Pharmacologic management of coagulopathy in cardiac surgery: An update

Journal of Cardiothoracic and Vascular Anesthesia

Volumn 26, Issue 4, 2012, Pages 669-679

  Rozental, Tatyana ^a   Shore Lesserson, Linda ^a  

^a MONTEFIORE MEDICAL CENTER   (United States)

Author keywords

antifibrinolytic; extracorporeal circulation; hemostasis; pharmacology

Indexed keywords

ADENOSINE DIPHOSPHATE; AMINOCAPROIC ACID; APROTININ; BLOOD CLOTTING FACTOR 12; BLOOD CLOTTING FACTOR 13; BLOOD CLOTTING FACTOR 5 LEIDEN; BRADYKININ; CU 2010; DESMOPRESSIN; ECALLANTIDE; FIBRINOLYTIC AGENT; GLYCOPROTEIN IB; HEPARIN; HIGH MOLECULAR WEIGHT KININOGEN; KALLIKREIN; NAFAMSTAT; PADGEM PROTEIN; PLASMIN; PROTHROMBIN COMPLEX; PROUROKINASE; RECOMBINANT BLOOD CLOTTING FACTOR 7A; SERINE PROTEINASE INHIBITOR; THROMBIN; THROMBOPLASTIN; TRANEXAMIC ACID; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR;

AORTA VALVE REPLACEMENT; ARTERY THROMBOSIS; BLOOD CLOTTING DISORDER; BLOOD TRANSFUSION; CARDIOPULMONARY BYPASS; CORONARY ARTERY; CORONARY ARTERY BYPASS GRAFT; DISSEMINATED INTRAVASCULAR CLOTTING; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; ERYTHROCYTE; EXTRACORPOREAL CIRCULATION; FIBRINOLYSIS; HEART SURGERY; HEMOPHILIA; HEMOSTASIS; HUMAN; KIDNEY DYSFUNCTION; MITRAL VALVE REPLACEMENT; PEROPERATIVE COMPLICATION; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIDE EFFECT; THROMBOCYTE ACTIVATION; THROMBOCYTE COUNT; THROMBOCYTE FUNCTION;

ANTIFIBRINOLYTIC AGENTS; BLOOD COAGULATION DISORDERS; BLOOD COAGULATION FACTORS; CARDIAC SURGICAL PROCEDURES; CARDIOPULMONARY BYPASS; DEAMINO ARGININE VASOPRESSIN; FACTOR VIIA; HUMANS; PROTEASE INHIBITORS;

EID: 84863467192     PISSN: 10530770     EISSN: 15328422     Source Type: Journal    
DOI: 10.1053/j.jvca.2012.03.030     Document Type: Review

References (113)

1. M. Herbertson Recombinant activated factor VII in cardiac surgery Blood Coagul Fibrinolysis 15 suppl 1 2004 S31 S32
2. C.G. Koch, L. Li, D.I. Sessler Duration of red-cell storage and complications after cardiac surgery N Engl J Med 358 2008 1229 1239 (Pubitemid 351439224)
3. V.A. Ferraris, J.R. Brown, G.J. Despotis 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines Ann Thorac Surg 91 2011 944 982
4. E. Bennett-Guerrero, H.K. Song, Y. Zhao Temporal changes in the use of blood products for coronary artery bypass graft surgery in North America: An analysis of the Society of Thoracic Surgeons Adult Cardiac Database J Cardiothorac Vasc Anesth 24 2010 814 816
5. D. Paparella, S.J. Brister, M.R. Buchanan Coagulation disorders of cardiopulmonary bypass: A review Intensive Care Med 30 2004 1873 1881 (Pubitemid 39468407)
6. M.D. Linden The hemostatic defect of cardiopulmonary bypass J Thromb Thrombolysis 16 2003 129 147 (Pubitemid 39137438)
7. W. Hueb, N.H. Lopes, A.C. Pereira Five-year follow-up of a randomized comparison between off-pump and on-pump stable multivessel coronary artery bypass grafting The MASS III trial Circulation 122 2010 S48 S52
8. C.H. Moller, M.J. Perko, J.T. Lund Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: The Best Bypass Surgery Trial Heart 97 2011 907 913
9. J.R. Pepper NICE guidance for off-pump CABG: Keep the pump primed Heart 97 2011 1728 1730
10. H. Bayram, D. Erer, E. Iriz Comparison of the effects of pulsatile cardiopulmonary bypass, non-pulsatile cardiopulmonary bypass and off-pump coronary artery bypass grafting on the inflammatory response and S-100beta protein Perfusion 27 2012 56 64
11. J. Butler, G.M. Rocker, S. Westaby Inflammatory response to cardiopulmonary bypass Ann Thorac Surg 55 1993 552 559 (Pubitemid 23060844)
12. R.C. Landis Redefining the systemic inflammatory response Semin Cardiothorac Vasc Anesth 13 2009 87 94
13. R. de Vroege, F. te Meerman, L. Eijsman Induction and detection of disturbed homeostasis in cardiopulmonary bypass Perfusion 19 2004 267 276 (Pubitemid 39365965)
14. C.S. Rinder, D. Gaal, L.A. Student Platelet-leukocyte activation and modulation of adhesion receptors in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass J Thorac Cardiovasc Surg 107 1994 280 288 (Pubitemid 24050529)
15. D.S. Holloway, L. Summaria, J. Sandesara Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients Thromb Haemost 59 1988 62 67 (Pubitemid 18053651)
16. C.S. Rinder, J.L. Bonan, H.M. Rinder Cardiopulmonary bypass induces leukocyte-platelet adhesion Blood 79 1992 1201 1205
17. C.S. Rinder, J. Bohnert, H.M. Rinder Platelet activation and aggregation during cardiopulmonary bypass Anesthesiology 75 1991 388 393
18. Y.T. Wachtogel, J. Musial, B. Jenkin Loss of platelet alpha 2-adrenergic receptors during simulated extracorporeal circulation: Prevention with prostaglandin E1 J Lab Clin Med 105 1985 601 607 (Pubitemid 15003242)
19. P. Gluszko, B. Rucinski, J. Musial Fibrinogen receptors in platelet adhesion to surfaces of extracorporeal circuit Am J Physiol 252 1987 H615 H621
20. E.W. Salzman, R.D. Rosenberg, M.H. Smith Effect of heparin and heparin fractions on platelet aggregation J Clin Invest 65 1980 64 73 (Pubitemid 10214332)
21. Y.T. Wachtfogel, U. Kucich, C.E. Hack Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion J Thorac Cardiovasc Surg 106 1993 1 10 (Pubitemid 23216041)
22. M.K. Dewanjee Molecular biology of nitric oxide synthases Reduction of complications of cardiopulmonary bypass from platelets and neutrophils by nitric oxide generation from l-arginine and nitric oxide donors ASAIO J 43 1997 151 159 (Pubitemid 27209176)
23. J.I. Weitz, M. Hudoba, D. Massel Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors J Clin Invest 86 1990 385 391 (Pubitemid 20271869)
24. P. Raivio, R. Lassila, J. Petäjä Thrombin in myocardial ischemia-reperfusion during cardiac surgery Ann Thorac Surg 88 2009 318 325
25. G.J. Despotis, M.S. Avidan, C.W. Hogue Jr Mechanisms and attenuation of hemostatic activation during extracorporeal circulation Ann Thorac Surg 72 2001 S1821 S1831
26. R.M. Sniecinski, W.L. Chandler Activation of the hemostatic system during cardiopulmonary bypass Anesth Analg 113 2011 1319 1333
27. S.J. Brister, F.A. Ofosu, M.R. Buchanan Thrombin generation during cardiac surgery: Is heparin the ideal anticoagulant? Thromb Haemost 70 1993 259 262 (Pubitemid 23222480)
28. K.A. Tanaka, J.H. Levy Regulation of thrombin activity - Pharmacologic and structural aspects Hematol Oncol Clin North Am 21 2007 33 50 (Pubitemid 46156984)
29. W.Z. Martini, D.S. Cortez, M.A. Dubick Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs J Trauma 65 2008 535 543
30. J.D. Olson, C.F. Arkin, J.T. Brandt College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: Laboratory monitoring of unfractionated heparin therapy Arch Pathol Lab Med 122 1998 782 798
31. M. Hoffman, D.M. Monroe Coagulation 2006: A modern view of hemostasis Hematol Oncol Clin North Am 21 2007 1 11 (Pubitemid 46135905)
32. F. Rubens An update on perioperative blood salvage in cardiac surgery TATM 7 2005 20 28
33. B. Ramlawi, J.L. Rudolph, S. Mieno Serologic markers of brain injury and cognitive function after cardiopulmonary bypass Ann Surg 244 2006 593 601
34. L. Gao, R. Taha, D. Gauvin Postoperative cognitive dysfunction after cardiac surgery Chest 128 2005 3664 3670 (Pubitemid 41698708)
35. M. Ide, D. Bolliger, T. Taketomi Lessons from the aprotinin saga: Current perspective on antifibrinolytic therapy in cardiac surgery J Anesth 24 2010 96 106
36. O. Shigeta, H. Kojima, T. Jikuya Aprotinin inhibits plasmin-induced platelet activation during cardiopulmonary bypass Circulation 96 1997 569 574 (Pubitemid 27329435)
37. A.M. Mengistu, K.D. Röhm, J. Boldt The influence of aprotinin and tranexamic acid on platelet function and postoperative blood loss in cardiac surgery Anesth Analg 107 2008 391 397
38. G. Soslau, J. Horrow, I. Brodsky Effect of tranexamic acid on platelet ADP during extracorporeal circulation Am J Hematol 38 1991 113 119
39. J.R. Day, P.P. Punjabi, A.M. Randi Clinical inhibition of the seven-transmembrane thrombin receptor (PAR1) by intravenous aprotinin during cardiothoracic surgery Circulation 110 2004 2597 2600 (Pubitemid 39453008)
40. J.H. Levy Antifibrinolytic therapy: New data and new concepts Lancet 376 2010 3 4
41. E. Bennett-Guerrero, S.H. Song, Y. Zhao Temporal changes in the use of blood products for coronary artery bypass graft surgery in North America: An analysis of the Society of Thoracic Surgeons Adult Cardiac Database J Cardiothorac Vasc Anesth 24 2010 814 816
42. H. Shakur, R. Roberts, R. Bautista CRASH-2 Trial Collaborators Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial Lancet 376 2010 23 32
43. J.H. Levy Anti-inflammatory strategies and hemostatic agents: Old drugs, new ideas Hematol Oncol Clin North Am 21 2007 89 101 (Pubitemid 46156983)
44. J.J. Jimenez, J.L. Iribarren, L. Lorente Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: A case control study followed by a randomized double-blind controlled trial Crit Care 11 2007 R117
45. M. Murase, A. Usui, Y. Tomita Nafamostat mesylate reduces blood loss during open heart surgery Circulation 88 1993 II432 II436
46. A. Skyring, A. Singer, P. Tornya Treatment of acute pancreatitis with Trasylol: Report of a controlled therapeutic trial Br Med J 2 1965 627 629
47. K.U. Kim, O.J. Kwon, D.M. Jue Pro-tumour necrosis factor cleavage enzyme in macrophage membrane/particulate Immunology 80 1993 134 139
48. D. Royston, J.S. Fleming, J.B. Desai Increased production of peroxidation products associated with cardiac operations Evidence for free radical generation J Thorac Cardiovasc Surg 91 1986 759 766 (Pubitemid 16114789)
49. D.T. Mangano, I.C. Tudor, C. Dietzel The risk associated with aprotinin in cardiac surgery N Engl J Med 354 2006 353 365 (Pubitemid 43145060)
50. D.A. Fergusson, P.C. Hébert, C.D. Mazer A comparison of aprotinin and lysine analogues in high-risk cardiac surgery N Engl J Med 358 2008 2319 2331 (Pubitemid 351749156)
51. Health Canada website http://www.hc-sc.gc.ca/ahc-asc/media/advisories- avis/-2011/2011-124-eng.php Accessed April 26, 2012
52. B.P. Bidstrup, S.R. Underwood, R.N. Sapsford Effect of aprotinin (Trasylol) on aorta-coronary bypass graft patency J Thorac Cardiovasc Surg 105 1993 147 153 (Pubitemid 23033772)
53. A. Kalangos, G. Tayyareci, R. Prêtre Influence of aprotinin on early graft thrombosis in patients undergoing myocardial revascularization Eur J Cardiothorac Surg 8 1994 651 656
54. E.L. Alderman, J.H. Levy, J.B. Rich Analyses of coronary graft patency after aprotinin use: Results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial J Thorac Cardiovasc Surg 116 1998 716 730 (Pubitemid 28499166)
55. R.C. Landis, G. Asimakopoulos, M. Poullis The antithrombotic and antiinflammatory mechanisms of action of aprotinin Ann Thorac Surg 72 2001 2169 2175 (Pubitemid 34002966)
56. W. Dietrich, G. Dilthey, M. Spannagl et al. Influence of high-dose of aprotinin on anticoagulation, heparin requirements, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open-heart surgery: A double-blind, placebo-controlled study Anesthesiology 83 1995 679 689
57. S. Okamoto, U. Okamoto Amino-Methyl-Cyclohexane-Carbolic-Acid: AMCHA A new potent inhibitor of fibrinolysis The Keio J of Medicine 11 1962 105 115
58. T. Syrovets, T. Simmet Novel aspects and new roles for the serine protease plasmin Cell Mol Life Sci 61 2004 873 885 (Pubitemid 38651004)
59. S.E. Fremes, B.I. Wong, E. Lee Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding Ann Thorac Surg 58 1994 1580 1588 (Pubitemid 24378960)
60. A. Laupacis, D. Fergusson Drugs to minimize perioperative blood loss in cardiac surgery: Meta-analyses using perioperative blood transfusion as the outcome The International Study of Peri-Operative Transfusion (ISPOT) investigators Anesth Analg 85 1997 1258 1267 (Pubitemid 28130521)
61. J.J. Munoz, N.J. Birkmeyer, J.D. Birkmeyer Is epsilon-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery?: A meta-analysis Circulation 99 1999 81 89 (Pubitemid 29035961)
62. D.A. Henry, P.A. Carless, A.J. Moxey et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion Cochrane Database Syst Rev 3 2011 CD001886
63. D.R. McIlroy, P.S. Myles, L.E. Phillips Antifibrinolytics in cardiac surgical patients receiving aspirin: A systematic review and meta-analysis Br J Anaesth 102 2009 168 178
64. J.M. Murkin, F. Falter, J. Granton High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients Anesth Analg 110 2010 350 353
65. R. Furtmüller, M.G. Schlag, M. Berger Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect J Pharmacol Exp Ther 301 2002 168 173 (Pubitemid 34256345)
66. S.N. Heyman, Z. Hanna, T. Nassar The fibrinolytic system attenuates vascular tone: Effects of tissue plasminogen activator (tPA) and aminocaproic acid on renal microcirculation Br J Pharmacol 141 2004 971 978 (Pubitemid 38510080)
67. Rhee A, Shore-Lesserson L, Lazar D: A randomized, double-blinded trial comparing the efficacy of tranexamic acid and epsilon-aminocaproic acid in reducing bleeding and transfusion in cardiac surgery. Presented at the 32nd SCA Annual Meeting, New Orleans, LA, 2010
68. K. Raghunathan, N.R. Connelly, G.J. Kanter ε-Aminocaproic acid and clinical value in cardiac anesthesia J Cardiothorac Vasc Anesth 25 2011 16 19
69. M.P. Eaton Antifibrinolytic therapy in surgery for congenital heart disease Anesth Analg 106 2008 1087 1100 (Pubitemid 351450530)
70. J. Karski, G. Djaiani, J. Carroll Tranexamic acid and early saphenous vein graft patency in conventional coronary artery bypass graft surgery: A prospective randomized controlled clinical trial J Thorac Cardiovasc Surg 130 2005 309 314 (Pubitemid 41074158)
71. J. Basha, R.C. Dewitt, D. Cable et al. Transfusions and their costs: managing patients needs and hospital economics The Internet Journal of Emergency and Intensive Care Medicine 9 2006
72. V. Casati, D. Guzzon, M. Oppizzi Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery Ann Thorac Surg 68 1999 2252 2256
73. L. Shore-Lesserson, D.L. Reich A case of severe diffuse venous thromboembolism associated with aprotinin and hypothermic circulatory arrest in a cardiac surgical patient with factor V Leiden Anesthesiology 105 2006 219 221 (Pubitemid 44305212)
74. M.A. Crowther, J.G. Kelton Congenital thrombophilic states associated with venous thrombosis: A qualitative overview and proposed classification system Ann Intern Med 138 2003 128 134 (Pubitemid 36222500)
75. S. Ogawa, J.E. Richardson, T. Sakai High mortality associated with intracardiac and intrapulmonary thromboses after cardiopulmonary bypass J Anesth 26 2012 9 19
76. T. Ohira, M. Cushman, M.Y. Tsai ABO blood group, other risk factors and incidence of venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE) J Thromb Hæmost JTH 5 2007 1455 1461 (Pubitemid 46965375)
77. V.M. Morelli, M.C. de Visser, N.H. van Tilburg ABO blood group genotypes, plasma von Willebrand factor levels and loading of von Willebrand factor with A and B antigens Thromb Haemost 97 2007 534 541 (Pubitemid 46592929)
78. O.D. Ratnoff Epsilon aminocaproic acid - A dangerous weapon N Engl J Med 280 1969 1124 1125
79. H.R. Gralnick, P. Greipp Thrombosis with epsilon aminocaproic acid therapy Am J Clin Pathol 56 1971 151 154
80. M. Franchini, P.M. Mannucci Interactions between genotype and phenotype in bleeding and thrombosis Haematologica 93 2008 649 652 (Pubitemid 351669303)
81. V. McMullan, R.P. Alston The effect of the suspension of the license for aprotinin on the care of patients undergoing cardiac surgery: A survey of cardiac anesthesiologists' and surgeons' opinions in the United Kingdom J Cardiothorac Vasc Anesth 24 2010 418 421
82. R.M. Sniecinski, E.P. Chen, S.S. Makadia Changing from aprotinin to tranexamic acid results in increased use of blood products and recombinant factor VIIa for aortic surgery requiring hypothermic arrest J Cardiothorac Vasc Anesth 24 2010 959 963
83. Z.Y. Strouch, M.L. Drum, M.A. Chaney Aprotinin use during cardiac surgery: Recent alterations and effects on blood product utilization J Clin Anesth 21 2009 502 507
84. X. Wang, Z. Zheng, H. Ao A comparison before and after aprotinin was suspended in cardiac surgery: Different results in the real world from a single cardiac center in China J Thorac Cardiovasc Surg 138 2009 897 903
85. X. Wang, Z. Zheng, H. Ao Effects of aprotinin on short-term and long-term outcomes after coronary artery bypass grafting surgery Ann Thorac Surg 89 2010 1489 1495
86. W. Dietrich, S. Nicklisch, A. Koster CU-2010 - A novel small molecule protease inhibitor with antifibrinolytic and anticoagulant properties Anesthesiology 110 2009 123 130
87. DX-88 (Kalbitor) Package Insert 2009 Dyax Corporation Cambridge, MA http://www.kalbitor.com/pdf/KalbitorFullPrescribingInformation.pdf
88. DX-88 Risk Evaluation and Management Strategy 2009 Dyax Corporation Cambridge, MA
89. K.A. O'Connell, J.J. Wood, R.P. Wise Thromboembolic adverse events after use of recombinant human coagulation factor VIIa JAMA 295 2006 293 298 (Pubitemid 43112957)
90. M. Tanos, J. Dunning Is recombinant activated factor VII useful for intractable bleeding after cardiac surgery? Interact Cardiovasc Thorac Surg 5 2006 493 498 (Pubitemid 44166466)
91. S. Gelsomino, R. Lorusso, S. Romagnoli Treatment of refractory bleeding after cardiac operations with low-dose recombinant activated factor VII (NovoSeven): A propensity score analysis Eur J Cardiothorac Surg 33 2008 64 71 (Pubitemid 350266356)
92. T. Lisman, P.G. De Groot Mechanism of action of recombinant factor VIIa J Thromb Haemost 1 2003 1138 1139
93. K. Karkouti, D.N. Wijeysundera, T.M. Yau The risk-benefit profile of aprotinin versus tranexamic acid in cardiac surgery Anesth Analg 110 2010 21 29
94. M. Levi, J.H. Levy, H.F. Andersen Safety of recombinant activated factor VII in randomized clinical trials N Engl J Med 363 2010 1791 1800
95. A. Patel, N. Cooper, M.A. Laffan Safety of recombinant activated factor VII in randomized clinical trials N Engl J Med 364 2011 574
96. O. Warren, K. Mandal, V. Hadjianastassiou Recombinant activated factor VII in cardiac surgery: A systematic review Ann Thorac Surg 83 2007 707 714 (Pubitemid 46138055)
97. L.L. Emlet, D. Crippen Early recombinant activated factor VII for intracerebral hemorrhage reduced hematoma growth and mortality, while improving functional outcomes Crit Care 10 2006 304
98. R. Gill, M. Herbertson, A. Vuylsteke Safety and efficacy of recombinant activated factor VII: A randomized placebo-controlled trial in the setting of bleeding after cardiac surgery Circulation 120 2009 21 27
99. K.A. Tanaka, T. Taketomi, F. Szlam Improved clot formation by combined administration of activated factor VII (NovoSeven) and fibrinogen (Haemocomplettan P) Anesth Analg 106 2008 732 738 (Pubitemid 351301386)
100. G.P. Gravlee, S. Arora, S.W. Lavender Predictive value of blood clotting tests in cardiac surgical patients Ann Thorac Surg 58 1994 216 221 (Pubitemid 24243933)
101. N. Rahe-Meyer, M. Pichlmaier, A. Haverich Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: A pilot study Br J Anaesth 102 2009 785 792
102. P. Wettstein, A. Haeberli, M. Stutz Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding Anesth Analg 99 2004 1564 1569 (Pubitemid 39407316)
103. C. Jámbor, V. Reul, T.W. Schnider In vitro inhibition of factor XIII retards clot formation, reduces clot firmness, and increases fibrinolytic effects in whole blood Anesth Analg 109 2009 1023 1028
104. G. Wozniak, T. Noll, H. Akintürk Factor XIII prevents development of myocardial edema in children undergoing surgery for congenital heart disease Ann N Y Acad Sci 936 2001 617 620 (Pubitemid 32613946)
105. S. Ohga, A. Nomura, H. Takada Successful self-infusion of activated prothrombin complex concentrate for prophylaxis in a child with a factor VIII inhibitor Am J Hematol 82 2007 145 149 (Pubitemid 46155277)
106. D. Bruce, T.J. Nokes Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: Experience in a large tertiary hospital Crit Care 12 2008 R105
107. L. Holland, T.E. Warkentin, M. Refaai Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose Transfusion 49 2009 1171 1177
108. D. Imberti, G. Barillari, C. Biasioli Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage Blood Transfus 9 2011 148 155
109. P. Innerhofer [Perioperative management of coagulation] Hamostaseologie 26 2006 S3 S14
110. Coagulation Management in Trauma Related Massive Bleeding http://www.oegari.at/arbeitsgruppe.asp Accessed April 27, 2012
111. M. Cattaneo, A.S. Harris, U. Strömberg The effect of desmopressin on reducing blood loss in cardiac surgery - A meta-analysis of double-blind, placebo-controlled trials Thromb Haemost 74 1995 1064 1070
112. M. Levi, M.E. Cromheecke, E. de Jonge Pharmacological strategies to decrease excessive blood loss in cardiac surgery: A meta-analysis of clinically relevant endpoints Lancet 354 1999 1940 1947
113. G.J. Despotis, V. Levine, R. Saleem Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: A randomised controlled trial Lancet 354 1999 106 110 (Pubitemid 29313144)