Antifibrinolytic therapy in surgery for congenital heart disease

Anesthesia and Analgesia

Volumn 106, Issue 4, 2008, Pages 1087-1100

  Eaton, Michael P ^a,b  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b Box 604 ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOCAPROIC ACID; APROTININ; PLACEBO; TRANEXAMIC ACID;

ANAPHYLAXIS; BLEEDING; CLINICAL TRIAL; CONGENITAL HEART DISEASE; CONTINUOUS INFUSION; CONTROLLED CLINICAL TRIAL; DRUG EFFECT; DRUG EFFICACY; DRUG FATALITY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; HEART INFARCTION; HEART SURGERY; HUMAN; HYPOTENSION; KIDNEY FAILURE; LOADING DRUG DOSE; LOW DRUG DOSE; MYOPATHY; POSTOPERATIVE PERIOD; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REVIEW; SKIN TEST; STROKE; THROMBOSIS;

EID: 41349087807     PISSN: 00032999     EISSN: None     Source Type: Journal    
DOI: 10.1213/ane.0b013e3181679555     Document Type: Article

References (121)

1. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003;75:S715-20
2. Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review. Intensive Care Med 2004;30:1873-81
3. Gans H, Krivit W. Problems in hemostasis during open-heart surgery. III. Epsilon amino caproic acid as an inhibitor of plasminogen activator activity. Ann Surg 1962;155:268-76
4. Ambrus J, Schimert G, Lajos T, Ambrus C, Mink I, Lassman H, Moore R, Melzer J. Effect of antifibrinolytic agents and estrogens on blood loss and blood coagulation factors during open heart surgery. J Med 1971;2:65-81
5. Kern FH, Morana NJ, Sears JJ, Hickey PR. Coagulation defects in neonates during cardiopulmonary bypass. Ann Thorac Surg 1992;54:541-6
6. Mossinger H, Dietrich W, Braun SL, Jochum M, Meisner H, Richter JA. High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery. Ann Thorac Surg 2003;75:430-7
7. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation system in the full-term infant. Blood 1987;70:165-72
8. Kuhle S, Male C, Mitchell L. Developmental hemostasis: pro- and anticoagulant systems during childhood. Semin Thromb Hemost 2003;29:329-38
9. Albisetti M. The fibrinolytic system in children. Semin Thromb Hemost 2003;29:339-48
10. Ries M, Easton RL, Longstaff C, Zenker M, Morris HR, Dell A, Gaffney PJ. Differences between neonates and adults in carbohydrate sequences and reaction kinetics of plasmin and alpha(2)-antiplasmin. Thromb Res 2002;105:247-56
11. Zenker M, Ries M. Differences between neonates and adults in plasmin inhibitory and antifibrinolytic action of aprotinin. Thromb Res 2002;107:17-21
12. Bahnson H, Ziegler R. A consideration of the causes of death following operation for congenital heart disease of the cyanotic type. Surg Gynecol Obstet 1950;90:60-76
13. Goldschmidt B, Sarkadi B, Gardos G, Matlary A. Platelet production and survival in cyanotic congenital heart disease. Scand J Haematol 1974;13:110-5
14. Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR. Loss of the largest von willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986;67:758-61
15. Dennis LH, Stewart JL, Conrad ME. Heparin treatment of haemorrhagic diathesis in cyanotic congenital heart-disease. Lancet 1967;1:1088-9
16. Stammers AH, Rauch ED, Willett LD, Newberry JW, Duncan KF. Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study. Perfusion 2000;15:161-8
17. Brodsky I, Gill DN, Lusch CJ. Fibrinolysis in congenital heart disease. Preoperative treatment with epsilon-aminocaproic acid. Am J Clin Pathol 1969;51:51-7
18. Petaja J, Lundstrom U, Leijala M, Peltola K, Siimes MA. Bleeding and use of blood products after heart operations in infants. J Thorac Cardiovasc Surg 1995;109:524-9
19. Boldt J, Knothe C, Zickmann B, Wege N, Dapper F, Hempelmann G. Aprotinin in pediatric cardiac operations: platelet function, blood loss, and use of homologous blood. Ann Thorac Surg 1993;55:1460-6
20. Reid RW, Zimmerman AA, Laussen PC, Mayer JE, Gorlin JB, Burrows FA. The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 1997;84:990-6
21. Chauhan S, Bisoi A, Kumar N, Mittal D, Kale S, Kiran U, Venugopal P. Dose comparison of tranexamic acid in pediatric cardiac surgery. Asian Cardiovasc Thorac Ann 2004;12:121-4
22. Chauhan S, Das SN, Bisoi A, Kale S, Kiran U. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 2004;18:141-3
23. Chauhan S, Kumar BA, Rao BH, Rao MS, Dubey B, Saxena N, Venugopal P. Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease. Ann Thorac Surg 2000;70:1308-12
24. Spiess BD. Transfusion of blood products affects outcome in cardiac surgery. Semin Cardiothorac Vasc Anesth 2004;8:267-81
25. Munoz JJ, Birkmeyer NJ, Birkmeyer JD, O'Connor GT, Dacey LJ. Is epsilon-aminocaproic acid as effective as aprotinin in reducing bleeding with cardiac surgery?: a meta-analysis. Circulation 1999;99:81-9
26. Sedrakyan A, Treasure T, Elefteriades JA. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. J Thorac Cardiovasc Surg 2004;128:442-8
27. Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR, Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the society of thoracic surgeons and the society of cardiovascular anesthesiologists clinical practice guideline. Ann Thorac Surg 2007;83:S27-86
28. Karkouti K, Beattie WS, Dattilo KM, McCluskey SA, Ghannam M, Hamdy A, Wijeysundera DN, Fedorko L, Yau TM. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006;46:327-38
29. Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354:353-65
30. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12
31. van der Staak FH, de Haan AF, Geven WB, Festen C. Surgical repair of congenital diaphragmatic hernia during extracorporeal membrane oxygenation: hemorrhagic complications and the effect of tranexamic acid. J Pediatr Surg 1997;32:594-9
32. Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet adp during extracorporeal circulation. Am J Hematology 1991;38:113-9
33. Casati V, Della Valle P, Benussi S, Franco A, Gerli C, Baili P, Alfieri O, D'Angelo A. Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: comparison between on-pump and off-pump techniques. J Thorac Cardiovasc Surg 2004;128:83-91
34. Greilich PE, Brouse CF, Whitten CW, Chi L, Dimaio JM, Jessen ME. Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon-aminocaproic acid and aprotinin. J Thorac Cardiovasc Surg 2003;126:1498-503
35. Asehnoune K, Dehoux M, Lecon-Malas V, Toueg ML, Gonieaux MH, Omnes L, Desmonts JM, Durand G, Philip I. Differential effects of aprotinin and tranexamic acid on endotoxin desensitization of blood cells induced by circulation through an isolated extracorporeal circuit. J Cardiothorac Vasc Anesth 2002;16:447-51
36. Hardy J-F, Belisle S. Natural and synthetic antifibrinolytics in adult surgery: efficacy, effectiveness and efficiency. Can J Anaesth 1994;44:1104-12
37. Levi M, Cromheecke ME, de Jonge E, Prins MH, de Mol BJ, Briet E, Buller HR. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999;354:1940-7
38. Amicar package insert: Xanodyne Pharmaceuticals, Inc., Newport, KY. April 2005
39. Nilsson IM, Sjoerdsma A, Waldenstrom J. Antifibrinolytic activity and metabolism of 6-aminocaproic acid in man. Lancet 1960;1:1322-6
40. Fiechtner BK, Nuttall GA, Johnson ME, Dong Y, Sujirattanawimol N, Oliver WC Jr, Sarpal RS, Oyen LJ, Ereth MH. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg 2001;92:1131-6
41. McNicol G, Fletcher A, Alkjaersig N, Sherry S. The absorption, distribution, and excretion of epsilon-aminocaproic acid following oral or intravenous administration to man. J Lab Clin Med 1962;59:15-24
42. Cyklokapron package insert. Pharmacia and Ujohn Division of Pfizer, New York, NY. November 2005
43. Pilbrant A, Schannong M, Vessman J. Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol 1981;20:65-72
44. Trasylol package insert: Bayer Pharmaceuticals Corporation, West Haven, CT. December 2006
45. Van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CR. Aprotinin protects platelets against the initial effect of cardiopumonary bypass. J Thorac Cardiovasc Surg 1990;99:788-97
46. Dietrich W. Reducing thrombin formation during cardiopulmonary bypass: is there a benefit of the additional anticoagulant action of aprotinin? J Cardiovasc Pharmacol 1996;27:S50-7
47. McEvoy MD, Reeves ST, Reves JG, Spinale FG. Aprotinin in cardiac surgery: a review of conventional and novel mechanisms of action. Anesth Analg 2007;105:949-62
48. Royston D. High dose aprotinin: a review of the first five years' experience. J Cardiothorac Vasc Anesth 1992;6:76-100
49. van Oeveren W, Jansen NJ, Bidstrup BP, Royston D, Westaby S, Neuhof H, Wildevuur CR. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg 1987;44:640-5
50. Chauhan S, Bisoi A, Modi R, Gharde P, Rajesh MR. Tranexamic acid in paediatric cardiac surgery. Indian J Med Res 2003;118:86-9
51. Rao BH, Saxena N, Chauhan S, Bisoi AK, Venugopal P. Epsilon aminocaproic acid in paediatric cardiac surgery to reduce postoperative blood loss. Indian J Med Res 2000;111:57-61
52. Bulutcu FS, Ozbek U, Polat B, Yalcin Y, Karaci AR, Bayindir O. Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? Paediatr Anaesth 2005;15:41-6
53. McClure PD, Izsak J. The use of epsilon-aminocaproic acid to reduce bleeding during cardiac bypass in children with congenital heart disease. Anesthesiology 1974;40:604-8
54. Zonis Z, Seear M, Reichert C, Sett S, Allen C. The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. J Thorac Cardiovasc Surg 1996;111:982-7
55. Levin E, Wu J, Devine DV, Alexander J, Reichart C, Sett S, Seear M. Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid. Thromb Haemost 2000;83:54-9
56. Williams GD, Bratton SL, Riley EC, Ramamoorthy C. Efficacy of epsilon-aminocaproic acid in children undergoing cardiac surgery. J Cardiothorac Vasc Anesth 1999;13:304-8
57. Urban AE, Popov-Cenic S, Noe G, Kulzer R. Aprotinin in open-heart surgery of infants and children using the heart-lung machine. Clin Ther 1984;6:425-33
58. Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin (trasylol). J Thorac Cardiovasc Surg 1989;97:364-72
59. Boldt J, Knothe C, Zickmann B, Wege N, Dapper F, Hempelmann G. Comparison of two aprotinin dosage regiments in pediatric patients having cardiac operations. J Thorac Cardiovasc Surg 1993;105:705-11
60. Boldt J, Zickmann B, Schindler E, Welters A, Dapper F, Hempelmann G. Influence of aprotinin on the thrombomodulin/protein c system in pediatric cardiac operations. J Thorac Cardiovasc Surg 1994;107:1215-21
61. Davies MJ, Allen A, Kort H, Weerasena NA, Rocco D, Paul CL, Hunt BJ, Elliott MJ. Prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations. Ann Thorac Surg 1997;63:497-503
62. D'Errico CC, Shayevitz JR, Martindale SJ, Mosca RS, Bove EL. The efficacy and cost of aprotinin in children undergoing reoperative open heart surgery. Anesth Analg 1996;83:1193-9
63. Dietrich W, Mossinger H, Spannagl M, Jochum M, Wendt P, Barankay A, Meisner H, Richter JA. Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations. J Thorac Cardiovasc Surg 1993;105:712-20
64. Herynkopf F, Lucchese F, Pereira E, Kalil R, Prates P, Nesralla IA. Aprotinin in children undergoing correction of congenital heart defects. A double-blind pilot study. J Thorac Cardiovasc Surg 1994;108:517-21
65. Huang H, Ding W, Su Z, Zhang W. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc Surg 1993;106:11-8
66. Miller BE, Tosone SR, Tam VK, Kanter KR, Guzzetta NA, Bailey JM, Levy JH. Hematologic and economic impact of aprotinin in reoperative pediatric cardiac operations. Ann Thorac Surg 1998;66:535-40, discussion 41
67. Seghaye CM, Duchateau J, Grabitz GR, Jablonka K, Wenzl T, Marcus C, Messmer JB, Bernuth G. Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children. Ann Thorac Surg 1996;61:1205-11
68. Wippermann CF, Schmid FX, Eberle B, Huth RG, Kampmann C, Schranz D, Oelert H. Reduced inotropic support after aprotinin therapy during pediatric cardiac operations. Ann Thorac Surg 1999;67:173-6
69. Arnold DM, Fergusson DA, Chan AK, Cook RJ, Fraser GA, Lim W, Blajchman MA, Cook DJ. Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin. Anesth Analg 2006;102:731-7
70. Mossinger H, Dietrich W. Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin dosage. Ann Thorac Surg 1998;65:S45-50; discussion S-1, S74-6
71. Carrel TP, Schwanda M, Vogt PR, Turina MI. Aprotinin in pediatric cardiac operations: a benefit in complex malformations and with high-dose regimen only. Ann Thorac Surg 1998;66:153-8
72. Costello JM, Backer CL, de Hoyos A, Binns HJ, Mavroudis C. Aprotinin reduces operative closure time and blood product use after pediatric bypass. Ann Thorac Surg 2003;75:1261-6
73. Boldt J, Schindler E, Knothe C, Hammerman H, Stertmann WA, Hempelmann G. Does aprotinin influence endothelial associated coagulation in cardiac surgery? J Cardiothorac Vasc Anesth 1994;8:527-31
74. Gurevitch J, Barak J, Hochhauser E, Paz Y, Yakirevich V. Aprotinin improves myocardial recovery after ischemia and reperfusion. Effects of the drug on isolated rat hearts. J Thorac Cardiovasc Surg 1994;108:109-18
75. Wendel HP, Heller W, Michel J, Mayer G, Ochsenfahrt C, Graeter U, Schulze J, Hoffmeister HM, Hoffmeister HE. Lower cardiac troponin t levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage. J Thorac Cardiovasc Surg 1995;109:1164-72
76. Tweddell J, Berger S, Frommelt CP, Pelech NA, Lewis AD, Fedderly TR, Frommelt AM, Mcmanus ST, Mussatto AK, Kessel WM, Litwin BS. Aprotinin improves outcome of single-ventricle palliation. Ann Thorac Surg 1996;62:1329-36
77. Hocker JR, Saving KL. Fatal aortic thrombosis in a neonate during infusion of epsilon-aminocaproic acid. J Pediatr Surg 1995;30:1490-2
78. Gruber EM, Shukla AC, Reid RW, Hickey PR, Hansen DD. Synthetic antifibrinolytics are not associated with an increased incidence of baffle fenestration closure after the modified fontan procedure. J Cardiothorac Vasc Anesth 2000;14:257-9
79. Downard CD, Betit P, Chang RW, Garza JJ, Arnold JH, Wilson JM. Impact of amicar on hemorrhagic complications of ecmo: a ten-year review. J Pediatr Surg 2003;38:1212-6
80. Winter SS, Chaffee S, Kahler SG, Graham ML. Epsilon-aminocaproic acid-associated myopathy in a child. J Pediatr Hematol Oncol 1995;17:53-5
81. Cosgrove 3rd D, Heric B, Lytle BW, Taylor PC, Novoa R, Golding LA, Stewart RW, McCarthy PM, Loop FD. Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. Ann Thorac Surg 1992;54:1031-6, discussion 6-8
82. Levy J, Pifarre R, Schaff H, Horrow J, Albus R, Speiss B, Rosengart T, Murray J, Clark R, Smith P. 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 1996;92:2236-44
83. Lemmer HJ, Staford W, Bonney LS, Breen FJ, Chomka VE, Eldredge JW, Holt WW, Karp BR, Laub WG, Lipton JM, Schaff VH, Tatooles JC, Rumberger AJ. Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. J Thorac Cardiovasc Surg 1994;107:543-53
84. Alderman EL, Levy JH, Rich JB, Nili M, Vidne B, Schaff H, Uretzky G, Pettersson G, Thiis JJ, Hantler CB, Chaitman B, Nadel A. 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
85. Poullis M, Manning R, Laffan M, Haskard DO, Taylor KM, Landis RC. The antithrombotic effect of aprotinin: actions mediated via the proteaseactivated receptor 1. J Thorac Cardiovasc Surg 2000;120:370-8
86. Petaja J, Peltola K. Venous thrombosis in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 1997;11:889-94
87. Moore RA, McNicholas KW, Naidech H, Flicker S, Gallagher JD. Clinically silent venous thrombosis following internal and external jugular central venous cannulation in pediatric cardiac patients. Anesthesiology 1985;62:640-3
88. Eaton MP, Alfieris GM. Hemispheric infarction in a patient with an undiagnosed vasculopathy treated with aprotinin. J Cardiothorac Vasc Anesth 2004;18:194-6
89. Heindel SW, Mill MR, Freid EB, Valley RD, White GC, 2nd, Norfleet EA. Fatal thrombosis associated with a hemi-fontan procedure, heparin-protamine reversal, and aprotinin. Anesthesiology 2001;94:369-71
90. Jaquiss RD, Ghanayem NS, Zacharisen MC, Mussatto KA, Tweddell JS, Litwin SB. Safety of aprotinin use and re-use in pediatric cardiothoracic surgery. Circulation 2002;106:I90-4
91. Despotis GJ, Alsoufiev A, Goodnough LT, Lappas DG. Aprotinin prolongs whole blood activated partial thromboplastin time but not whole blood prothrombin time in patients undergoing cardiac surgery. Anesth Analg 1995;81:919-24
92. Despotis GJ, Joist JH, Joiner-Maier D, Alsoufiev AL, Triantafillou AN, Goodnough LT, Santoro SA, Lappas DG. Effect of aprotinin on activated clotting time, whole blood and plasma heparin measurements. Ann Thorac Surg 1995;59:106-11
93. Guzzetta NA, Miller BE, Todd K, Szlam F, Moore RH, Tosone SR. An evaluation of the effects of a standard heparin dose on thrombin inhibition during cardiopulmonary bypass in neonates. Anesth Analg 2005;100:1276-82, table of contents
94. Guzzetta NA, Miller BE, Todd K, Szlam F, Moore RH, Brosius KK, Wilson EC, Cohen AM, Tosone SR. Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease. Anesth Analg 2006;103:1131-8
95. Habermann E, Arndts D, Just M, Raker KO, Torok P. Behavior of trasylol in the body as a model for the pharmacokinetics of basic polypeptides. Med Welt 1973;24:1163-7
96. Royston D, Levy JH, Fitch J, Dietrich W, Body SC, Murkin JM, Spiess BD, Nadel A. Full-dose aprotinin use in coronary artery bypass graft surgery: an analysis of perioperative pharmacotherapy and patient outcomes. Anesth Analg 2006;103:1082-8
97. Penkoske PA, Entwistle LM, Marchak BE, Seal RF, Gibb W. Aprotinin in children undergoing repair of congenital heart defects. Ann Thorac Surg 1995;60:S529-32
98. Ranucci M, Corno A, Pavesi M, Cirri S, Menicanti L, Frigiola A, Celoria R, Ditta A, Boncilli A, Conti D. Renal effects of low dose aprotinin in pediatric cardiac surgery. Minerva Anestesiol 1994;60:361-6
99. Hogue CW, London MJ. Aprotinin use during cardiac surgery: a new or continuing controversy? Anesth Analg 2006;103:1067-70
100. Dietrich W, Ebell A, Busley R, Boulesteix AL. Aprotinin and anaphylaxis: analysis of 12,403 exposures to aprotinin in cardiac surgery. Ann Thorac Surg 2007;84:1144-50
101. Dietrich W, Spath P, Zuhlsdorf M, Dalichau H, Kirchhoff PG, Kuppe H, Preiss DU, Mayer G. Anaphylactic reactions to aprotinin reexposure in cardiac surgery: relation to antiaprotinin immunoglobulin g and e antibodies. Anesthesiology 2001;95:64-71; discussion 5A-6A
102. Dietrich W, Spath P, Ebell A, Richter JA. Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight reexposures to aprotinin in heart operations. J Thorac Cardiovasc Surg 1997;113:194-201
103. Dietrich W. Incidence of hypersensitivity reactions. Ann Thorac Surg 1998;65:S60-4; discussion S74-6
104. Adkins B. Neonatal t cell function. J Pediatr Gastroenterol Nutr 2005;40(Suppl 1):S5-7
105. Bellanti JA, Zeliss BJ, Pung YH. Immunology of the fetus and newborn. In: Avery GB, Fletcher MA, MacDonald MG, eds. Neonatology: pathophysiology and management of the newborn. 5th ed. Philadelphia: Lippincott, Williams, and Wilkins, 1999:1105-9
106. Andersson U, Bird G, Britton S. Cellular mechanisms of restricted immunoglobulin formation in the human neonate. Eur J Immunol 1980;10:888-94
107. Beierlein W, Scheule AM, Dietrich W, Ziemer G. Forty years of clinical aprotinin use: a review of 124 hypersensitivity reactions. Ann Thorac Surg 2005;79:741-8
108. Ryckwaert Y, Barthelet Y, Bonnet-Boyer MC, Rochette A, Capdevila X, d'Athis F. Anaphylactic shock after a test-dose of aprotinin in pediatric orthopedic surgery.[see comment]. [french]. Ann Fr Anesth Reanim 1999;18:904-8
109. Cohen DM, Norberto J, Cartabuke R, Ryu G. Severe anaphylactic reaction after primary exposure to aprotinin. Ann Thorac Surg 1999;67:837- 8. See comment in Ann Thorac Surg 2000;69:1298
110. Bohrer H, Bach A, Fleischer F, Lang J. Adverse haemodynamic effects of high-dose aprotinin in a paediatric cardiac surgical patient. Anaesthesia 1990;45:853-4
111. Kaddoum RN, Chidiac EJ, Zestos MM, Rajan SD, Baraka A. An anaphylactic reaction after primary exposure to an aprotinin test dose in a child with a severe milk allergy. J Cardiothorac Vasc Anesth 2007;21:243-4
112. Wuthrich B, Schmid P, Schmid ER, Tornic M, Johansson SG. Ige-mediated anaphylactic reaction to aprotinin during anaesthesia. Lancet 1992;340:173-4
113. Longstaff C. Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents. Blood Coagul Fibrinolysis 1994;5:537-42
114. Vang SN, Stammers AH, Mejak BL, Rauch ED, Viessman TW, Bruda NL, Yang T. Co-administration of aprotinin and epsilon-aminocaproic acid during cardiopulmonary bypass in a swine model. J Extra Corpor Technol 2000;32:196-206
115. Ririe DG, James RL, O'Brien JJ, Lin YA, Bennett J, Barclay D, Hines MH, Butterworth JF. The pharmacokinetics of epsilon-aminocaproic acid in children undergoing surgical repair of congenital heart defects. Anesth Analg 2002;94:44-9, table of contents
116. Frederiksen MC, Bowsher DJ, Ruo TI, Henthorn TK, Ts'ao CH, Green D, Atkinson AJ Jr. Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects. Clin Pharmacol Ther 1984;35:387-93
117. Butterworth J, James RL, Lin Y, Prielipp RC, Hudspeth AS. Pharmacokinetics of epsilon-aminocaproic acid in patients undergoing aortocoronary bypass surgery. Anesthesiology 1999;90:1624-35
118. Murphy BA, Ririe DG, James RL, Butterworth JF. Simulated serum concentrations of tranexamic acid (ta) with clinically used dosing regimens in children during repair of congenital heart defects. Anesthesiology 2001;95:A1267
119. Oliver WC Jr, Fass DN, Nuttall GA, Dearani JA, Schrader LM, Schroeder DR, Ereth MH, Puga FJ. Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 2004;127:1670-7
120. Hazan E, Pasaoglu I, Demircin M, Bozer AY. The effect of aprotinin (trasylol) on postoperative bleeding in cyanotic congenital heart disease. Turk J Pediatr 1991;33:99-109
121. Martin Burcio S, Valino Gonzalez J, Dominguez F, Diaz Balda J, Martinez M, Vellibre D. Use of aprotinin during pediatric heart surgery. Rev Esp Anestesiol Reanim 2001;48:212-6