Subscribe to RSS
DOI: 10.1160/TH06-12-0723
Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin
Publication History
Received
18 December 2006
Accepted after resubmission
11 May 2007
Publication Date:
28 November 2017 (online)
Summary
Platelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB.Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]),weighting less than 15 kg and undergoing normothermic CPB (35–36°C) were randomly assigned to two equal groups,one of which received high-dose aprotinin.Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1+2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated αIIbβ3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1+2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression afterTRAP activation (p=0.05).This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.
-
References
- 1 Harker LA, Malpass TW, Branson HE. et al. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood 1980; 56: 824-834.
- 2 Rinder CS, Gaal D, Student LA. et al. Platelet-leukocyte activation and modulation of adhesion receptors in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994; 107: 280-288.
- 3 Hezard N, Potron G, Schlegel N. et al. Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children. Thromb Haemost 2003; 90: 116-123.
- 4 Ichinose F, Uezono S, Muto R. et al. Platelet hyporeactivity in young infants during cardiopulmonary bypass. Anesth Analg 1999; 88: 258-262.
- 5 Levi M, Cromheecke ME, de Jonge E. et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999; 354: 1940-1947.
- 6 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: 11-18.
- 7 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: 370-378.
- 8 Kozek-Langenecker SA, Mohammad SF, Masaki T. et al. The effects of aprotonin on platelets in vitro using whole blood flow cytometry. Anesth Analg 2000; 90: 12-16.
- 9 Bradfield JF, Bode AP. Aprotinin restores the adhesive capacity of dysfunctional platelets. Thromb Res 2003; 109: 181-188.
- 10 Day JR, Punjabi PP, Randi AM. et al. Clinical inhibition of the seven-transmembrane thrombin receptor (PAR1) by intravenous aprotinin during cardiothoracic surgery. Circulation 2004; 110: 2597-2600.
- 11 Poullis M, Landis RC, Taylor KM. Aprotinin: is it prothrombotic?. Perfusion 2001; 16: 401-409.
- 12 Wildevuur CR, Eijsman L, Roozendaal KJ. et al. Platelet preservation during cardiopulmonary bypass with aprotinin. Eur J Cardiothorac Surg 1989; 3: 533-537 discussion 537–538.
- 13 Mossinger H, Dietrich W, Braun SL. et al. Highdose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery. Ann Thorac Surg 2003; 75: 430-437.
- 14 Speziale G, Ferroni P, Ruvolo G. et al. Effect of normothermic versus hypothermic cardiopulmonary bypass on cytokine production and platelet function. J Cardiovasc Surg (Torino) 2000; 41: 819-827.
- 15 Royston D. High-dose aprotinin therapy: a review of the first five years’ experience. J Cardiothorac Vasc Anesth 1992; 6: 76-100.
- 16 Khairy M, Lasne D, Brohard-Bohn B. et al. A new approach in the study of the molecular and cellular events implicated in heparin-induced thrombocytopenia. Formation of leukocyte-platelet aggregates. Thromb Haemost 2001; 85: 1090-1096.
- 17 Guay J, Ruest P, Lortie L. Cardiopulmonary bypass induces significant platelet activation in children undergoing open-heart surgery. Eur J Anaesthesiol 2004; 21: 953-956.
- 18 Nurden A, Cazes E, Bihour C. et al. Confirmation that GP Ib-IX complexes have a reduced surface distribution on platelets activated by thrombin and TRAP-14-mer peptide. Br J Haematol 1995; 90: 645-654.
- 19 van Oeveren W, Harder MP, Roozendaal KJ. et al. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990; 99: 788-796 discussion 796–797.
- 20 Boldt J, Knothe C, Zickmann B. et al. Platelet function in cardiac surgery: influence of temperature and aprotinin. Ann Thorac Surg 1993; 55: 652-658.
- 21 Jonas RA, Wypij D, Roth SJ. et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg 2003; 126: 1765-1774.
- 22 D’Errico CC, Munro HM, Bove EL. Pro: the routine use of aprotinin during pediatric cardiac surgery is a benefit. J Cardiothorac Vasc Anesth 1999; 13: 782-784.
- 23 Williams GD, Ramamoorthy C. Con: the routine use of aprotinin during pediatric cardiac surgery is not a benefit. J Cardiothorac Vasc Anesth 1999; 13: 785-788.
- 24 Arnold DM, Fergusson DA, Chan AK. et al. Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin. Anesth Analg 2006; 102: 731-737.
- 25 Costello JM, Backer CL, de Hoyos A. et al. Aprotinin reduces operative closure time and blood product use after pediatric bypass. Ann Thorac Surg 2003; 75: 1261-1266.
- 26 Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354: 353-365.
- 27 Karkouti K, Beattie WS, Dattilo KM. et al. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006; 46: 327-338.