Current status of antifibrinolytics in cardiopulmonary bypass and elective deep hypothermic circulatory arrest

Anesthesiology Clinics of North America

Volumn 21, Issue 3, 2003, Pages 527-551

  Green, Jeffrey A ^a   Spiess, Bruce D ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; AMINOCAPROIC ACID; ANTIFIBRINOLYTIC AGENT; ANTIHISTAMINIC AGENT; ANTITHROMBIN III; APROTININ; ARGATROBAN; DERMATIN SULFATE; HEPARIN; HEPARIN DERIVATIVE; HIRULOG; LYSINE DERIVATIVE; MUSCLE RELAXANT AGENT; PENTASACCHARIDE; RECOMBINANT BLOOD CLOTTING FACTOR 7A; RECOMBINANT HIRUDIN; THROMBOXANE; TRANEXAMIC ACID; UNCLASSIFIED DRUG;

ANAPHYLAXIS; BLEEDING; BLOOD CLOTTING; CARDIOPULMONARY BYPASS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COST EFFECTIVENESS ANALYSIS; DEEP HYPOTHERMIC CIRCULATORY ARREST; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; FIBRINOLYSIS; HEART ARREST; HEMOSTASIS; HUMAN; HYPOTHERMIA; ISCHEMIA; META ANALYSIS; MULTICENTER STUDY; NEPHROTOXICITY; NEUROLOGIC DISEASE; OUTCOMES RESEARCH; PEROPERATIVE COMPLICATION; PROPHYLAXIS; RANDOMIZED CONTROLLED TRIAL; REVIEW; SIDE EFFECT; THROMBOSIS;

EID: 0141453790     PISSN: 08898537     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0889-8537(03)00042-7     Document Type: Review

References (163)

1. Magovern J, Sakert T, Benkhart D, et al. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg 1996;61:27-32.
2. Boyle E, Verrier E, Spiess B. Endothelial cell injury in cardiovascular surgery: The procoagulant response. Ann Thorac Surg 1996;62:1549-57.
3. Mongan P, Brown R, Thwaites B. Tranexamic acid and aprotinin reduce postoperative bleeding and transfusions during primary coronary revascularizations. Anesth Analg 1998;87:258-65.
4. Dodd R. The risk of transfusion-transmitted infection. N Engl J Med 1992;327:419-20.
5. Seyfried H, Walewska I. Immune hemolytic transfusion reactions. World J Surg 1987;11:25-9.
6. Greenbaum B. Transfusion-associated graft-versus-host disease: historical perspectives, incidence, and current use of irradiated blood products. J Clin Oncol 1991;9:1889-902.
7. Goodnough L, Brecher M, Kanter M, et al. Transfusion Medicine. N Engl J Med 1999;340: 438-47.
8. Klein H. Immunomodulatory aspects of transfusion: A once and future risk? Anesthesiology 1999;91:861-5.
9. Murphy P, Connery C, Hicks G, et al. Homologous blood transfusions as a risk factor for postoperative infection after coronary artery bypass operations. J Thorac Cardiovasc Surg 1992;104:1092-9.
10. Spiess B. Blood transfusion: The silent epidemic. Ann Thorac Surg 2001;72:S1832-7.
11. Nuttall G, Oliver W, Santrach P, et al. Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass. Anesthesiology 2001;94:773-81.
12. Despotis G, Filos K, Zoys T, et al. Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: A multivariate analysis in cardiac surgical patients. Anesth Analg 1996;82:13-21.
13. Dacey L, Munoz J, Baribeau Y, et al. Reexploration for hemorrhage following coronary artery bypass grafting: Incidence and risk factors. Arch Surg 1998;133:442-7.
14. Unsworth-White M, Herriot A, Valencia O, et al. Resternotomy for bleeding after cardiac operation: a marker for increased morbidity and mortality. Ann Thorac Surg 1995;59:664-7.
15. Moulton M, Creswell L, Mackey M, et al. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg 1996;111:1037-46.
16. Woodman R, Harker L. Bleeding complications associated with cardiopulmonary bypass. Blood 1990;76:1680-97.
17. Schumann F. Hemostatic restoration during cardiopulmonary bypass. In: Pifarre R, editor. New Anticoagulants for the Cardiovascular Patient. Philadelphia: Hanley & Belfus, Inc.; 1997. p. 453-69.
18. Alderman E, Levy J, Rich J, et al. Analyses of coronary graft patency after aprotinin use: Results from the international multicenter aprotinin graft patency experience (IMAGE) trial. J Thorac Cardiovasc Surg 1998;116:716-30.
19. Bennett-Guerrero E, Sorohan J, Gurevich M, et al. Cost-benefit and efficacy of aprotinin compared with epsilon-aminocaproic acid in patients having repeated cardiac operations: A randomized, blinded clinical trial. Anesthesiology 1997;87:1373-80.
20. Horrow J, Hlavacek J, Strong M, et al. Prophylactic tranexamic acid decreased bleeding after cardiac operations. J Thorac Cardiovasc Surg 1990;99:70-4.
21. Laupacis A, Fergusson D. Drugs to minimize perioperative blood loss in cardiac surgery: Meta-analyses using perioperative blood transfusion as the outcome. Anesth Analg 1997;85: 1258-67.
22. Levi M, Cromheecke M, de Jonge E, et al. Pharmacologic strategies to decrease excessive blood loss in cardiac surgery: A meta-analysis of clinically relevant endpoints. Lancet 1999; 354:1940-7.
23. Levy J, Pifarre R, Schaff H, et al. A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. Circulation 1995;92:2236-44.
24. Munoz J, Birkmeyer N, Birkmeyer J, et al. Is epsilon-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery? A meta-analysis. Circulation 1999;99:81-9.
25. Shore-Lesserson L, Reich D, Vela-Cantos F, et al. Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery. Anesth Analg 1996;83:18-26.
26. Sundt T, Kouchoukos N, Saffitz J, et al. Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest. Ann Thorac Surg 1993;55:1418-24.
27. Slaughter T, Faghih F, Greenberg C, et al. The effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery. Anesth Analg 1997;85:1221-6.
28. Ray M, Marsh N, Hawson G. Relationship of fibrinolysis and platelet function to bleeding after cardiopulmonary bypass. Blood Coagul Fibrinolysis 1994;5:679-85.
29. Despotis G, Santoro S, Spitznagel E, et al. Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg 1994;107:271-9.
30. Spiess B. The contribution of fibrinolysis to post bypass bleeding. J Cardiothorac Vasc Anesthesiology 1991;5:13-7.
31. Davie E, Fujikawa K, Kisiel W. The coagulation cascade: Initiation, maintenance, and regulation. Biochemistry 1991;30:10363-70.
32. Furie B, Furie BC. Molecular and cellular biology of blood coagulation. N Engl J Med 1992;326:800-6.
33. Dietrich W. Reducing thrombin formation during cardiopulmonary bypass: Is there a benefit of the additional anticoagulant action of aprotinin? J Cardiovasc Pharm 1996;27:S50-7.
34. Levy J. Pharmacologic preservation of the hemostatic system during cardiac surgery. Ann Thorac Surg 2001;72:S1814-20.
35. Boisclair M, Lane D, Philippou H, et al. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood 1993;82:3350-7.
36. de Haan J, Boonstra P, Monnink S, et al. Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis. Ann Thorac Surg 1995;59:901-7.
37. Heimark R, Kurachi K, Fujikawa K, et al. Surface activation of blood coagulation, fibrinolysis and kinin formation. Nature 1980;286:456-60.
38. Gravlee G, Haddon W, Rothberger H, et al. Heparin dosing and monitoring for cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:518-27.
39. Tanaka K, Takao M, Yada I, et al. Alterations in coagulation and fibrinolysis associated with cardiopulmonary bypass during open heart surgery. J Cardiothorac Anesth 1989;3:181.
40. Levin E, Stern D, Nawroth P, et al. Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. Thromb Haemost 1986;56: 115-9.
41. Murkin J. Cardiopulmonary bypass and the inflammatory response: A role for serine protease inhibitors? J Cardiothorac Vasc Anesth 1997;11:S19-23.
42. Vang S, Stammers A, Mejak B, et al. Co-administration of aprotinin and epsilon-aminocaproic acid during cardiopulmonary bypass in a swine model. J Extra-corporeal Tech 2000;32:196-206.
43. Teufelsbauer H, Proidl S, Havel M, et al. Early activation of hemostasis during cardiopulmonary bypass. Evidence for thrombin-mediated hyperfibrinolysis. Thromb Haemost 1992;68: 250-2.
44. Stibbe J, Kluft C, Brommer E, et al. Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest 1984;14:375-82.
45. Yoshihara H, Yamamoto T, Mihara H. Changes in coagulation and fibrinolysis occurring in dogs during hypothermia. Thromb Res 1985;37:503.
46. Umlas J. Fibrinolysis and disseminated intravascular coagulation in open heart surgery. Transfusion 1976;16:460.
47. Hanss M, Collen D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: Modulation by thrombin, endotoxin, histamine. J Lab Clin Med 1987;109:97-104.
48. Lu H, du Buit C, Soria J, et al. Postoperative hemostasis and fibrinolysis in patients undergoing cardiopulmonary bypass with or without aprotinin therapy. Thromb Haemost 1994;72: 438-43.
49. Benza RL, Paramo JA, Panizo C, et al. Gene polymorphisms for plasminogen activator inhibitor-1/tissue plasminogen activator and development of allograft coronary artery disease. Circulation 1998;98:2248-54.
50. Heinrich J, Funke H, Rust S, et al. Impact of polymorphisms in the alpha and beta fibrinogen gene and plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study. Arterial Thrombosis 1993;13:886-91.
51. Spannagl M, Dooijewaard G, Dietrich W, et al. Protection of single-chain urokinase-type plasminogen activator (scu- PA) in aprotinin treated cardiac surgical patients undergoing cardiopulmonary bypass. Thromb Haemost 1995;73:825-8.
52. Rinder C, Bohnert J, Rinder H, et al. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991;75:388.
53. Adelman B, Rizk A, Hanners E. Plasminogen interactions with platelets in plasma. Blood 1988;72:1530.
54. Despotis G, Avidan M, Hogue C. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg 2001;72:S1821-31.
55. Soslau G, Horrow J, Brodsky I. Effect of Tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol 1991;38:113-9.
56. van Oeveren W, Harder M, Roozendaal K, et al. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:788-97.
57. Lu H, Soria C, Li H, et al. Role of active center and lysine binding sites of plasmin in plasmin-induced platelet activation and disaggregation. Thromb Haemost 1991;65:67-72.
58. Lu H, Soria C, Soria J, et al. Reversible translocation of glycoprotein 1b in plasmin-treated platelets: Consequences for platelet function. Eur J Clin Invest 1993;23:785-93.
59. Vander Salm T, Ansell J, Okike O, et al. The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: A double-blind randomized study. J Thorac Cardiovasc Surg 1988;95:538-40.
60. Casati V, Guzzon D, Oppizi M, et al. Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery. Ann Thorac Surg 1999;68:2252-6.
61. Casati V, Guzzon D, Oppizi M, et al. Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: Effects on perioperative bleeding and allogeneic transfusions. J Thorac Cardiovasc Surg 2000;120:520-7.
62. Daily P, Lamphere J, Dembitsky W. Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. J Thorac Cardiovasc Surg 1994;108:99-108.
63. DelRossi A, Cernaianu A, Bostros S, et al. Prophylactic treatment of post perfusion bleeding using EACA. Chest 1989;96:27-30.
64. Jordan D, Delphin E, Rose E. Prophylactic epsilon-aminocaproic acid (EACA) administration minimizes blood replacement therapy during cardiac surgery. Anesth Analg 1995;80:827-9.
65. Karski J, Teasdale S, Norman P, et al. Prevention of post bypass bleeding with tranexamic acid and epsilon-aminocaproic acid. J Cardiothorac Vasc Anesth 1993;7:431-5.
66. Montesano R, Gustafson P, Palanzo D, et al. The effect of low-dose epsilon-aminocaproic acid on patients following coronary artery bypass surgery. Perfusion 1996;11:53-6.
67. Rousou J, Engelman R, Flack J, et al. Tranexamic acid significantly reduces blood loss associated with coronary revascularization. Ann Thorac Surg 1995;59:671-5.
68. Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs 1985;29:236.
69. Andersson L, Eriksson O, Hedlund P, et al. Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases. Urol Res 1978;6:83-8.
70. Butterworth J, James R, Kennedy D, et al. Pharmacokinetics of epsilon-aminocaproic acid in adult patients undergoing coronary artery surgery. Anesthesiology 1996;85:A151.
71. Horrow J, DiGregorio G, Ruch E, et al. The dose-plasma concentration relationship of tranexamic acid during surgery. Am J Ther 1994;1:206-9.
72. McClure P, Izsak J. The use of epsilon-aminocaproic acid to reduce bleeding during cardiac bypass in children with congenital heart disease. Anesthesiology 1974;40:604.
73. Midell A, Hallman G, Bloodwell R, et al. Epsilon-aminocaproic acid for bleeding after cardiopulmonary bypass. Ann Thorac Surg 1971;11:577.
74. Horrow J, van Riper D, Strong M, et al. The hemostatic effects of tranexamic acid and desmopressin during cardiac surgery. Circulation 1991;84:2063.
75. Gans H, Krivit W. Problems in hemostasis during open heart surgery. III: Epsilon-aminocaproic acid as an inhibitor of plasminogen activator activity. Ann Surg 1962;15:268-76.
76. Gans H, Subramanian V, John S, et al. Theoretical and practical (clinical) considerations concerning proteolytic enzymes and their inhibitors with particular reference to changes in the plasminogen-plasmin system observed during assisted circulation in man. Ann N Y Acad Sci 1968;146:721-36.
77. Okamoto S, Oshiba S, Mihara H, et al. Synthetic inhibitors of fibrinolysis: In vitro and in vivo mode of action. Ann N Y Acad Sci 1968;146:414-29.
78. Fremes S, Wong B, Lee E, et al. Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding. Ann Thorac Surg 1994;58:1580-8.
79. Hardy J, Belisle S. Natural and synthetic antifibrinolytics in adult cardiac surgery: Efficacy, effectiveness and efficiency. Can J Anaesth 1994;41:1104-12.
80. Bergin J. Complications of therapy with epsilon-aminocaproic acid. Med Clin North Am 1966;50:1669-78.
81. Dentz M, Slaughter T, Mark J. Early thrombus formation on heparin-bonded pulmonary artery catheters in patients receiving epsilon-aminocaproic acid. Anesthesiology 1995;82:583-6.
82. Ratnoff O. Epsilon-aminocaproic acid: A dangerous weapon. N Engl J Med 1969;280:1124-5.
83. Menichetti A, Tritapepe L, Ruvolo G, et al. Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: Aprotinin vs. tranexamic acid vs. epsilon-aminocaproic acid. J Cardiovasc Surg 1996;37:401-7.
84. Penta de Peppo A, Pierri M, Scafuri A, et al. Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery: Prospective trial of 3 antifibrinolytic drugs. Tex Heart Inst J 1995;22:231-6.
85. Horrow J, van Riper D, Strong M, et al. The dose-response relationship of tranexamic acid. Anesthesiology 1995;82:383-92.
86. Speekenbrink R, Vonk A, Wildevuur C, et al. Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary artery bypass grafting. Ann Thorac Surg 1995;59:438-42.
87. Blauhut B, Harringer W, Bettelheim P, et al. Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994;108:1083-91.
88. Corbeau J, Monrigal J, Jacob J, et al. Comparative effects of aprotinin and tranexamic acid on blood loss in cardiac surgery. Ann Fr Anesth Reanim 1995;14:154-61.
89. Katsaros D, Petricevic M, Snow N, et al. Tranexamic acid reduces post bypass blood use: A double-blind, prospective, randomized study of 210 patients. Ann Thorac Surg 1996;61:1131-5.
90. Brown R, Thwaites B, Mongan P. Tranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: A double-blind, randomized, placebo-controlled trial. Anesth Analg 1997;85:963-70.
91. Nuttall G, Oliver W, Ereth M, et al. Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding. Anesthesiology 2000;92:674-82.
92. Casati V, Bellotti F, Gerli C, et al. Tranexamic acid administration after cardiac surgery: A prospective, randomized, double-blind, placebo-controlled study. Anesthesiology 2001; 94:8-14.
93. Wong B, McLean R, Fremes S, et al. Aprotinin and tranexamic acid for high transfusion risk cardiac surgery. Ann Thorac Surg 2000;69:808-16.
94. Lindoff C, Rybo G, Astedt B. Treatment with tranexamic acid during pregnancy, and the risk of thromboembolic complications. Thromb Haemost 1993;70:238-40.
95. Ovrum E, Holen E, Abdelnoor M, et al. Tranexamic acid (cyclocapron) is not necessary to reduce blood loss after coronary bypass operations. J Thorac Cardiovasc Surg 1993;105:78-83.
96. Royston D. The serine antiprotease aprotinin (Trasylol): A novel approach to reducing postoperative bleeding. Blood Coag Fibrin 1990;1:55.
97. Bidstrup B, Royston D, Sapsford R, et al. Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin (Trasylol). J Thorac Cardiovasc Surg 1989;97: 364-72.
98. Blauhut B, Gross C, Necek S, et al. Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1991;101:958-67.
99. Dietrich W, Spannagl M, Jochum M, et al. Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Anesthesiology 1990;73:1119-26.
100. Lass M, Welz A, Kochs M, et al. Aprotinin in elective primary bypass surgery. Graft patency and clinical efficacy. Eur J Cardiothorac Surg 1995;9:206-10.
101. Lemmer J, Dilling E, Morton J, et al. Aprotinin for primary coronary artery bypass grafting: A multicenter trial of three dose regimens. Ann Thorac Surg 1996;62:1659-67.
102. Poullis M, Manning R, Laffan M, et al. The antithrombotic effect of aprotinin: Actions mediated via the protease-activated receptor 1. J Thorac Cardiovasc Surg 2000;120:370-8.
103. Chabbat J, Porte P, Tellier M, et al. Aprotinin is a competitive inhibitor of the factor VIIa-tissue factor complex. Thromb Res 1993;71:205-15.
104. Horrow J. Transfusion medicine and coagulation disorders. In: Kaplan JA, editor. Cardiac Anesthesia. Philadelphia: WB Saunders; 1987. p. 1111-54.
105. Marx G, Pokar K, Reuter H, et al. The effects of aprotinin on hemostatic function during cardiac surgery. J Cardiothorac Vasc Anesth 1991;5:467-74.
106. Edmunds L, Niewiarowski S, Colman R. Aprotinin (letter). J Thorac Cardiovasc Surg 1991; 101:1103.
107. Wenger R, Lukasiewicz H, Mikuta B, et al. Loss of platelet fibrinogen receptors during clinical cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989;97:235-9.
108. Huang H, Ding W, Su Z, et al. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc Surg 1993;106:11-8.
109. Tabuchi N, De Haan J, Boonstra P, et al. Aprotinin effect on platelet function and clotting during cardiopulmonary bypass. Eur J Cardiothorac Surg 1994;8:87-90.
110. John L, Rees G, Kovacs I. Reduction of heparin binding to and inhibition of platelets by aprotinin. Ann Thorac Surg 1993;55:1175-9.
111. Landis R, Asimakopoulos G, Poullis M, et al. The antithrombotic and anti-inflammatory mechanisms of action of aprotinin. Ann Thorac Surg 2001;72:2169-75.
112. Landis R, Haskard D, Taylor K. New anti-inflammatory and platelet-preserving effects of aprotinin. Ann Thorac Surg 2001;72:S1808-13.
113. Poullis M, Landis R, Taylor K. Aprotinin: Is it prothrombotic? Perfusion 2001;16:401-9.
114. Clagett G, Anderson F, Levine M, et al. Prevention of venous thromboembolism. Chest 1992;102:3915-4075.
115. Murkin J, Shannon N, Bourne R, et al. Aprotinin decreases blood loss in patients undergoing revision or bilateral total hip arthroplasty. Anesth Analg 1995;80:343-8.
116. Harmon D. Cost/benefit analysis of pharmacologic hemostasis. Ann Thorac Surg 1996;61: S21-5.
117. Royston D, Bidstrup B, Taylor K, et al. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 1987;ii:1289-91.
118. van Oeveren W, Jansen N, Bidstrup B, et al. Effects of aprotinin on hemostatic mechanism during cardiopulmonary bypass. Ann Thorac Surg 1987;44:640-5.
119. Royston D. High-dose aprotinin therapy: A review of the first five years' experience. J Cardiothorac Vasc Anesth 1992;6:76-100.
120. Tice D, Reed G, Clauss R, et al. Hemorrhage due to fibrinolysis occurring with open-heart operations. J Thorac Cardiovasc Surg 1963;46:673-9.
121. Bidstrup B, Underwood S, Sapsford R, et al. Effect of aprotinin (Trasylol) on aorto-coronary bypass graft patency. J Thorac Cardiovasc Surg 1993;105:147-53.
122. Bidstrup B. Pretreatment with aprotinin and aspirin. In: Pifarre R, editor. Blood Conservation with Aprotinin. Philadelphia: Hanley & Belfus; 1995. p. 1-44.
123. Murkin J, Lux J, Shannon N, et al. Aprotinin significantly decreases bleeding and transfusion requirements in patients receiving aspirin and undergoing cardiac operations. J Thorac Cardiovasc Surg 1994;107:554-61.
124. Harder M, Eijsman L, Roozendaal K, et al. Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass. Ann Thorac Surg 1991; 51:936-41.
125. Fraedrich G, Engler H, Kanz L, et al. High dose aprotinin regimen in cardiac surgery - A prospective randomised double-blind trial. Circulation 1989;80SII:158.
126. Dementieva I, Dzemeshkevich S, Charnaya M, et al. The use of high doses of aprotinin to decrease blood loss in aortocoronary bypass surgery. J Cardiovasc Surg 1994;35SI:185-6.
127. Swart M, Gordon P, Hayse-Gregson P, et al. High-dose aprotinin in cardiac surgery - A prospective randomized study. Anaesth Intens Care 1994;22:529-33.
128. Casas J, Zuazu-Jausoro I, Mateo J, et al. Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1995;110:1107-17.
129. Lemmer J, Stanford W, Bonney S, et al. Aprotinin for coronary bypass operations: Efficacy, safety, and influence on early saphenous vein graft patency. J Thorac Cardiovasc Surg 1994;107:543-53.
130. Cosgrove D, Heric B, Lytle B, et al. Aprotinin therapy for reoperative myocardial revascularization: A placebo-controlled study. Ann Thorac Surg 1992;54:1031-8.
131. Minami K, Notohamiprodjo G, Buschler H, et al. Alpha-2-plasmin inhibitor-plasmin complex and postoperative blood loss: Double-blind study with aprotinin in reoperation for myocardial revascularization. J Thorac Cardiovasc Surg 1993;106:934-6.
132. Davis R, Whittington R. Aprotinin. A review of its pharmacology and therapeutic efficacy in reducing blood loss associated with cardiac surgery. Drugs 1995;49:954-83.
133. Fraedrich G, Neukamm K, Schneider T, et al. Safety and risk/benefit assessment of aprotinin in primary CABG. In: Friedel N, Hetzer R, Royston D, editors. Blood use in cardiac surgery. Darmstadt: Steinkopff Verlag; 1991. p. 221-31.
134. Lemmer J, Stanford W, Bonney S, et al. Aprotinin for coronary artery bypass grafting: Effect on postoperative renal function. Ann Thorac Surg 1995;59:132-6.
135. Lemmer J, Metzdorf M, Krause A, et al. Aprotinin use in patients with dialysis-dependent renal failure undergoing cardiac operations. J Thorac Cardiovasc Surg 1996;112:192-4.
136. Bohrer H, Bach A, Fleischer F, et al. Adverse haemodynamic effects of high-dose aprotinin in a paediatric cardiac surgical patient. Anaesthesia 1990;45:853.
137. Goldstein D, Oz M, Smith C, et al. Safety of repeat aprotinin administration for LVAD recipients undergoing cardiac transplantation. Ann Thorac Surg 1996;61:692-5.
138. Dietrich W, Spath P, Ebell A, et al. Incidence of anaphylactic reactions to aprotinin - analysis of 248 reexposures to aprotinin. Anesthesiology 1995;83S:A104.
139. Lamparter-Schummert B, Mugaragu I, Hetzer R, et al. Aprotinin re-exposure in patients undergoing repeat cardiac surgery: Effect of prophylaxis with H1- and H2-receptor antagonists. Br J Anaesth 1995;74:S3.
140. Bohrer H, Fleischer F, Lang J, et al. Early formation of thrombi on pulmonary artery catheters in cardiac surgical patients receiving high-dose aprotinin. J Cardiothorac Vasc Anesthesiology 1990;4:222-5.
141. Umbrain V, Christiaens F, Camu F. Intraoperative coronary thrombosis: Can aprotinin and protamine be incriminated? J Cardiothorac Vasc Anesth 1994;8:198-201.
142. Van der Meer J, Hillege H, Ascoop C, et al. Aprotinin in aorto-coronary bypass surgery: Increased risk of vein graft occlusion and myocardial infarction? Supportive evidence from a retrospective study. Thromb Haemost 1996;75:1-3.
143. Dietrich W, Dilthey G, Spannagl M, et al. Influence of high-dose aprotinin on anticoagulation, heparin requirement, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open heart surgery. A double-blind, placebo-controlled study. Anesthesiology 1995;83:679.
144. Dietrich W, Jochum M. Effect of celite and kaolin on activated clotting time in the presence of aprotinin: Activated clotting time is reduced by binding of aprotinin to kaolin. J Thorac Cardiovasc Surg 1995;109:177-8.
145. Huyzen R, Harder M, Huet R, et al. Alternative perioperative anticoagulation monitoring during cardiopulmonary bypass in aprotinin-treated patients. J Cardiothorac Vasc Anesth 1994;8:153-6.
146. Wang J, Lin C, Hung W, et al. Monitoring of heparin induced anticoagulation with kaolin-activated clotting time in cardiac surgical patients treated with aprotinin. Anesthesiology 1992;77:1080-4.
147. Niemcryk S, Pettersson G, Rasmussen C, et al. Follow-up analyses of the international multicenter aprotinin graft patency experience (IMAGE). J Out Res 2001;5:1-10.
148. Kalangos A, Tayyareci G, Pretre R, et al. Influence of aprotinin on early graft thrombosis in patients undergoing myocardial revascularization. Eur J Cardiothorac Surg 1994;8:651-6.
149. Royston D. Aprotinin vs. lysine analogues: The debate continues. Ann Thorac Surg 1998;65: S9-19.
150. Havel M, Grabenwoger F, Schneider J, et al. Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood. J Thorac Cardiovasc Surg 1994;107:807-10.
151. Mora Mangano C, Neville M, Ping H, et al. Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory arrest. Circulation 2001;104:1276-81.
152. Espana F, Esrelles A, Griffin J, et al. Aprotinin is a competitive inhibitor of activated protein C. Thromb Res 1989;56:751-6.
153. Westaby S. Coagulation disturbances in profound hypothermia: The influence of antifibrinolytic therapy. Semin Thorac Cardiovasc Surg 1997;9:246-56.
154. Westaby S. Safety and efficacy of aprotinin in profoundly hypothermic circulatory arrest. J Card Surg 1997;12S:207-13.
155. Westaby S, Forni A, Dunning J, et al. Aprotinin and bleeding in profoundly hypothermic perfusion. Eur J Cardiothorac Surg 1994;8:82-6.
156. Ehrlich M, Grabenwoger M, Cartes-Zumelzu F, et al. Operations on the thoracic aorta and hypothermic circulatory arrest: Is aprotinin safe? J Thorac Cardiovasc Surg 1998;115:220-5.
157. Parolari A, Antona C, Alamanni F, et al. Aprotinin and deep hypothermic circulatory arrest: There are no benefits even when appropriate amounts of heparin are given. Eur J Cardiothorac Surg 1997;11:149-56.
158. Goldstein D, DeRosa C, Mongero L, et al. Safety and efficacy of aprotinin under conditions of deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg 1995;110:1615-22.
159. Okita Y, Takamoto S, Ando M, et al. Is use of aprotinin safe with deep hypothermic circulatory arrest in aortic surgery? Investigations on blood coagulation. Circulation 1996;94SI1:177-81.
160. Seigne P, Shorten G, Johnson R, et al. The effects of aprotinin on blood product transfusion associated with thoracic aortic surgery requiring deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth 2000;14:676-81.
161. Hashimoto K, Yamagishi M, Sasaki T, et al. Heparin and antithrombin III levels during cardiopulmonary bypass: Correlation with sub clinical plasma coagulation. Ann Thorac Surg 1995;58:799-805.
162. Levy J, Despotis G, Olson P, et al. Transgenically produced recombinant human ATIII enhances the antithrombotic effects of heparin in patients undergoing cardiac surgery. Blood 1997; 90:298.
163. Al Douri M, Shafi T, Al Khudairi D, et al. Effect of the administration of recombinant activated factor VII (rFVIIa; NovoSeven) in the management of severe uncontrolled bleeding in patients undergoing heart valve replacement surgery. Blood Coagul Fibrinol 2000;11:S121-7.