Coagulation management during liver transplantation

Summary

In the course of liver transplantation many patients develop coagulation and bleeding disorders. On the other hand, some patients suffer thromboembolic events in the perioperative period with sometimes fatal outcome. For this reason, in 1999 we changed our coagulation management for liver transplantation and abolished the routine prophylaxis with antifibrinolytic drugs. In this context we implemented the ROTEM^® system (Pentapharm GmbH, Munich) in our perioperative point-of-care coagulation management.

From 2000 to 2005, we analysed more than 18.000 ROTEM^® measurements in the context of 642 liver transplantations. Prophylactic administration of antifibrinolytic drugs was only done in patients with fulminant liver failure or if MCF in ExTEM ≤35 mm at the beginning of surgery. In the other patients hyperfibrinolysis could be detected in 60% during the operation. However, therapy with an antifibrinolytic drug was only necessary in 40% of the patients. Our experience with ROTEM^® analysis was summarised in an algorithm for ROTEM^® based perioperative coagulation management for liver transplantation.

Keywords

Liver transplantation - LTX - point-of-care coagulation management - thrombelastometry - hyperfibrinolysis

• References

• 1 Aarts PA, van den Broek SA, Prins GW. et al. Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. Arteriosclerosis 1998; 8: 819-824.
• 2 Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and aquired factor VIII or IX inhibitors. J Thromb Haemost 2004; 2: 2078-2079.
• 3 Apsner R, Schwarzenhofer M, Derfler K. et al. Impairment of citrate metabolism in acute hepatic failure. Wien Klin Wochenschr 1997; 109: 123-127.
• 4 Baubillier E, Cherqui D, Dominique C. et al. A fatal thrombotic complication during liver transplantation after aprotinin administration. Transplantation 1994; 57: 1664-1666.
• 5 Beek H, Hellstern P. In vitro characterization of solvent/detergent-treated human plasma and of quarantine fresh frozen plasma. Vox Sang 1998; 74: 219-223.
• 6 Bechstein WO, Neuhaus P. Blutungsproblematik in der Leberchirurgie und Lebertransplantation. Chirurg 2000; 71: 363-368.
• 7 Budde U, Schneppenheim R. Von Willebrand factor and von Willebrand disease. Rev Clin Exp Hematol 2001; 5: 335-368.
• 8 Calatzis A, Heesen M, Spannagl M. Patientennahe Sofortdiagnostik von Hämostasestörungen in der Anästhesie und Intensivmedizin. Anaesthesist 2003; 52: 229-237.
• 9 Centers for Disease Control and Prevention.. Fatal bacterial infections associated with platelet transfusions – United States, 2004. MMWR 2005; 54: 168-170.
• 10 Chowdhury P, Saayman AG, Paulus U. et al. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 2004; 125: 59-73.
• 11 Cosgriff N, Moore EE, Sauaia A. et al. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidosis revisited. J Trauma 1997; 42: 857-861.
• 12 Danks RR. Triangle of death. How hypothermia, acidosis & coagulopathy can adversely impact trauma patients. JEMS 2002; 27: 61-6 68-70.
• 13 De Jonge J, Groenland TH, Metselaar HJ. et al. Fibrinolysis during liver transplantation is enhanced by using solvent/deter-gent virus-inactivated plasma (ESDEP). AnesthAnalg 2002; 94: 1127-1131.
• 14 DRK-Blutspendedienst West gGmbH.. Humanes S/D-Plasma, lyophilisiert – Das virusinaktivierte Humanplasma der DRK-Blutspendedienst West gGmbH. Hämotherapie 2004; 2.
• 15 Dusel CH, Grundmann C, Eich S. et al. Identification of prothrombin as a major thrombogenic agent in prothrombin complex concentrates. Blood Coagul Fibrinol 2004; 15: 405-411.
• 16 Engstrom M, Reinstrup P, Schott U. An in vitro evaluation of standard rotational thrombelastography in monitoring of effects of recombinant factor VIIa on coagulopathy induced by hydroxy ethyl starch. BMC Blood Disord 2005; 5: 3.
• 17 Ferrara A, MacArthur JD, Wright HK. et al. Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion. Am J Surg 1990; 160: 515-518.
• 18 Findlay JY, Rettke SR, Ereth MH. et al. Aprotinin reduces blood cell transfusion in orthothopic liver transplantation: a prospective, randomized, double-blind study. Liver Transpl 2001; 7: 808-810.
• 19 Fitzsimons MG, Peterfreund RA, Raines DE. Aprotinin administration and pulmonary thromboembolism during orthotopic liver transplantation: report of two cases. Anesth Analg 2001; 92: 1418-1421.
• 20 Fries D, Innerhofer P, Reif C. et al. The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in vitro model. Anesth Analg 2006; 102: 347-351.
• 21 Fries D, Steif W, Haas T. et al. Die Dilutionskoagulopathie, ein unterschätztes Problem?. AINS 2004; 39: 745-750.
• 22 Gali B, Rettke SR, Plevak DJ. et al. The effect of in vitro recombinant factor VIIa on coagulation parameters for blood taken during liver transplantation. Transplant Proc 2005; 37: 4367-4369.
• 23 Görlinger K. ROTEM – Erweitertes perioperatives Gerinnungsmanagement. J Anästh Intensivbeh 2005; 12: 53-58.
• 24 Görlinger K, Dirkmann D, Kiss G. et al. ROTEMbased management for diagnosis and treatment of acute haemorrhage during liver transplantation. Poster Presentation, Euroanaesthesia 2006, Madrid 3–6 June 2006.
• 25 Gosseye S, van Obbergh L, Weynand B. et al. Platelet aggregates in small lung vessels and death during liver transplantation. Lancet 1991; 338: 532-534.
• 26 Haas T, Innerhofer P, Kuhbacher G. et al. Successful reversal of deleterious coagulopathy by recombinant factor VIIa. Anesth Analg 2005; 100: 54-58.
• 27 Harding SA, Mallett SV, Peachey TD. et al. Use of heparinase modified thrombelastography in liver transplantation. Br J Anaesth 1997; 78: 175-179.
• 28 Hellstern P. Solvent/detergent-treated plasma: composition, efficacy, and safety. Curr Opin Hematol 2004; 11: 346-350.
• 29 Hendriks HG, Meijer K, de Wolf JT. et al. Reduced transfusion requirement by recombinant factor VIIa in orthotopic liver transplantation: a pilot study. Transplantation 2001; 71: 402-405.
• 30 Heptinstall S, Johnson A, Glenn JR. et al. Adenine nucleotide metabolism in human blood – important roles for leukocytes and erythrocytes. J Thromb Haemost 2005; 2331-2339.
• 31 Hiippala ST. Dextran and hydroxyethyl starch interfere with fibrinogen assays. Blood Coagul Fibrinol 1995; 6: 743-746.
• 32 Hiippala ST, Myllyla GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg 1995; 81: 360-365.
• 33 Hoffman M, Monroe 3rd DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-965.
• 34 Ingerslev J, Christiansen K, Calatzis A. et al. Management and moitoring of recombinant activated factor VII. Blood Coagul Fibrinol 2000; 11 (Suppl. 01) S25-S30.
• 35 Innerhofer P, Streif W, Kühbacher G. et al. Monitoring der perioperativen Dilutionskoagulopathie mittels ROTEM-Analyzer – Grundlagen und klinische Beispiele. AINS 2004; 39: 739-744.
• 36 Jordan A, David T, Homer-Vanniasinkam S. et al. The effects of margination and red cell augmented platelet diffusivity on platelet adhesion in complex flow. Biorheology 2004; 41: 641-653.
• 37 Jurkovich GJ, Greiser WB, Luterman A. et al. Hypothermia in trauma victims: an ominous predictor of survival. J Trauma 1987; 1019-1024.
• 38 Karkouti K, Beattie WS, Dattilo KM. et al. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006; 46: 327-338.
• 39 Kenet G, Walden R, Eldad A. et al. Treatment of traumatic bleeding with recombinant factor VIIa. Lancet 1999; 354: 1879.
• 40 Kettner SC, Gonano C, Seebach F. et al. Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation. AnesthAnalg 1998; 86: 691-695.
• 41 Koscielny J, Ziemer S, Radtke H. et al. A practical concept for preoperative identification of patients with impaired primary hemostasis. Clin Appl Thromb Hemost 2004; 10: 195-204.
• 42 Kost GJ, Jammal MA, Ward RE. et al. Monitoring of ionized calcium during human hepatic transplantation. Critical values and their revalance to cardiac and hemodynamic management. Am J Clin Pathol 1986; 86: 61-70.
• 43 Kramer L, Bauer E, Joukhadar C. et al. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med 2003; 31: 2450-2455.
• 44 Lang T, Toller W, Gutl M. et al. Different effects of abciximab and cytochalasin D on clot strength in thrombelastography. J Thromb Haemost 2004; 2: 147-153.
• 45 Lentschener C, Roche K, Ozier Y. A review in orthotopic liver transplantation: can ist harmful effects offset ist beneficial effects?. Anesth Analg 2005; 100: 1248-1255.
• 46 Llamas P, Cabrera R, Gomez-Arnau J. et al. Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin. Haematologica 1998; 83: 338-346.
• 47 Lodge JP, Jonas S, Jones RM. et al. rFVIIa OLT Study Group. Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver Transplantation. LiverTranspl 2005; 11: 872-874.
• 48 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: 1-6.
• 49 Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354: 353-365.
• 50 Marquez J, Martin D, Virji MA. et al. Cardiovascular depression secondary to ionic hypocalcemia during hepatic transplantation in humans. Anesthesiology 1986; 65: 457-461.
• 51 Martini WZ, Pusateri AE, Uscilowicz JM. et al. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J Trauma 2005; 58: 1009-1010.
• 52 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.
• 53 McCrath DJ, Cerboni E, Frumento RJ. et al. Thrombelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 2005; 100: 1576-1583.
• 54 McLoughlin TM, Fontana JL, Alving B. et al. Profound normovolemic hemodilution: hemostatic effects in patients and in a porcine model. Anesth Analg 1996; 83: 459-465.
• 55 Meng ZH, Wolberg AS, Monroe 3rd DM. et al. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of highdose factor VIIa in hypothermic and acidotic patients. J Trauma 2003; 55: 886-891.
• 56 Menitove JE. (ed). America’s Blood Centers. Detection of bacterial contamination in platelet components. Blood Bulletin 2003; 6: 4.
• 57 Mikhail J. The trauma triad of death: hypotherma, acidosis, and coagulopathy. AACN Clin Issues 1999; 10: 85-94.
• 58 Mittermayr M, Margreiter J, Velik-Salchner C. et al. Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem): an in vitro study. Br J Anaesth 2005; 95: 310-316.
• 59 Molenaar IQ, Begliomini B, Grazi GL. et al EMSALT Study Group.. The effect of aprotinin on renal function in orthotopic liver transplantation. Transplantation 2001; 71: 247-252.
• 60 Morrow JF, Braine HG, Kickler TS. et al. Septic reactions to platelet transfusions. A persistent problem. JAMA 1991; 266: 555-558.
• 61 Ness P, Braine H, King K. et al. Single-donor platelets reduce the risk of septic platelet transfusion reactions. Transfusion 2002; 41: 857-861.
• 62 Nielsen VG. Effects of aprotinin on plasma coagulation kinetics determined by thrombelastography: role of factor XI. Acta Anaesthesiol Scand 2006; 50: 168-172.
• 63 Pietsch UC, Schaffranietz L. Anästhesiologisches Vorgehen bei orthotopen Lebertransplantationen (LTX) – Ergebnisse einer Umfrage. AINS 2006; 41: 21-26.
• 64 Pihusch R, Rank A, Gohring P. et al. Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease. J Hepatol 2002; 37: 548-555.
• 65 Planinsic RM, van der Meer J, Testa G. et al. Safty and eficacy of a single bouls administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transpl 2005; 11: 872-874.
• 66 Poon MC, d’Oiron R. Recombinant activated factor VII (NovoSeven) treatment of platelet-related bleeding disorders. International registry on recombinant factor VIIa and congenital platelet disorders group. Blood Coagul Fibrinol 2000; 11 (Suppl. 01) S55-S68.
• 67 Porte RJ, Molenaar IQ, Begliomini B. et al. Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group. Lancet 2000; 355: 1289-1290.
• 68 Ramsay MA, Randall HB, Burton EC. Intravascular thrombosis and thromboembolism during liver transplantation: antifibrinolytic therapy implicated?. Liver Transpl 2004; 10: 310-314.
• 69 Roberts HR, Monroe 3rd DM, Escobar MA. Current concepts of hemostasis: implications for therapy. Anesthesiology 2004; 100: 722-730.
• 70 Rodewald I, Asmelash G, Böhm M. et al. Proteinchemische Untersuchung von 28 Chargen eines PPSB’s mit zwei effektiven Virusreduktionsschritten (Beriplex P/N) und die Zusammenfassung der Pharmakovigilanzdaten. Hämostaseologie. 2004 A46 (P28).
• 71 Sachs UJ, Kauschat D, Bein G. White blood cellreactive antibodies are undetectable in solvent/detergent plasma. Transfusion 2005; 45: 1628-1631.
• 72 Sankey EA, Crow J, Mallett SV. et al. Pulmonary platelet aggregates: possible cause of sudden peroperative death in adults undergoing liver transplantation. J Clin Pathol 1993; 46: 222-227.
• 73 Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990; 30: 583-590.
• 74 Scharrer I. Leberzirrhose und Gerinnungsstörungen. Hämostaseologie 2005; 25: 205-208.
• 75 Segal H, Cottam S, Potter D. et al. Coagulation and fibrinolysis in primary biliary cirrhosis compared with other liver disease and during orthotopic liver transplantation. Hepatology 1997; 25: 683-688.
• 76 Singbartl K, Innerhofer P, Radvan J. et al. Hemostasis and hemodilution: a quantitative mathematical guide for clinical practice. Anesth Analg 2003; 96: 929-935.
• 77 Spahn DR, Rossaint R. Coagulopathy and blood component transfusion in trauma. Br J Anaesth 2005; 95: 130-139.
• 78 Spiel AO, Mayr FB, Firbas C. et al. Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans. Thromb Haemost 2006; 4: 411-416.
• 79 Stanworth SJ, Brunskill SJ, Hyde CJ. et al. Is fresh frozen plasma effective? A systematic review of randomized controlled trials. Br J Haematol 2004; 126: 139-152.
• 80 Steib A, Gengenwin N, Freys G. et al. Predictive factors of hyperfibrinolytic activity during liver transplantation in cirrhotic patients. Br J Anaesth 1994; 73: 645-648.
• 81 Tacke F, Fiedler K, von Depka M. et al. Clinical and prognostic role of plasma coagulation factor XIII activity for bleeding disorders and 6-year survival in patients with chronic liver disease. Liver International 2006; 26: 173-181.
• 82 Takano K, Asazuma N, Satoh K. et al. Collagen-induced generation of platelet-derived microparticles in whole blood is dependent on ADP released from red blood cells and calcium ions. Platelets 2004; 15: 223-229.
• 83 Toy P, Popovsky MA, Abraham E. et al. National Heart, Lung and Blood Institute Working Group on TRALI. Transfusion-related acute lung injury: definition and review. Critical Care Med 2005; 33: 721-726.
• 84 Trobisch H, Wüst T. Antithrombin. Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten 3. Aufl. Köln: Deutscher Ärzteverlag; 2003: 159-170.
• 85 Turitto VT, Weiss HJ. Red blood cells: their dual role in thrombus formation. Science 1980; 207: 541-543.
• 86 Wolberg AS, Meng ZH, Monroe 3rd DM. et al. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma 2004; 56: 1221-1228.
• 87 Xia VW, Steadman RH. Antifibrinolytics in orthotopic liver transplantation: current status and controversies. Liver Transpl 2005; 11: 10-18.
• 88 Yomtovian R, Lazarus HM, Goodnough LT. et al. A prospective microbiologic surveillance program to detect and prevent the transfusion of bacterially contaminated platelets. Transfusion 1993; 33: 902-909.