Procoagulant therapeutics in liver disease: A critique and clinical rationale

Nature Reviews Gastroenterology and Hepatology

Volumn 11, Issue 11, 2014, Pages 675-682

  Shah, Neeral L ^a   Intagliata, Nicolas M ^a   Northup, Patrick G ^a   Argo, Curtis K ^a   Caldwell, Stephen H ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOCAPROIC ACID; ANTIFIBRINOLYTIC AGENT; ANTIVITAMIN K; APROTININ; BLOOD CLOTTING FACTOR 8; DESMOPRESSIN; FIBRINOGEN; FRESH FROZEN PLASMA; PLACEBO; PROCOAGULANT; PROTHROMBIN COMPLEX; RECOMBINANT BLOOD CLOTTING FACTOR 7A; TERLIPRESSIN; THROMBIN; TRANEXAMIC ACID; VITAMIN K GROUP; VON WILLEBRAND FACTOR; ARGIPRESSIN[1 DEAMINO]; BLOOD CLOTTING FACTOR 7A; COAGULATING AGENT; CRYOPRECIPITATE COAGULUM; RECOMBINANT FVIIA; RECOMBINANT PROTEIN;

ACUTE LIVER FAILURE; ANEMIA; BLEEDING; BLEEDING DISORDER; BLEEDING TIME; CHRONIC LIVER DISEASE; CONTINUOUS INFUSION; CRYOPRECIPITATE; END STAGE LIVER DISEASE; ERYTHROCYTE TRANSFUSION; FIBRINOGEN DEFECT; HEMATOCRIT; HEMOPHILIA; HEMOPHILIA A; HUMAN; INTERNATIONAL NORMALIZED RATIO; LIVER CIRRHOSIS; LIVER DISEASE; LIVER RESECTION; LIVER TRANSPLANTATION; LOADING DRUG DOSE; PARTIAL THROMBOPLASTIN TIME; PORTAL HYPERTENSION; PORTAL VEIN BLOOD PRESSURE; PROTHROMBIN TIME; REVIEW; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; THROMBOELASTOGRAPHY; THROMBOSIS; UREMIA; VARICEAL BLEEDING; VARICES BLEEDING; VITAMIN K DEFICIENCY; VON WILLEBRAND DISEASE; COMPLICATION; HEMORRHAGE; LIVER DISEASES; METABOLISM; PLASMA;

ANTIFIBRINOLYTIC AGENTS; COAGULANTS; DEAMINO ARGININE VASOPRESSIN; ERYTHROCYTE TRANSFUSION; FACTOR VIIA; FACTOR VIII; FIBRINOGEN; HEMORRHAGE; HUMANS; LIVER DISEASES; PLASMA; RECOMBINANT PROTEINS; VITAMIN K;

EID: 84908512545     PISSN: 17595045     EISSN: 17595053     Source Type: Journal    
DOI: 10.1038/nrgastro.2014.121     Document Type: Review

References (78)

1. Tripodi, A. & Mannucci, P. M. The coagulopathy of chronic liver disease. N. Engl. J. Med. 365, 147-156 (2011).
2. Northup, P. G. et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am. J. Gastroenterol. 101, 1524-1528 (2006).
3. Shah, N. L., Northup, P. G. & Caldwell, S. H. A clinical survey of bleeding, thrombosis and blood product use in decompensated cirrhosis patients. Ann. Hepatol. 11, 686-690 (2012).
4. Giannini, E. G. et al. Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease. Clin. Gastroenterol. Hepatol. 8, 899-902 (2010).
5. Furie, B. & Furie, B. C. Molecular basis of vitamin K-dependent gamma-carboxylation. Blood 75, 1753-1762 (1990).
6. Iber, F. L. et al. Vitamin K deficiency in chronic alcoholic males. Alcohol Clin. Exp. Res. 10, 679-681 (1986).
7. Saja, M. F. et al. The coagulopathy of liver disease: does vitamin K help? Blood Coagul. Fibrinolysis 24, 10-17 (2013).
8. Blanchard, R. A. et al. Acquired vitamin K-dependent carboxylation deficiency in liver disease. N. Engl. J. Med. 305, 242-248 (1981).
9. Choi, J. Y. et al. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J. Gastroenterol. 19, 339-346 (2013).
10. Pereira, S. P. et al. Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease. J. Hepatol. 42, 365-370 (2005).
11. O'Shaughnessy, D. F. et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br. J. Haematol. 126, 11-28 (2004).
12. Dirckx, J. H. Armand J. Quick: pioneer and prophet of coagulation research. Ann. Intern. Med. 92, 553-558 (1980).
13. Trotter, J. F. et al. Changes in international normalized ratio (INR) and model for endstage liver disease (MELD) based on selection of clinical laborator y. Am. J. Transplant. 7, 1624-1628 (2007).
14. Lisman, T. et al. Interlaboratory variability in assessment of the model of end-stage liver disease score. Liver Int. 28, 1344-1351 (2008).
15. Stravitz, R. T. Potential applications of thromboelastography in patients with acute and chronic liver disease. Gastroenterol. Hepatol. (NY) 8, 513-520 (2012).
16. Youssef, W. I. et al. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am. J. Gastroenterol. 98, 1391-1394 (2003).
17. Zimmon, D. S. & Kessler, R. E. The portal pressure-blood volume relationship in cirrhosis. Gut. 15, 99-101 (1974).
18. Moller, S., Bendtsen, F. & Henriksen, J. H. Effect of volume expansion on systemic hemodynamics and central and arterial blood volume in cirrhosis. Gastroenterology 109, 1917-1925 (1995).
19. Palascak, J. E. & Martinez, J. Dysfibrinogenemia associated with liver disease. J. Clin. Invest. 60, 89-95 (1977).
20. Boks, A. L. et al. Hemostasis and fibrinolysis n severe liver failure and their relation to hemorrhage. Hepatology 6, 79-86 (1986).
21. Northup, P. G. & Caldwell, S. H. Coagulation in liver disease: a guide for the clinician. Clin. Gastroenterol. Hepatol. 11, 1064-1074 (2013).
22. Giannini, E. G. & Savarino, V. Thrombocytopenia n liver disease. Curr. Opin. Hematol. 15, 473-480 (2008).
23. Lisman, T et al. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 44, 53-61 (2006).
24. Feys, H. B. et al. ADAMTS13 activity to antigen ratio in physiological and pathological conditions associated with an increased risk of thrombosis. Br. J. Haematol. 138, 534-540 (2007).
25. Ferro, D. et al. High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: relationship to endotoxemia. Hepatology 23, 1377-1383 (1996).
26. Argo, C. K. & Balogun, R. A. Blood products, volume control, and renal support in the coagulopathy of liver disease. Clin. Liver Dis. 13, 73-85 (2009).
27. Boccardo, P., Remuzzi, G. & Galbusera, M. Platelet dysfunction in renal failure. Semin. Thromb. Hemost. 30, 579-589 (2004).
28. Tripodi, A. et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 44, 440-445 (2006).
29. Hedner, U. et al. Successful use of recombinant factor VIIa in patient with severe haemophilia A during synovectomy. Lancet 332, 1193 (1988).
30. Bernstein, D. E. et al. Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study. Gastroenterology 113, 1930-1937 (1997).
31. Bosch, J. et al. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 127, 1123-1130 (2004).
32. Bosch, J. et al. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial. Hepatology 47, 1604-1614 (2008).
33. Romero-Castro, R. et al. Recombinant-activated factor VII as hemostatic therapy in eight cases of severe hemorrhage from esophageal varices. Clin. Gastroenterol. Hepatol. 2, 78-84 (2004).
34. Sartori, M. T. et al. Effect of recombinant activated factor VII in critical bleeding: clinical experience of a single center. Clin. Appl. Thromb. Hemost. 15, 628-635 (2009).
35. Meadows, H. B. et al. The use of activated recombinant factor VII in a patient with fulminant hepatic failure requiring placement of an intracranial pressure monitor. Ann. Pharmacother. 45, e60 (2011).
36. Shami, V. M. et al. Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl. 9, 138-143 (2003).
37. Stravitz, R. T. et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J. Hepatol. 56, 129-136 (2012).
38. Caldwell, S. H., Chang, C. & Macik, B. G. Recombinant activated factor VII (rFVIIa) as a hemostatic agent in liver disease: a break from convention in need of controlled trials. Hepatology 39, 592-598 (2004).
39. Violi, F. & Ferro, D. Clotting activation and hyperfibrinolysis in cirrhosis: implication for bleeding and thrombosis. Semin. Thromb. Hemost. 39, 426-433 (2013).
40. Caldwell, S. H. et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 44, 1039-1046 (2006).
41. Colucci, M. et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 38, 230-237 (2003).
42. Lisman, T. et al. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 121, 131-139 (2001).
43. Agarwal, S., Joyner, K. A. Jr, & Swaim, M. W. Ascites fluid as a possible origin for hyperfibrinolysis in advanced liver disease. Am. J. Gastroenterol. 95, 3218-3224 (2000).
44. Fergusson, D. A. et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N. Engl. J. Med. 358, 2319-2331 (2008).
45. Gunawan, B. & Runyon, B. The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis. Aliment. Pharmacol. Ther. 23, 115-120 (2006).
46. Howell, N. et al. Putting the record straight on aprotinin as safe and effective: results from a mixed treatment meta-analysis of trials of aprotinin. J. Thorac. Cardiovasc. Surg. 145, 234-240 (2013).
47. Mannucci, P. M. & Levi, M. Prevention and treatment of major blood loss. N. Engl. J. Med. 356, 2301-2311 (2007).
48. Franchini, M. & Lippi, G. Prothrombin complex concentrates: an update. Blood Transfus. 8, 149-154 (2010).
49. th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141 (Suppl. 2), e152S-e184S (2012).
50. FDA. Kcentra prescribing information [online], http://www. fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM350239.pdf.
51. Cederbaum, A. I., Blatt, P. M. & Roberts, H. R. Intravascular coagulation with use of human prothrombin complex concentrates. Ann. Intern. Med. 84, 683-687 (1976).
52. Lorenz, R. 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. 15, 15-20 (2003).
53. Mannucci, P. M., Franchi, F & Dioguardi, N. Correction of abnormal coagulation in chronic iver disease by combined use of fresh-frozen plasma and prothrombin complex concentrates. Lancet 308, 542-545 (1976).
54. Bick, R. L., Schmalhorst, W. R. & Shanbrom, E. Prothrombin complex concentrate: use in controlling the hemorrhagic diathesis of chronic iver disease. Am. J. Dig. Dis. 20, 741-749 (1975).
55. Green, G. et al. Use of factor-VII-rich prothrombin complex concentrate in liver disease. Lancet 305, 1311-1314 (1975).
56. Arshad, F et al. Prothrombin complex concentrate in the reduction of blood loss during orthotopic iver transplantation: PROTON-trial. BMC Surg. 13, 22 (2013).
57. Mannucci, P. M. et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N. Engl. J. Med. 308, 8-12 (1983).
58. Agnelli, G. et al. Desmopressin-induced improvement of abnormal coagulation in chronic iver disease. Lancet 321, 645 (1983).
59. Agnelli, G. et al. Effects of desmopressin on hemostasis in patients with liver cirrhosis. Haemostasis 25, 241-247 (1995).
60. de Franchis, R. 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. Hepatology 18, 1102-1107 (1993).
61. Stanca, C. M. et al. Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial. J. Oral Maxillofac. Surg. 68, 138-143 (2010).
62. Wong, A. Y. et al. Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy. Can. J. Anaesth. 50, 14-20 (2003).
63. Burroughs, A. K. et al. Desmopressin and bleeding time in patients with cirrhosis. Br. Med. J. (Clin. Res. Ed.) 291, 1377-1381 (1985).
64. Thachil, J. Anemia-the overlooked factor in bleeding related to liver disease. J. Hepatol. 54, 593-594 (2011).
65. Turitto, V T. & Baumgartner, H. R. Platelet interaction with subendothelium in a perfusion system: physical role of red blood cells. Microvasc. Res. 9, 335-344 (1975).
66. Turitto, V T. & Weiss, H. J. Red blood cells: their dual role in thrombus formation. Science 207, 541-543 (1980).
67. rd et al. The effect of red blood cells on thrombin generation. Br. J. Haematol. 133, 403-408 (2006).
68. Violi, F et al. Activation of platelet cyclooxygenase by red cells in vitro. N. Engl. J. Med. 313, 1091-1092 (1985).
69. Lisman, T. et al. No evidence for an intrinsic platelet defect in patients with liver cirrhosis -studies under flow conditions. J. Thromb. Haemost. 4, 2070-2072 (2006).
70. Escolar, G. et al. Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100): influence of hematocrit elevation. Haematologica 84, 614-619 (1999).
71. Lisman, T., Caldwell, S. H. & Porte, R. J. Anemia as a potential contributor to bleeding in patients with liver disease-neglected but not forgotten Reply. J. Hepatol. 54, 594-595 (2011).
72. Lisman, T & Porte, R. J. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 116, 878-885 (2010).
73. D'Amico, G. et al. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review. Gastroenterology 131, 1611-1624 (2006).
74. de Franchis, R. & Baveno, V. F. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J. Hepatol. 53, 762-768 (2010).
75. Kravetz, D. et al. Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting. Hepatology 9, 808-814 (1989).
76. Castaneda, B. et al. Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats. Hepatology 33, 821-825 (2001).
77. de Boer, M. T. et al. The impact of intraoperative transfusion of platelets and red blood cells on survival after liver transplantation. Anesth. Analg. 106, 32-44 (2008).
78. Massicotte, L. et al. Effects of phlebotomy and phenylephrine infusion on portal venous pressure and systemic hemodynamics during liver transplantation. Transplantation 89, 920-927 (2010).