMed  Google Scholar 

  6. Ishikawa T, Ichida T, Matsuda Y et al (1998) Reduced expression of thrombopoietin is involved in thrombocytopenia in human and rat liver cirrhosis. J Gastroenterol Hepatol 13:907–913

    Article  CAS  PubMed  Google Scholar 

  7. Peck-Radosavljevic M, Wichlas M, Zacherl J et al (2000) Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production. Blood 95:795–801

    CAS  PubMed  Google Scholar 

  8. Aster RH (1966) Pooling of platelets in the spleen: role in the pathogenesis of "hypersplenic" thrombocytopenia. J Clin Invest 45:645–657

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Wang CS, Yao WJ, Wang ST, Chang TT, Chou P (2004) Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clin Infect Dis 39:790–796

    Article  PubMed  Google Scholar 

  10. Garcia-Suarez J, Burgaleta C, Hernanz N, Albarran F, Tobaruela P, Alvarez-Mon M (2000) HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy. Br J Haematol 110:98–103

    Article  CAS  PubMed  Google Scholar 

  11. Bleibel W, Caldwell SH, Curry MP, Northup PG (2013) Peripheral platelet count correlates with liver atrophy and predicts long-term mortality on the liver transplant waiting list. Transpl Int 26:435–442

    Article  CAS  PubMed  Google Scholar 

  12. Ordinas A, Escolar G, Cirera I et al (1996) Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions. Hepatology 24:1137–1142

    Article  CAS  PubMed  Google Scholar 

  13. Lisman T, Bongers TN, Adelmeijer J et al (2006) Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 44:53–61

    Article  CAS  PubMed  Google Scholar 

  14. Hollestelle MJ, Geertzen HG, Straatsburg IH, van Gulik TM, van Mourik JA (2004) Factor VIII expression in liver disease. Thromb Haemost 91:267–275

    CAS  PubMed  Google Scholar 

  15. Violi F, Leo R, Vezza E, Basili S, Cordova C, Balsano F (1994) Bleeding time in patients with cirrhosis: relation with degree of liver failure and clotting abnormalities. C.A.L.C. Group. Coagulation Abnormalities in Cirrhosis Study Group. J Hepatol 20:531–536

    Article  CAS  PubMed  Google Scholar 

  16. Amitrano L, Guardascione MA, Brancaccio V, Balzano A (2002) Coagulation disorders in liver disease. Semin Liver Dis 22:83–96

    Article  CAS  PubMed  Google Scholar 

  17. Lisman T, Leebeek FW, Mosnier LO et al (2001) Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 121:131–139

    Article  CAS  PubMed  Google Scholar 

  18. Huber K, Kirchheimer JC, Korninger C, Binder BR (1991) Hepatic synthesis and clearance of components of the fibrinolytic system in healthy volunteers and in patients with different stages of liver cirrhosis. Thromb Res 62:491–500

    Article  CAS  PubMed  Google Scholar 

  19. vanDeWater L, Carr JM, Aronson D, McDonagh J (1986) Analysis of elevated fibrin(ogen) degradation product levels in patients with liver disease. Blood 67:1468–1473

    CAS  PubMed  Google Scholar 

  20. Szczepanski M, Habior A, Szczepanik A, Soszka A, Grel K (1994) Thrombin clotting time and fibrin polymerization in liver cirrhosis. Mater Med Pol 26:87–90

    Article  CAS  PubMed  Google Scholar 

  21. Green G, Thomson JM, Dymock IW, Poller L (1976) Abnormal fibrin polymerization in liver disease. Br J Haematol 34:427–439

    Article  CAS  PubMed  Google Scholar 

  22. Rijken DC, Kock EL, Guimaraes AH et al (2012) Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests. J Thromb Haemost 10:2116–2122

    Article  CAS  PubMed  Google Scholar 

  23. Mammen EF (1994) Coagulopathies of liver disease. Clin Lab Med 14:769–780

    CAS  PubMed  Google Scholar 

  24. Escolar G, Cases A, Bastida E et al (1990) Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa. Blood 76:1336–1340

    CAS  PubMed  Google Scholar 

  25. Piccinino F, Sagnelli E, Pasquale G, Giusti G (1986) Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol 2:165–173

    Article  CAS  PubMed  Google Scholar 

  26. Lisman T, Caldwell SH, Burroughs AK et al (2010) Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol 53:362–371

    Article  PubMed  Google Scholar 

  27. Tripodi A, Mannucci PM (2007) Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J Hepatol 46:727–733

    Article  CAS  PubMed  Google Scholar 

  28. Giannini EG, Greco A, Marenco S, Andorno E, Valente U, Savarino V (2010) Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease. Clin Gastroenterol Hepatol 8:899–902

    Article  PubMed  Google Scholar 

  29. Sharma P, McDonald GB, Banaji M (1982) The risk of bleeding after percutaneous liver biopsy: relation to platelet count. J Clin Gastroenterol 4:451–453

    Article  CAS  PubMed  Google Scholar 

  30. Janssen HL (2000) Changing perspectives in portal vein thrombosis. Scand J Gastroenterol Suppl 232:69–73

    Google Scholar 

  31. Tripodi A, Primignani M, Mannucci PM (2010) Abnormalities of hemostasis and bleeding in chronic liver disease: the paradigm is challenged. Intern Emerg Med 5:7–12

    Article  PubMed  Google Scholar 

  32. Tripodi A, Primignani M, Chantarangkul V et al (2006) Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 44:440–445

    Article  CAS  PubMed  Google Scholar 

  33. Pache I, Bilodeau M (2005) Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther 21:525–529

    Article  CAS  PubMed  Google Scholar 

  34. Grabau CM, Crago SF, Hoff LK et al (2004) Performance standards for therapeutic abdominal paracentesis. Hepatology 40:484–488

    Article  PubMed  Google Scholar 

  35. Perdigao JP, de Almeida PC, Rocha TD et al (2012) Postoperative bleeding after dental extraction in liver pretransplant patients. J Oral Maxillofac Surg 70:e177–e184

    Article  PubMed  Google Scholar 

  36. Segal JB, Dzik WH (2005) Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 45:1413–1425

    Article  PubMed  Google Scholar 

  37. Fisher NC, Mutimer DJ (1999) Central venous cannulation in patients with liver disease and coagulopathy--a prospective audit. Intensive Care Med 25:481–485

    Article  CAS  PubMed  Google Scholar 

  38. Ewe K (1981) Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 26:388–393

    Article  CAS  PubMed  Google Scholar 

  39. Grant A, Neuberger J (1999) Guidelines on the use of liver biopsy in clinical practice. British Society of Gastroenterology. Gut 45(Suppl 4):IV1–IV11

    PubMed Central  PubMed  Google Scholar 

  40. Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A (1995) Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 36:437–441

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Blake JC, Sprengers D, Grech P, McCormick PA, McIntyre N, Burroughs AK (1990) Bleeding time in patients with hepatic cirrhosis. BMJ 301:12–15

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Suman A, Barnes DS, Zein NN, Levinthal GN, Connor JT, Carey WD (2004) Predicting outcome after cardiac surgery in patients with cirrhosis: a comparison of Child-Pugh and MELD scores. Clin Gastroenterol Hepatol 2:719–723

    Article  PubMed  Google Scholar 

  43. Farnsworth N, Fagan SP, Berger DH, Awad SS (2004) Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients. Am J Surg 188:580–583

    Article  PubMed  Google Scholar 

  44. de Goede B, Klitsie PJ, Lange JF, Metselaar HJ, Kazemier G (2012) Morbidity and mortality related to non-hepatic surgery in patients with liver cirrhosis: a systematic review. Best Pract Res Clin Gastroenterol 26:47–59

    Article  PubMed  Google Scholar 

  45. Shaikh AR, Muneer A (2009) Laparoscopic cholecystectomy in cirrhotic patients. JSLS 13:592–596

    Article  PubMed Central  PubMed  Google Scholar 

  46. Ikeda Y, Kanda T, Kosugi S et al (2009) Gastric cancer surgery for patients with liver cirrhosis. World J Gastrointest Surg 1:49–55

    Article  PubMed Central  PubMed  Google Scholar 

  47. Kao HK, Chang KP, Ching WC, Tsao CK, Cheng MH, Wei FC (2010) Postoperative morbidity and mortality of head and neck cancers in patients with liver cirrhosis undergoing surgical resection followed by microsurgical free tissue transfer. Ann Surg Oncol 17:536–543

    Article  PubMed  Google Scholar 

  48. Porte RJ (1993) Coagulation and fibrinolysis in orthotopic liver transplantation: current views and insights. Semin Thromb Hemost 19:191–196

    Article  CAS  PubMed  Google Scholar 

  49. Lu MS, Liu YH, Wu YC, Kao CL, Liu HP, Hsieh MJ (2005) Is it safe to perform esophagectomy in esophageal cancer patients combined with liver cirrhosis? Interact Cardiovasc Thorac Surg 4:423–425

    Article  PubMed  Google Scholar 

  50. Perkins L, Jeffries M, Patel T (2004) Utility of preoperative scores for predicting morbidity after cholecystectomy in patients with cirrhosis. Clin Gastroenterol Hepatol 2:1123–1128

    Article  PubMed  Google Scholar 

  51. Johnson PJ, Poon TC, Hjelm NM et al (1999) Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour. Br J Cancer 81:1188–1195

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Friedman LS (1999) The risk of surgery in patients with liver disease. Hepatology 29:1617–1623

    Article  CAS  PubMed  Google Scholar 

  53. Garrison RN, Cryer HM, Howard DA, Polk HC Jr (1984) Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg 199:648–655

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Chen CC, Hsu PW, Lee ST et al (2012) Brain surgery in patients with liver cirrhosis. J Neurosurg 117:348–353

    Article  PubMed  Google Scholar 

  55. An Y, Xiao YB, Zhong QJ (2007) Open-heart surgery in patients with liver cirrhosis: indications, risk factors, and clinical outcomes. Eur Surg Res 39:67–74

    Article  CAS  PubMed  Google Scholar 

  56. Murashita T, Komiya T, Tamura N et al (2009) Preoperative evaluation of patients with liver cirrhosis undergoing open heart surgery. Gen Thorac Cardiovasc Surg 57:293–297

    Article  PubMed  Google Scholar 

  57. Hayashida N, Shoujima T, Teshima H et al (2004) Clinical outcome after cardiac operations in patients with cirrhosis. Ann Thorac Surg 77:500–505

    Article  PubMed  Google Scholar 

  58. Tripodi A, Mannucci PM (2011) The coagulopathy of chronic liver disease. N Engl J Med 365:147–156

    Article  CAS  PubMed  Google Scholar 

  59. van Veen JJ, Spahn DR, Makris M (2011) Routine preoperative coagulation tests: an outdated practice? Br J Anaesth 106:1–3

    Article  PubMed  Google Scholar 

  60. Weeder PD, Porte RJ, Lisman T (2014) Hemostasis in liver disease: implications of new concepts for perioperative management. Transfus Med Rev 28:107–113

    Article  PubMed  Google Scholar 

  61. Lisman T, Porte RJ, Leebeek FW, Caldwell SH (2006) Methodological issues with coagulation testing in patients with liver disease. J Thromb Haemost 4:2061–2062

    Article  CAS  PubMed  Google Scholar 

  62. Tripodi A (2009) Tests of coagulation in liver disease. Clin Liver Dis 13:55–61

    Article  PubMed  Google Scholar 

  63. Lang T, von Depka M (2006) Possibilities and limitations of thrombelastometry/-graphy. Hamostaseologie 26:S20–S29

    CAS  PubMed  Google Scholar 

  64. Stravitz RT (2012) Potential applications of thromboelastography in patients with acute and chronic liver disease. Gastroenterol Hepatol (N Y) 8:513–520

    Google Scholar 

  65. Fenger-Eriksen C, Moore GW, Rangarajan S, Ingerslev J, Sorensen B (2010) Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders. Transfusion 50:2571–2576

    Article  PubMed  Google Scholar 

  66. Molinaro RJ, Szlam F, Levy JH, Fantz CR, Tanaka KA (2008) Low plasma fibrinogen levels with the Clauss method during anticoagulation with bivalirudin. Anesthesiology 109:160–161

    Article  PubMed  Google Scholar 

  67. Kang Y, Gaisor TA (1999) Hematologic considerations in the transplant patient. In: Sharpe MA, Gelb AW (eds) Anesthesia and Transplantation. Butterworth Heinemann, Boston, pp 363–387

    Google Scholar 

  68. Niemann CU, Eilers H (2010) Abdominal organ transplantation. Minerva Anestesiol 76:266–275

    CAS  PubMed  Google Scholar 

  69. Yost CS, Nieman CU (2010) Anesthesia for Organ transplantation. In: Miller RD (ed) Millers anaesthesia, 7th edn. Elsevier, Philadelphia 2155–2184

    Google Scholar 

  70. Hannaman MJ, Hevesi ZG (2011) Anesthesia care for liver transplantation. Transplant Rev (Orlando) 25:36–43

    Article  Google Scholar 

  71. Mitra B, Cameron PA, Gruen RL, Mori A, Fitzgerald M, Street A (2011) The definition of massive transfusion in trauma: a critical variable in examining evidence for resuscitation. Eur J Emerg Med 18:137–142

    Article  PubMed  Google Scholar 

  72. Sharpe JP, Weinberg JA, Magnotti LJ, Croce MA, Fabian TC (2012) Toward a better definition of massive transfusion: focus on the interval of hemorrhage control. J Trauma Acute Care Surg 73:1553–1557

    Article  PubMed  Google Scholar 

  73. Rossaint R, Bouillon B, Cerny V et al (2010) Management of bleeding following major trauma: an updated European guideline. Crit Care 14:R52

    Article  PubMed Central  PubMed  Google Scholar 

  74. Hoyt DB (2004) A clinical review of bleeding dilemmas in trauma. Semin Hematol 41:40–43

    Article  CAS  PubMed  Google Scholar 

  75. McCluskey SA, Karkouti K, Wijeysundera DN et al (2006) Derivation of a risk index for the prediction of massive blood transfusion in liver transplantation. Liver Transpl 12:1584–1593

    Article  PubMed  Google Scholar 

  76. Kashuk JL, Moore EE, Johnson JL et al (2008) Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? J Trauma 65:261–270; discussion 270–261

    Article  PubMed  Google Scholar 

  77. Reichert B, Kaltenborn A, Becker T, Schiffer M, Klempnauer J, Schrem H (2014) Massive blood transfusion after the first cut in liver transplantation predicts renal outcome and survival. Langenbecks Arch Surg 399:429–440

    Article  PubMed  Google Scholar 

  78. Feltracco P, Brezzi M, Barbieri S et al (2013) Blood loss, predictors of bleeding, transfusion practice and strategies of blood cell salvaging during liver transplantation. World J Hepatol 5:1–15

    Article  PubMed Central  PubMed  Google Scholar 

  79. de Boer MT, Molenaar IQ, Hendriks HG, Slooff MJ, Porte RJ (2005) Minimizing blood loss in liver transplantation: progress through research and evolution of techniques. Dig Surg 22:265–275

    Article  PubMed  Google Scholar 

  80. Massicotte L, Denault AY, Beaulieu D et al (2012) Transfusion rate for 500 consecutive liver transplantations: experience of one liver transplantation center. Transplantation 93:1276–1281

    Article  PubMed  Google Scholar 

  81. Massicotte L, Beaulieu D, Roy JD et al (2009) MELD score and blood product requirements during liver transplantation: no link. Transplantation 87:1689–1694

    Article  PubMed  Google Scholar 

  82. Cywinski JB, Alster JM, Miller C, Vogt DP, Parker BM (2014) Prediction of intraoperative transfusion requirements during orthotopic liver transplantation and the influence on postoperative patient survival. Anesth Analg 118:428–437

    Article  PubMed  Google Scholar 

  83. Martell M, Coll M, Ezkurdia N, Raurell I, Genesca J (2010) Physiopathology of splanchnic vasodilation in portal hypertension. World J Hepatol 2:208–220

    Article  PubMed Central  PubMed  Google Scholar 

  84. Saner FH, Gieseler RK, Akiz H, Canbay A, Gorlinger K (2013) Delicate balance of bleeding and thrombosis in end-stage liver disease and liver transplantation. Digestion 88:135–144

    Article  CAS  PubMed  Google Scholar 

  85. Tripodi A, Fracanzani AL, Primignani M et al (2014) Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol 61:148–154

    Article  CAS  PubMed  Google Scholar 

  86. Clevenger B, Mallett SV (2014) Transfusion and coagulation management in liver transplantation. World J Gastroenterol 20:6146–6158

    Article  PubMed Central  PubMed  Google Scholar 

  87. Cywes R, Packham MA, Tietze L et al (1993) Role of platelets in hepatic allograft preservation injury in the rat. Hepatology 18:635–647

    Article  CAS  PubMed  Google Scholar 

  88. Pereboom IT, Adelmeijer J, van Leeuwen Y, Hendriks HG, Porte RJ, Lisman T (2009) Development of a severe von Willebrand factor/ADAMTS13 dysbalance during orthotopic liver transplantation. Am J Transplant 9:1189–1196

    Article  CAS  PubMed  Google Scholar 

  89. Porte RJ, Bontempo FA, Knot EA, Lewis JH, Kang YG, Starzl TE (1989) Systemic effects of tissue plasminogen activator-associated fibrinolysis and its relation to thrombin generation in orthotopic liver transplantation. Transplantation 47:978–984

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Molenaar IQ, Warnaar N, Groen H, Tenvergert EM, Slooff MJ, Porte RJ (2007) Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 7:185–194

    Article  CAS  PubMed  Google Scholar 

  91. Senzolo M, Burra P, Cholongitas E, Burroughs AK (2006) New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol 12:7725–7736

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Bayly PJ, Thick M (1994) Reversal of post-reperfusion coagulopathy by protamine sulphate in orthotopic liver transplantation. Br J Anaesth 73:840–842

    Article  CAS  PubMed  Google Scholar 

  93. Agarwal S, Senzolo M, Melikian C, Burroughs A, Mallett SV (2008) The prevalence of a heparin-like effect shown on the thromboelastograph in patients undergoing liver transplantation. Liver Transpl 14:855–860

    Article  PubMed  Google Scholar 

  94. Findlay JY, Rettke SR (2000) Poor prediction of blood transfusion requirements in adult liver transplantations from preoperative variables. J Clin Anesth 12:319–323

    Article  CAS  PubMed  Google Scholar 

  95. Yeung MC, Tong SY, Tong PY, Cheung BH, Ng JY, Leung GK (2014) Use of viscoelastic haemostatic assay in emergency and elective surgery. Hong Kong Med J 21(1):45–51

    PubMed  Google Scholar 

  96. Mallett SV, Chowdary P, Burroughs AK (2013) Clinical utility of viscoelastic tests of coagulation in patients with liver disease. Liver Int 33:961–974

    Article  CAS  PubMed  Google Scholar 

  97. Alamo JM, Leon A, Mellado P et al (2013) Is "intra-operating room" thromboelastometry useful in liver transplantation? A case–control study in 303 patients. Transplant Proc 45:3637–3639

    Article  PubMed  Google Scholar 

  98. Gurusamy KS, Pissanou T, Pikhart H, Vaughan J, Burroughs AK, Davidson BR (2011) Methods to decrease blood loss and transfusion requirements for liver transplantation. Cochrane Database Syst 1:1–127

    Google Scholar 

  99. Wang SC, Shieh JF, Chang KY et al (2010) Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc 42:2590–2593

    Article  PubMed  Google Scholar 

  100. Kang YG, Martin DJ, Marquez J et al (1985) Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 64:888–896

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Gorlinger K (2006) Coagulation management during liver transplantation. Hamostaseologie 26:S64–S76

    CAS  PubMed  Google Scholar 

  102. Kozek-Langenecker SA, Afshari A, Albaladejo P et al (2013) Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 30:270–382

    Article  PubMed  Google Scholar 

  103. Peyrou V, Lormeau JC, Herault JP, Gaich C, Pfliegger AM, Herbert JM (1999) Contribution of erythrocytes to thrombin generation in whole blood. Thromb Haemost 81:400–406

    CAS  PubMed  Google Scholar 

  104. Thachil J (2011) Anemia--the overlooked factor in bleeding related to liver disease. J Hepatol 54:593–594, author reply 594–595

    Article  PubMed  Google Scholar 

  105. Villanueva C, Colomo A, Bosch A et al (2013) Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 368:11–21

    Article  CAS  PubMed  Google Scholar 

  106. Carson JL, Noveck H, Berlin JA, Gould SA (2002) Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion 42:812–818

    Article  PubMed  Google Scholar 

  107. Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A (2006) Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations. Liver Transpl 12:117–123

    Article  PubMed  Google Scholar 

  108. de Boer MT, Christensen MC, Asmussen M et al (2008) The impact of intraoperative transfusion of platelets and red blood cells on survival after liver transplantation. Anesth Analg 106:32–44, table of contents

    Article  PubMed  Google Scholar 

  109. Liu LL, Niemann CU (2011) Intraoperative management of liver transplant patients. Transplant Rev (Orlando) 25:124–129

    Article  Google Scholar 

  110. Massicotte L, Denault AY, Beaulieu D, Thibeault L, Hevesi Z, Roy A (2011) Aprotinin versus tranexamic acid during liver transplantation: impact on blood product requirements and survival. Transplantation 91:1273–1278

    Article  PubMed  Google Scholar 

  111. Kato M, Sugawara Y, Orii R et al (2001) Lactate levels in cirrhotic patients undergoing liver resection. Hepatogastroenterology 48:1106–1109

    CAS  PubMed  Google Scholar 

  112. Sarani B, Dunkman WJ, Dean L, Sonnad S, Rohrbach JI, Gracias VH (2008) Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection. Crit Care Med 36:1114–1118

    Article  PubMed  Google Scholar 

  113. Lisman T, Bakhtiari K, Pereboom IT, Hendriks HG, Meijers JC, Porte RJ (2010) Normal to increased thrombin generation in patients undergoing liver transplantation despite prolonged conventional coagulation tests. J Hepatol 52:355–361

    Article  CAS  PubMed  Google Scholar 

  114. Amarapurkar PD, Amarapurkar DN (2011) Management of coagulopathy in patients with decompensated liver cirrhosis. Int J Hepatol 2011:1–5

    Google Scholar 

  115. Gorlinger K, Fries D, Dirkmann D, Weber CF, Hanke AA, Schochl H (2012) Reduction of fresh frozen plasma requirements by perioperative point-of-care coagulation management with early calculated goal-directed therapy. Transfus Med Hemother 39:104–113

    Article  PubMed Central  PubMed  Google Scholar 

  116. Al Dieri R, Peyvandi F, Santagostino E et al (2002) The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding. Thromb Haemost 88:576–582

    PubMed  Google Scholar 

  117. Chowdary P, Saayman AG, Paulus U, Findlay GP, Collins PW (2004) Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 125:69–73

    Article  PubMed  Google Scholar 

  118. Ganter MT, Hofer CK (2008) Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 106:1366–1375

    Article  PubMed  Google Scholar 

  119. Noval-Padillo JA, Leon-Justel A, Mellado-Miras P et al (2010) Introduction of fibrinogen in the treatment of hemostatic disorders during orthotopic liver transplantation: implications in the use of allogenic blood. Transplant Proc 42:2973–2974

    Article  CAS  PubMed  Google Scholar 

  120. Wang SC, Lin HT, Chang KY et al (2010) Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery. Liver Transpl 18:1254–1258

    Google Scholar 

  121. Larsen OH, Fenger-Eriksen C, Christiansen K, Ingerslev J, Sorensen B (2011) Diagnostic performance and therapeutic consequence of thromboelastometry activated by kaolin versus a panel of specific reagents. Anesthesiology 115:294–302

    Article  CAS  PubMed  Google Scholar 

  122. Roche AM, James MF, Grocott MP, Mythen MG (2003) Citrated blood does not reliably reflect fresh whole blood coagulability in trials of in vitro hemodilution. Anesth Analg 96:58–61, table of contents

    CAS  PubMed  Google Scholar 

  123. Zambruni A, Thalheimer U, Leandro G, Perry D, Burroughs AK (2004) Thromboelastography with citrated blood: comparability with native blood, stability of citrate storage and effect of repeated sampling. Blood Coagul Fibrinolysis 15:103–107

    Article  CAS  PubMed  Google Scholar 

  124. Hardisty RM, Hutton RA (1965) The kaolin clotting time of platelet-rich plasma: a test of platelet factor-3 availability. Br J Haematol 11:258–268

    Article  CAS  PubMed  Google Scholar 

  125. Durila M (2011) Kaolin activated thromboelastography can result in false positive fibrinolytic trace. Anaesth Intensive Care 39:775–776

    CAS  PubMed  Google Scholar 

  126. Kirchner C, Dirkmann D, Treckmann JW et al (2014) Coagulation management with factor concentrates in liver transplantation: a single-center experience. Transfusion 54((10 Pt 2)):2760–2768

    Article  PubMed  Google Scholar 

  127. Ranucci M, Baryshnikova E, Crapelli GB et al (2015) Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc 4(6). pii: e002066. doi:10.1161/JAHA.115.002066

  128. Gorlinger K, Dirkmann D, Hanke AA et al (2011) First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. Anesthesiology 115:1179–1191

    PubMed  Google Scholar 

  129. Dalmau A, Sabate A, Aparicio I (2009) Hemostasis and coagulation monitoring and management during liver transplantation. Curr Opin Organ Transplant 14:286–290

    Article  PubMed  Google Scholar 

  130. Hanke AA, Joch C, Gorlinger K (2013) Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study. Br J Anaesth 110:764–772

    Article  CAS  PubMed  Google Scholar 

  131. Schochl H, Nienaber U, Hofer G et al (2010) Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 14:R55

    Article  PubMed Central  PubMed  Google Scholar 

  132. Fenger-Eriksen C, Tonnesen E, Ingerslev J, Sorensen B (2009) Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy. J Thromb Haemost 7:1099–1105

    Article  CAS  PubMed  Google Scholar 

  133. Caldwell SH, Sanyal AJ (2009) Coagulation disorders and bleeding in liver disease: future directions. Clin Liver Dis 13:155–157

    Article  PubMed  Google Scholar 

  134. Tripodi A, Primignani M, Chantarangkul V et al (2009) The coagulopathy of cirrhosis assessed by thromboelastometry and its correlation with conventional coagulation parameters. Thromb Res 124:132–136

    Article  CAS  PubMed  Google Scholar 

  135. Hiippala ST, Myllyla GJ, Vahtera EM (1995) Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 81:360–365

    CAS  PubMed  Google Scholar 

  136. Sorensen B, Bevan D (2010) A critical evaluation of cryoprecipitate for replacement of fibrinogen. Br J Haematol 149:834–843

    Article  CAS  PubMed  Google Scholar 

  137. TEG 5000 User Manual. Niles IH (1999–2007). 178–180

    Google Scholar 

  138. Jeger V1, Willi S, Liu T et al (2012) The Rapid TEG α-Angle may be a sensitive predictor of transfusion in moderately injured blunt trauma patients. Scientific World Journal 2012:821794. doi:10.1100/2012/821794. Epub 2012 Apr 1

    Google Scholar 

  139. Yang Lu S, Tanaka KA, Abuelkasem E, Planinsic RM, Sakai T (2014) Clinical applicability of rapid thrombelastography and functional fibrinogen thrombelastography to adult liver transplantation. Liver Transpl 20:1097–1105

    Article  PubMed  Google Scholar 

  140. Agren A, Wikman AT, Ostlund A, Edgren G (2014) TEG(R) functional fibrinogen analysis may overestimate fibrinogen levels. Anesth Analg 118:933–935

    Article  CAS  PubMed  Google Scholar 

  141. Pereboom IT, de Boer MT, Haagsma EB, Hendriks HG, Lisman T, Porte RJ (2009) Platelet transfusion during liver transplantation is associated with increased postoperative mortality due to acute lung injury. Anesth Analg 108:1083–1091

    Article  PubMed  Google Scholar 

  142. Seo H, Choi JH, Moon YJ, Jeong SM (2015) FIBTEM of thromboelastometry does not accurately represent fibrinogen concentration in patients with severe hypofibrinogenemia during liver transplantation. Ann Transplant 20:342–350

    Article  PubMed  Google Scholar 

  143. Roullet S, Freyburger G, Cruc M et al (2015) Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry-based algorithm. Liver Transpl 21:169–179

    Article  PubMed  Google Scholar 

  144. Wikkelso A, Lunde J, Johansen M et al (2013) Fibrinogen concentrate in bleeding patients. Cochrane Database Syst

    Google Scholar 

  145. Coakley M, Reddy K, Mackie I, Mallett S (2006) Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests. J Cardiothorac Vasc Anesth 20(4):548–553

    Google Scholar 

  146. Henry DA, Carless PA, Moxey AJ et al (2011) Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst

    Google Scholar 

  147. Makwana J, Paranjape S, Goswami J (2010) Antifibrinolytics in liver surgery. Indian J Anaesth 54(6):489–495

    Google Scholar 

  148. Ferro D, Celestini A, Violi F (2009) Hyperfibrinolysis in liver disease. Clin Liver Dis 13:21–31

    Google Scholar 

  149. Warnaar N, Mallett SV, de Boer MT et al (2007) The impact of aprotinin on renal function after liver transplantation: an analysis of 1,043 patients. Am J Transplant 7:2378–2387

    Article  CAS  PubMed  Google Scholar 

  150. Trzebicki J, Flakiewicz E, Kosieradzki M et al (2010) The use of thromboelastometry in the assessment of hemostasis during orthotopic liver transplantation reduces the demand for blood products. Ann Transplant 15:19–24

    PubMed  Google Scholar 

  151. Groenland TH, Porte RJ (2006) Antifibrinolytics in liver transplantation. Int Anesthesiol Clin 44:83–97

    Article  PubMed  Google Scholar 

  152. Kang Y (1995) Thromboelastography in liver transplantation. Semin Thromb Hemost 21(Suppl 4):34–44

    PubMed  Google Scholar 

  153. Lodge JP, Jonas S, Jones RM et al (2005) Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl 11:973–979

    Article  PubMed  Google Scholar 

  154. Planinsic RM, van der Meer J, Testa G et al (2005) Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transpl 11:895–900

    Article  PubMed  Google Scholar 

  155. Scheffert JL, Taber DJ, Pilch NA, McGillicuddy JW, Baliga PK, Chavin KD (2013) Timing of factor VIIa in liver transplantation impacts cost and clinical outcomes. Pharmacotherapy 33:483–488

    Article  CAS  PubMed  Google Scholar 

  156. Yank V, Tuohy CV, Logan AC et al (2011) Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med 154:529–540

    Article  PubMed Central  PubMed  Google Scholar 

  157. Mannucci PM (1997) Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 90:2515–2521

    CAS  PubMed  Google Scholar 

  158. Arshad F, Stoof SC, Leebeek FW et al (2015) Infusion of DDAVP does not improve primary hemostasis in patients with cirrhosis. Liver Int 35:1809–1815

    Article  CAS  PubMed  Google Scholar 

  159. Agnelli G, Parise P, Levi M, Cosmi B, Nenci GG (1995) Effects of desmopressin on hemostasis in patients with liver cirrhosis. Haemostasis 25:241–247

    CAS  PubMed  Google Scholar 

  160. Pivalizza EG, Warters RD, Gebhard R (2003) Desmopressin before liver transplantation. Can J Anaesth 50:748–749

    Article  PubMed  Google Scholar 

  161. Wong AY, Irwin MG, Hui TW, Fung SK, Fan ST, Ma ES (2003) Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy. Can J Anaesth 50:14–20

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Anaesthesiology and Intensive Care Unit, Azienda Ospedaliero-Universitaria di Modena-Policlinico, Modena, Italy

    Lesley De Pietri MD

  2. 2nd Service Anesthesia Critical Care Medicine, Ospedale Niguarda Ca’ Granda, Milan, Italy

    Andrea De Gasperi MD

  3. Department of Medicine, Anesthesia and Intensive Care Unit, Padova University Hospital, Padova, Italy

    Paolo Feltracco MD

  4. Liver Transplant Anaesthesia and Critical Care, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

    Gianni Biancofiore MD

  5. Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy

    Marco Senzolo MD

  6. Department of Medicine, 5th Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

    David Sacerdoti MD, PhD

Authors
  1. Lesley De Pietri MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea De Gasperi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo Feltracco MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gianni Biancofiore MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marco Senzolo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Sacerdoti MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lesley De Pietri MD .

Editor information

Editors and Affiliations

  1. Department of Anaesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Italy

    Marco Ranucci

  2. Department of Medicine Hemorrhagic and Thrombotic Diseases Unit, University of Padua Medical School, Padua, Italy

    Paolo Simioni

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

De Pietri, L., De Gasperi, A., Feltracco, P., Biancofiore, G., Senzolo, M., Sacerdoti, D. (2016). Management of Severe Bleeding in Liver Disease and Transplantation. In: Ranucci, M., Simioni, P. (eds) Point-of-Care Tests for Severe Hemorrhage. Springer, Cham. https://doi.org/10.1007/978-3-319-24795-3_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-24795-3_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-24793-9

  • Online ISBN: 978-3-319-24795-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation