Orthopedics, 2013;27(6):S653–S658
Cite this articlePublished Online:June 02, 2004https://doi.org/10.3928/0147-7447-20040602-05Cited by:20
Abstract
abstract
Aprotinin is a polypeptide with serine protease inhibitory activity of key enzymes associated with inflammatory, fibrinolytic, and hemostatic pathways. The drug binds directly to the fibrinolytic plasmin at the lower plasmin-inhibiting dose (plasma concentration, 137 KlU/mL), and the inflammatory mediator, kallikrein, using the higher kallikrein-inhibiting dose (plasma concentration, >250 KlU/mL). Aprotinin inhibits platelet glycoprotein loss (GpIb and Gpllb/llla receptors) associated with cardiopulmonary bypass and has been described as platelet sparing. Current literature supports direct anti-inflammatory effects through modulation of neutrophil activation, attachment, and transmigration, with resultant blunting in the rise of proinflammatory cytokine levels and deleterious tissue damaging enzymes. The pharmacologic properties of aprotinin may lead clinicians to consider this therapy for use as a hemostatic and anti-inflammatory agent in surgeries beyond its established use in coronary artery bypass graft surgery.
- 1. RoystOD D, Bidstrup BP, Taylor KM. Sapsford RN. Effect of aprotinin on need for blood transfusion after repeal open-heart surgery. Lancet. 1987: 2:1289-1291. > Google Scholar
- 2. Aprotinin (Trasylol, aprotinin injection) package insert. Bayer Corporation. West Haven, Conn. March 2(X)I . > Google Scholar
- 3. Fritz H. Wunderer G. Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. Arzneimittelfbrschung. 1983: 33:479-494. > Google Scholar
- 4. Peters DC. Noble S. Aprotinin: an update of its pharmacology and therapeutic use in open heart surgery and coronary artery bypass surgery. Drugs. 1999; 57:233-260. > Google Scholar
- 5. Royston D. Preventing the inflammatory response to open-heart surgery: the role of aprotinin and other protease inhibitors, hit J Cardiol. 1996; 53(Suppl):Sl 1-S37. > Google Scholar
- 6. 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; 72:438-443. > Google Scholar
- 7. Mastroroberto P. Chello M, Zofrea S. Marchese AR. Suppressed fibrinolysis after administration of low-dose aprotinin: reduced level of plasmin-alpha2-plasmin inhibitor complexes and postoperative blood loss. Eur J Cardiothorac Surg. 1995: 9:143145. > Google Scholar
- 8. Van Oeveren W. Jansen NJ. Bidstrup BP. et al. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thome Surg. 1987:44:640-645. > Google Scholar
- 9. Blauhut B, Gross C, Necek S. Doran JE, Spath P, Lundsgaard-Hansen P. Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass. J Thome Cardiovasc Surg. 1991; 101:958967. > Google Scholar
- 10. Van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CR. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thome Cardiovasc Surg. 1990; 99:788-796: discussion 796-787. > Google Scholar
- 1 1 . Primack C, Walenga JM. Koza MJ, Shankey TV, Pifarre R. Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass operations. Ann Thome Surg. 1996: 61 : 1 188-1 193. > Google Scholar
- 12. Lavee J, Savion N, Smolensky A, Goor DA. Mohr R. Platelet protection by aprotinin in cardiopulmonary bypass: electron microscopic study. Ann Thome Surg. 1992: 53:477-481. > Google Scholar
- 13. Poullis M, Manning R, Laffan M. Haskard DO. Taylor KM, Landis RC. The antidirombotic effect of aprotinin: actions mediated via the proteaseacti vated receptor 1. J Thome Cardiovasc Surg. 2000; 120:370-378. > Google Scholar
- 1 4. Kamiya T. Katayama Y, Kashi wagi F. Terashi A. The role of bradykinin in mediating ischemic brain edema in rats. Stinke. 1993: 24:571-575: discussion 575-576. > Google Scholar
- 15. Asimakopoulos G, Thompson R, Nourshargh S. et al. An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation. J Thorac Cardiovasc Surg. 2000; 120:361-369. > Google Scholar
- 16. Hill GE, Pohorecki R. Alonso A. Rennard Sl. Robbins RA. Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass. Anesth Analg. 1996; 83:696-700. > Google Scholar
- 17. Whitten CVV. Latson TW. Allison PM. Levy JH, Salmenpera MT, Oflaherty DN. Does aprotinin inhibit cardiopulmonary bypassinduced inflammation? Anesthesiology. 1992:77:A266. > Google Scholar
- 18. Stammers AH. Huffman S, Alonso A. el al. The antiinflammatory effects of aprotinin in patients undergoing cardiac surgery with cardiopulmonary bypass. J Extra Corpor Techno!. 1997:29:114-122. > Google Scholar
- 19. Rahman A. Usiunda B. Burma O, Ozercan IH, Cekirdekci A. Bayar MK. Does aprotinin reduce lung reperfusion damage after cardiopulmonary bypass? Eur J Cardiothorac Surg. 2000: 18:583-588. > Google Scholar
- 20. Himmelfarb J. Holbrook D. McMonagle E. Effects of aprotinin on complement and granulocyte activation during ex vivo hemodialysis. Am J Kidney Dis. 1994; 24:901-906. > Google Scholar
- 21. Wendel HP, Heller W. Michel J, et al. 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: J 09: J 164-1 172. > Google Scholar
- 22. Hill GE, Robbins RA. Aprotinin but not tranexamic acid inhibits cytokine-induced inducible nitric oxide synthase expression. Anesth Analg. 1 997: 84: 1 1 98- 1 202. > Google Scholar
- 23. Dietrich W. Incidence of hypersensitivity reactions. Ann Thorac Surg. 1998: 65:S60S64; discussion S74-S66. > Google Scholar
- 24. Lemmer JH Jr, Stanford W, Bonney SL. et al. Aprotinin for coronary artery bypass grafting: effect on postoperative renal function. Ann Thorac Surg. 1995: 59:132-136. > Google Scholar
