Pediatric Cardiology

, Volume 33, Issue 2, pp 280–285 | Cite as

Plasmin Generation and Fibrinolysis in Pediatric Patients Undergoing Cardiopulmonary Bypass Surgery

  • Vera Ignjatovic
  • Aparajith Chandramouli
  • Jenny Than
  • Robyn Summerhayes
  • Fiona Newall
  • Steve Horton
  • Andrew Cochrane
  • Paul Monagle
Original Article
First Online:
Received:
Accepted:

Abstract

This prospective, single-centre cohort study aimed to evaluate plasmin generation and fibrinolysis during and after cardiopulmonary bypass (CPB) surgery in a cohort of children up to 6 years of age. Blood samples were drawn at eight time points: after induction of anesthesia, before unfractionated heparin (UFH), after UFH, after initiation of bypass, before protamine, after protamine, after chest closure, and 6 h after chest closure. The study identified an increase in fibrinolysis during CPB and particularly up to 6 h afterward in children. This could be the mechanism for the significant bleeding events observed in this young population after CPB. This study establishes the foundation for future studies in this area, particularly those focusing on clinical outcomes after CPB surgery.

Keywords

Cardiopulmonary bypass, children CPB Fibrin monomers Fibrinolysis Plasmin 
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References

  1. 1.
    Andrew M, Paes B, Johnston M (1990) Development of the hemostatic system in the neonate and young infant. Blood 12:95–104Google Scholar
  2. 2.
    Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM et al (1987) Development of the human coagulation system in the full-term infant. Blood 70:165–172PubMedGoogle Scholar
  3. 3.
    Bouma BN, Mosnier LO (2006) Thrombin activatable fibrinolysis inhibitor (TAFI): How does thrombin regulate fibrinolysis? Ann Med 38:378–388PubMedCrossRefGoogle Scholar
  4. 4.
    Chan AK, Leaker M, Burrows FA, Williams WG, Gruenwald CE, Whyte L, Adams M, Brooker LA, Adams H, Mitchell L, Andrew M (1997) Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost 77:270–277PubMedGoogle Scholar
  5. 5.
    Chandler WL (2005) Effects of hemodilution, blood loss, and consumption on hemostatic factor levels during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 19:459–467PubMedCrossRefGoogle Scholar
  6. 6.
    Corrigan JJ Jr, Sleeth JJ, Jeter M, Lox CD (1989) Newborn’s fibrinolytic mechanism: components and plasmin generation. Am J Hematol 32:273–278PubMedCrossRefGoogle Scholar
  7. 7.
    Davies LK (1999) Cardiopulmonary bypass in infants and children: How is it different? J Cardiothorac Vasc Anesth 13:330–345PubMedCrossRefGoogle Scholar
  8. 8.
    Dietrich W, Dilthey G, Spannagl M, Jochum M, Braun SL, Richter JA (1995) 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 83:679–689PubMedCrossRefGoogle Scholar
  9. 9.
    Eisses MJ, Seidel K, Aldea GS, Chandler WL (2004) Reducing hemostatic activation during cardiopulmonary bypass: a combined approach. Anesth Analg 98:1208–1216PubMedCrossRefGoogle Scholar
  10. 10.
    Guay J, Rivard GE (1996) Mediastinal bleeding after cardiopulmonary bypass in pediatric patients. Ann Thorac Surg 62:1955–1960PubMedCrossRefGoogle Scholar
  11. 11.
    Hunt B, Parratt RN, Segal HC, Sheikh S, Kallis P, Yacoub M (1998) Activation of coagulation and fibrinolysis during cardiothoracic operations. Ann Thorac Surg 65:712–718PubMedCrossRefGoogle Scholar
  12. 12.
    Ignjatovic V, Than J, Summerhayes R, Newall F, Horton S, Cochrane A, Monagle P (2011) Hemostatic response in paediatric patients undergoing cardiopulmonary bypass surgery. Ped Cardiol 32(5):621–627CrossRefGoogle Scholar
  13. 13.
    Khuri SF, Valeri CR, Loscalzo J, Weinstein MJ, Birjiniuk V, Healey NA, MacGregor H, Doursounian M, Zolkewitz MA (1995) Heparin causes platelet dysfunction and induces fibrinolysis before cardiopulmonary bypass. Ann Thorac Surg 60:1008–1014PubMedCrossRefGoogle Scholar
  14. 14.
    Levi M, Cromheecke ME, de Jonge E, Prins MH, de Mol BJ, Briët E, Buller HR (1999) Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 354:1940–1947PubMedCrossRefGoogle Scholar
  15. 15.
    Mossinger H, Dietrich W (1998) Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin dosage. Ann Thorac Surg 65(6 Suppl):S45–S50PubMedCrossRefGoogle Scholar
  16. 16.
    Mossinger H, Dietrich W, Braun SL, Jochum M, Meisner H, Richter JA (2003) High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery. Ann Thorac Surg 75:430–437PubMedCrossRefGoogle Scholar
  17. 17.
    Parmar N, Mitchell LG, Berry LR, Andrew M, Chan AK (2006) The influence of age on in vitro plasmin generation in the presence of fibrin monomer. Acta Haematol 115:141–151PubMedCrossRefGoogle Scholar
  18. 18.
    Parmar N, Albisetti M, Berry LR, Chan AK (2006) The fibrinolytic system in newborns and children. Clin Lab 52:115–124PubMedGoogle Scholar
  19. 19.
    Parmar N, Mitchell LG, Berry LR, Andrew M, Chan AK (2006) The influence of age on in vitro plasmin generation in the presence of fibrin monomer. Acta Haematol 115:141–151PubMedCrossRefGoogle Scholar
  20. 20.
    Ray MJ, Marsh NA, Hawson GA (1994) Relationship of fibrinolysis and platelet function to bleeding after cardiopulmonary bypass. Blood Coagul Fibrinolysis 5:679–685PubMedCrossRefGoogle Scholar
  21. 21.
    Summerhayes R, Ignjatovic V, Hall M, Monagle P (2007) Age-related reference ranges for TAFI and fibrin monomers in healthy children. J Throm Haemost 5(Suppl 2):P-S-397Google Scholar
  22. 22.
    Teufelsbauer H, Proidl S, Havel M, Vukovich T (1992) Early activation of hemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis. Thromb Haemost 68:250–252PubMedGoogle Scholar
  23. 23.
    Valen G, Eriksson E, Risberg B, Vaage J (1994) Fibrinolysis during cardiac surgery: release of tissue plasminogen activator in arterial and coronary sinus blood. Eur J Cardiothorac Surg 8:324–330PubMedCrossRefGoogle Scholar
  24. 24.
    Williams GD, Bratton SL, Ramamoorthy C (1999) Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open heart surgery. Anesth Analg 89:57–64PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Vera Ignjatovic
    • 1
    • 2
  • Aparajith Chandramouli
    • 3
  • Jenny Than
    • 3
  • Robyn Summerhayes
    • 1
    • 2
  • Fiona Newall
    • 1
    • 2
    • 3
    • 4
  • Steve Horton
    • 5
  • Andrew Cochrane
    • 2
    • 6
  • Paul Monagle
    • 1
    • 2
    • 3
  1. 1.Murdoch Childrens Research InstituteParkvilleAustralia
  2. 2.Department of PaediatricsThe University of MelbourneMelbourneAustralia
  3. 3.Department of Clinical HaematologyRoyal Children’s HospitalMelbourneAustralia
  4. 4.Department of NursingThe University of MelbourneMelbourneAustralia
  5. 5.Department of Cardiac SurgeryRoyal Children’s HospitalMelbourneAustralia
  6. 6.Department of Cardiothoracic SurgeryMonash Medical CentreMelbourneAustralia

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