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Gastroenterologie up2date 2016; 12(01): 75-88
DOI: 10.1055/s-0042-103062
Leber/Galle/Pankreas
© Georg Thieme Verlag KG Stuttgart · New York

Leber und Gerinnung

Omar Mohamed
,
Matthias Dollinger
,
Thomas Seufferlein
,
Martin Griesshammer
Further Information

Publication History

Publication Date:
18 March 2016 (online)

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Kernaussagen

Pathophysiologie

  • Aktuelle und moderne Betrachtungen des Gerinnungssystems bieten neue Einblicke in die hämostatischen Veränderungen bei akuten und chronischen Lebererkrankungen.

  • Bei Lebererkrankungen kommt es nicht nur zu einer Reduktion prokoagulatorischer Gerinnungsfaktoren, sondern auch zu Veränderungen im antikoagulatorischen, fibrinolytischen und antifibrinolytischen System. So entsteht oft ein fragiles, aber bilanziertes Hämostasegleichgewicht.

  • Zusätzliche Ereignisse wie Infektionen, Nierenversagen, Entzündungen und Trauma können dieses System in Richtung von Blutungs- oder Thrombosekomplikationen kippen lassen.

Diagnostik und Therapie

  • Screening-Gerinnungstests wie Quick/INR sind ungenau und möglicherweise irreführend bei der fortgeschrittenen Lebererkrankung. Die prophylaktische Verwendung von Frischplasma basierend auf INR-Cut-offs wird daher nicht empfohlen.

  • Alternative In-vitro-Tests, wie das endogene Thrombinpotenzial (ETP) und die Thrombelastografie (TEG), sind nicht ausreichend validiert, um als Ersatz empfohlen zu werden.

  • Prophylaxen und Rescue-Therapie von Blutungskomplikationen bleiben momentan empirisch und sollten individualisiert werden. Der Fokus auf eine schnelle Behandlung von Infektionen, Nierenversagen und Volumenüberlastung wird durch vorhandene Studiendaten unterstützt.

  • Antifibrinolytika spielen bei Patienten mit Lebererkrankungen und Hyperfibrinolyse eine Rolle. Der „Off-Label“-Gebrauch von hämostatischen Produkten wie rFVIIa und PCC ist ungenügend validiert, kostspielig und birgt potenzielle thrombotische Risiken.

  • Patienten mit fortgeschrittener Lebererkrankung können trotz erniedrigter Gerinnungsfaktoren auch thromboembolische Komplikationen, typischerweise eine Pfortaderthrombose, entwickeln. In diesen Situationen ist das Nutzen-Risiko-Verhältnis einer Antikoagulation durch Studiendaten nicht hinreichend geklärt. Es gibt daher einen großen Bedarf an klinischer Forschung, um diese Wissenslücken zukünftig durch Studien zu schließen.

 

  • Literatur

  • 1 Mannucci PM. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related?. No. J Thromb Haemost 2006; 4: 721-723
    PubMedSearch in Google Scholar
  • 2 Lisman T, Leebeek FW, Mosnier LO et al. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 2001; 121: 131-139
    CrossrefPubMedSearch in Google Scholar
  • 3 Lisman T, Leebeek FWG, De Groot PG. Haemostatic abnormalities in patients with liver disease. J Hepatol 2002; 37: 280-287
    CrossrefPubMedSearch in Google Scholar
  • 4 Sharara AI, Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med 2001; 345: 669-681
    CrossrefPubMedSearch in Google Scholar
  • 5 De Boer MT, Molenaar IQ, Hendriks HG et al. Minimizing blood loss in liver transplantation: progress through research and evolution of techniques. Dig Surg 2005; 22: 265-275
    CrossrefPubMedSearch in Google Scholar
  • 6 Massicotte L, Lenis S, Thibeault L et al. Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations. Liver Transpl 2006; 12: 117-123
    CrossrefPubMedSearch in Google Scholar
  • 7 Hadem J, Tacke F, Bruns T et al. Acute Liver Failure Study Group Germany. Etiologies and outcomes of acute liver failure in Germany. Clin Gastroenterol Hepatol 2012; 10: 664-669
    CrossrefPubMedSearch in Google Scholar
  • 8 O’Grady JG, Alexander GJ, Hayllar KM et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439-445
    CrossrefPubMedSearch in Google Scholar
  • 9 Munoz SJ, Rajender Reddy K et al. The coagulopathy of acute liver failure and implications for intracranial pressure monitoring. Neurocrit Care 2008; 9: 103-107
    CrossrefPubMedSearch in Google Scholar
  • 10 Kerr R, Newsome P, Germain L et al. Effects of acute liver injury on blood coagulation. J Thromb Haemost 2003; 1: 754-759
    CrossrefPubMedSearch in Google Scholar
  • 11 Pernambuco JR, Langley PG, Hughes RD et al. Activation of the fibrinolytic system in patients with fulminant liver failure. Hepatology 1993; 18: 1350-1356
    CrossrefPubMedSearch in Google Scholar
  • 12 Elinav E, Ben-Dov I, Hai-Am E et al. The predictive value of admission and follow up factor V and VII levels in patients with acute hepatitis and coagulopathy. J Hepatol 2005; 42: 82-86
    PubMedSearch in Google Scholar
  • 13 Trotter JF. Practical management of acute liver failure in the Intensive Care Unit. Curr Opin Crit Care 2009; 15: 163-167
    CrossrefPubMedSearch in Google Scholar
  • 14 Stravitz RT, Kramer AH, Davern T et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med 2007; 35: 2498-2508
    CrossrefPubMedSearch in Google Scholar
  • 15 Stravitz RT, Lisman T, Luketic VA et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012; 56: 129-136
    CrossrefPubMedSearch in Google Scholar
  • 16 Larsen FS, Schmidt LE, Bernsmeier C et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 2016; 64: 69-78
    CrossrefPubMedSearch in Google Scholar
  • 17 Bashour FN, Teran JC, Mullen KD. Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol 2000; 95: 2936-2939
    CrossrefPubMedSearch in Google Scholar
  • 18 Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of „hypersplenic” thrombocytopenia. J Clin Invest 1966; 45: 645-657
    CrossrefPubMedSearch in Google Scholar
  • 19 Ramos-Casals M, García-Carrasco M, López-Medrano F et al. Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. Medicine (Baltimore) 2003; 82: 87-96
    CrossrefPubMedSearch in Google Scholar
  • 20 Peck-Radosavljevic M, Wichlas M, Zacherl J et al. Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production. Blood 2000; 95: 795-801
    PubMedSearch in Google Scholar
  • 21 Tripodi A, Primignani M, Chantarangkul V et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44: 440-445
    CrossrefPubMedSearch in Google Scholar
  • 22 Ben-Ari Z, Panagou M, Patch D et al. Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography. J Hepatol 1997; 26: 554-559
    CrossrefPubMedSearch in Google Scholar
  • 23 Colucci M, Binetti BM, Branca MG et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 2003; 38: 230-237
    PubMedSearch in Google Scholar
  • 24 Roberts LN, Patel RK, Arya R. Haemostasis and thrombosis in liver disease. Br J Haematol 2010; 148: 507-521
    CrossrefPubMedSearch in Google Scholar
  • 25 Boks AL, Brommer EJ, Schalm SW et al. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage. Hepatology 1986; 6: 79-86
    CrossrefPubMedSearch in Google Scholar
  • 26 Hu KQ, Yu AS, Tiyyagura L et al. Hyperfibrinolytic activity in hospitalized cirrhotic patients in a referral liver unit. Am J Gastroenterol 2001; 96: 1581-1586
    CrossrefPubMedSearch in Google Scholar
  • 27 Di Minno G, Martinez J, McKean ML et al. Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis. Am J Med 1985; 79: 552-559
    CrossrefPubMedSearch in Google Scholar
  • 28 Seeff LB, Everson GT, Morgan TR 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: 877-883
    CrossrefPubMedSearch in Google Scholar
  • 29 Bonnard P, Vitte RL, Barbare JC et al. Is bleeding time measurement useful for choosing the liver biopsy route? The results of a pragmatic, prospective multicentric study in 219 patients. J Clin Gastroenterol 1999; 29: 347-349
    CrossrefPubMedSearch in Google Scholar
  • 30 Bedreli S, Sowa JP, Gerken G et al. Management of acute-on-chronic liver failure: rotational thromboelastometry may reduce substitution of coagulation factors in liver cirrhosis. Gut 2016; 65: 357-358
    CrossrefPubMedSearch in Google Scholar
  • 31 Bienholz A, Canbay A, Saner FH. Coagulation management in patients with liver disease. Med Klin Intensivmed Notfmed 2015; (Epub ahead of print)
    PubMedSearch in Google Scholar
  • 32 Lorenz R, Kienast J, Otto U et al. Efficacy and safety of a prothrombin complex concentrate with two virus-inactivation steps in patients with severe liver damage. Eur J Gastroenterol Hepatol 2003; 15: 15-20
    CrossrefPubMedSearch in Google Scholar
  • 33 Stanca CM, Montazem AH, Lawal A et al. Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial. J Oral Maxillofac Surg 2010; 68: 138-143
    CrossrefPubMedSearch in Google Scholar
  • 34 de Franchis R, Arcidiacono PG, Carpinelli L et al. Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: a multicenter, double-blind study. New Italian Endoscopic Club. Hepatology 1993; 18: 1102-1107
    CrossrefPubMedSearch in Google Scholar
  • 35 Wong AY, Irwin MG, Hui TW et al. Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy. Can J Anaesth 2003; 50: 14-20
    CrossrefPubMedSearch in Google Scholar
  • 36 Molenaar IQ, Warnaar N, Groen H et al. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2007; 7: 185-194
    CrossrefPubMedSearch in Google Scholar
  • 37 Gunawan B, Runyon B. The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis. Aliment Pharmacol Ther 2006; 23: 115-120
    CrossrefPubMedSearch in Google Scholar
  • 38 Levi M, Levy JH, Andersen HF et al. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010; 363: 1791-1800
    CrossrefPubMedSearch in Google Scholar
  • 39 McHutchison JG, Dusheiko G, Shiffman ML et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007; 357: 2227-2236
    CrossrefPubMedSearch in Google Scholar
  • 40 Afdhal N, Giannini E, Tayyab GN et al. Eltrombopag in chronic liver disease patients with thrombocytopenia undergoing an elective invasvie procedure: results from ELEVATE, a randomised clinical trial. J Hepatol 2010; 52: S460
    PubMedSearch in Google Scholar