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Thromb Haemost 1997; 77(02): 270-277
DOI: 10.1055/s-0038-1655952
Original Article
Schattauer GmbH Stuttgart

Coagulation and Fibrinolytic Profile of Paediatric Patients Undergoing Cardiopulmonary Bypass

Anthony K C Chan
1   The Research Institute, McMaster University, Hamilton, Ontario, Canada
,
Michael Leaker
7   The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
,
Frederick A Burrows
2   Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada
5   Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
,
William G Williams
3   Department of Cardiovascular Surgery, McMaster University, Hamilton, Ontario, Canada
,
Colleen E Gruenwald
6   Department of Cardiovascular Perfusion, The Hospital for Sick Children, Toronto, Canada
,
Linda Whyte
2   Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada
,
Margaret Adams
4   Department of Haematology/Oncology, McMaster University, Hamilton, Ontario, Canada
,
Lu Ann Brooker
7   The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
,
Helen Adams
4   Department of Haematology/Oncology, McMaster University, Hamilton, Ontario, Canada
,
Lesley Mitchell
7   The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
,
Maureen Andrew
4   Department of Haematology/Oncology, McMaster University, Hamilton, Ontario, Canada
7   The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
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Publikationsverlauf

Received 06. September 1995

Accepted after revision 17. Oktober 1996

Publikationsdatum:
10. Juli 2018 (online)

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Summary

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XI, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, α2-macroglobulin, plasminogen, α2-antiplas- min, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, α2AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (<2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

 

  • References

  • 1 Andrew M, MacIntyre B, Williams W, Gruenwald C, Johnston M, Burrows F, Wang E, MacMillan J, Adams M. Heparin therapy during cardiopulmonary bypass requires ongoing quality control. Thromb Haemost 1993; 70 (06) 937-941
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 2 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 76: 1680-1697
    PubMedGoogle Scholar
  • 3 Mammen EF, Koets MH, Washington BC, Wolk LW, Brown JM, Burdick M, Selik N, Wilson RF. Hemostasis changes during cardiopulmonary bypass surgery. Semin Thromb Hemost 1985; 11: 281-292
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 4 Bick RL. Hemostasis defects associated with cardiac surgery prosthetic devicesand other extracorporeal circuits. Seminars in Thromb Hemost 1985; 11: 249-280
    PubMedGoogle Scholar
  • 5 Gruenwald C, Andrew M, Burrows F. et al. Advances in cardiac surgery. 4. Mosby-Year Book Inc. 1993. Cardiopulmonary bypass in the neonate pp 137-156
    Google Scholar
  • 6 Turner-Gomes S, Nitschmann E, Andrew M. et al. Additional heparin affects thrombin generation during cardiopulmonary bypass surgery for congenital heart disease. Thromb Haemost 1993; 69 (06) 1167 (Abstract 2237)
    PubMedGoogle Scholar
  • 7 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen D, Powers P. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
    CrossrefPubMedGoogle Scholar
  • 8 Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 1990; 12: 095-104
    CrossrefPubMedGoogle Scholar
  • 9 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80 (08) 1998-2005
    CrossrefPubMedGoogle Scholar
  • 10 Klaus A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogen. Acta Haematol 1957; 17: 287
    CrossrefPubMedGoogle Scholar
  • 11 Kluft C. Determination of prekallikrein in human plasma: Optimal conditions for activating prekallikrein. J Lab Clin Med 1978; 91: 83-95
    PubMedGoogle Scholar
  • 12 Mancini G, Carbonara O, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. J Immunochem 1965; 02: 235-254
    CrossrefPubMedGoogle Scholar
  • 13 Kahle L, Schipper H, Jenkins C, ten Cate J, Antithrombin III. Evaluation of an automated method. Thromb Res 1978; 12: 1003
    CrossrefPubMedGoogle Scholar
  • 14 Vestergaard L. The titration of heparin with protamine. Scand J Clin Lab Invest 1954; 06: 284-287
    CrossrefPubMedGoogle Scholar
  • 15 Andrew M, Castle V, Mitchell L, Paes B. A modified bleeding time in the infant. Am J Hematol 1989; 30: 190-191
    CrossrefPubMedGoogle Scholar
  • 16 Andrew M, Mitchell L, Vegh P, Ofosu F. Thrombin regulation in children differs from adults in the absence and presence of heparin. Thromb Haemost 1994; 72 (06) 836-842
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Komp DM, Sparrow AW. Polycythemia in cyanotic heart disease — a study of altered coagulation. J Pediatr 1970; 76: 231-236
    CrossrefPubMedGoogle Scholar
  • 18 Inenacho HNC, Breeze GR, Fletcher DJ, Stuart J. Consumption coagulopathy in congenital heart disease. Lancet 1973; 1: 231-234
    PubMedGoogle Scholar
  • 19 Iolster NJ. Blood coagulation in children with cyanotic congenital heart disease. Acta Paediatr Scand 1970; 59: 551-557
    CrossrefPubMedGoogle Scholar
  • 20 Johnson CA, Abildgaard CF, Schulman I. Absence of coagulation abnormalities in children with cyanotic congenital heart disease. Lancet 1968; 02: 660-662
    PubMedGoogle Scholar
  • 21 Waldman JD, Czapek EE, Paul MH, Schwartz AD, Levin DL, Schindler S. Shortened platelet survival in cyanotic heart disease. J Pediatr 1975; 87: 77-79
    CrossrefPubMedGoogle Scholar
  • 22 Tanaka K, Wada K, Morimoto T, Shomura S, Satoh T, Yada I, Yuasa H, Kusagawa M, Deguchi K. The role of the protein C-thrombomodulin system in physiologic anticoagulation during cardiopulmonary bypass. ASAIO Transactions 1989; 35: 373-375
    CrossrefPubMedGoogle Scholar
  • 23 Kern FH, Morana NJ, Seras JJ, Hickey PR. Coagulation Defects in Neonates During Cardiopulmonary Bypass. Ann Thorac Surg 1992; 54: 541-546
    CrossrefPubMedGoogle Scholar
  • 24 Gruenwald C. Neonatal prime composition and rationale at the Hospital for Sick Children. Proc Am Acad Cardio Perf 1994; 15 (Jan) 48-51
    PubMedGoogle Scholar
  • 25 Mammen E. Factor V deficiency. Semin Thromb Haemost 1983; 09: 17-18
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 26 Mammen E, Murano G, Bick R. Factor VIII abnormalities. Semin Thromb Haemost 1983; 09 (01) 22-27
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 27 Boisclair MD, Lane DA, Philippou H, Sheikh S, Hunt B. Thrombin production inactivation and expression during open heart surgery measured by assays for activation fragments including a new ELISA for prothrombin fragment Fl+2. Thromb Haemost 1993; 70 (02) 253-258
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 Boldt J, Schindler E, Knothe C, Hammermann H, Stertmann WA, Hempel-mann G. Does Aprotinin Influence Endothelial-Associated Coagulation in Cardiac Surgery?. J Cardiothorac Vasc Anesth 1994; 08: 527-531
    CrossrefPubMedGoogle Scholar
  • 29 Tumer-Gomes S, Mitchell L, Williams W, Andrew M. Thrombin regulation in congenital heart disease following cardiopulmonary bypass surgery. J Thorac Cardiovasc Surg 1994; 107: 562-568
    PubMedGoogle Scholar
  • 30 Broze GJ, Miletich J, Colman R, Hirsh J, Marder V, Salzman E. editors Hemostasis and Thrombosis. Basic Principles and Clinical Practice. 03. Philadelphia: J.B Lippincott; 1994: 13Biochemistry and physiology of protein C, protein S, and thrombomodulin. pp. 259-276
    Google Scholar
  • 31 Páramo JA, Rifon J, Lloren R, Casares J, Paloma MJ, Rocha E. Intra-and Postoperative Fibrinolysis in Patients Undergoing Cardiopulmonary Bypass Surgery. Haemostasis 1991; 21: 58-64
    PubMedGoogle Scholar
  • 32 Tanaka K, Takao M, Yada I, Yuasa H, Kusagawa M, Deguchi K. Alterations in coagulation and fibrinolysis associated with cardiopulmonary bypass during open heart surgery. Journal of Cardiothoracic Anesthesia 1989; 03 (02) 181-188
    CrossrefPubMedGoogle Scholar
  • 33 Spiess BD. The Contribution of Fibrinolysis to Postbypass Bleeding. J Cardiothorac Vasc Anesth 1991; 05 (06) (Suppl. 01) 13-17
    CrossrefPubMedGoogle Scholar
  • 34 Royston D. Aprotinin Prevents Bleeding and Has Effects on Platelets and Fibrinolysis. J Cardiothorac Vase Anesth 1991; 05 (06) (Suppl. 01) 18-23
    CrossrefPubMedGoogle Scholar
  • 35 Dietrich W, Spannagl M, Schramm W, Vogt W, Barankay A, Richter J. The influence of preoperative anticoagulation on heparin response during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1991; 102: 505-514
    PubMedGoogle Scholar
  • 36 Dietrich W, Schroll A, Gob E, Barankay A, Richter JA. Improved heparin response by substitution of antithrombin III concentrate during extracorpo-real circulation. Der Anaesthesist 1984; 33: 422-427
    PubMedGoogle Scholar
  • 37 Hogg P, Jackson C. Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: Implications for heparin efficacy. Proc Natl Acad Sci USA 1989; 86: 3619-3623
    CrossrefPubMedGoogle Scholar
  • 38 Weitz J, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III independent inhibitors. J Clin Invest 1990; 86: 385-391
    CrossrefPubMedGoogle Scholar
  • 39 Levine MN, Hirsh J. Hemorrhagic complications of anticoagulant therapy. Semin Thromb Haemost 1986; 12: 39-57
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 40 Jumean HG, Sudah F. Monitoring of anticoagulant therapy during open-heart surgery in children with congenital heart disease. Acta Haematol 1983; 70: 392-395
    CrossrefPubMedGoogle Scholar
  • 41 von SegesserL, Weiss B, Garcia E, Gallino A, Turina M. Reduced blood loss and transfusion requirements with low systemic heparinization: preliminary clinical results in coronary artery revascularization. Eur J Cardiothorac Surg 1990; 04: 639-543
    CrossrefPubMedGoogle Scholar
  • 42 Babka R, Colby C, El-Etr A, Pifarre R. Monitoring of intraoperative heparinization and blood loss following cardiopulmonary bypass surgery. J Thorac Cardiovasc Surg 1977; 73 (05) 780-782
    PubMedGoogle Scholar
  • 43 Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 1975; 69: 685-688
    PubMedGoogle Scholar
  • 44 Bull BS, Korpman RA, Huse WM, Briggs BD. Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 1975; 69: 674-684
    CrossrefPubMedGoogle Scholar
  • 45 Young JA, Kisker CT, Doty DB. Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer. Ann Thorac Surg 1978; 26: 231-240
    CrossrefPubMedGoogle Scholar
  • 46 Culliford AT, Gitel SN, Starr N, Thomas ST, Baumann FG, Wessler S, Spencer FC. Lack of correlation between activated clotting time and plasma heparin during cardiopulmonary bypass. Ann Surg 1980; 193: 105-111
    PubMedGoogle Scholar
  • 47 Bode A, Lust RM. Masking of heparin activity in the activated coagulation time (ACT) by platelet procoagulant activity. Thromb Res 1994; 73 (05) 285-300
    CrossrefPubMedGoogle Scholar
  • 48 Ellison N, Edmunds LH, Colman RW. Platelet aggregation following heparin and protamine administration. Anesthesiology 1994; 48: 65-68
    PubMedGoogle Scholar
  • 49 Carr MJ, Carr S. At High Heparin Concentrations Protamine Concentrations which Reverse Heparin Anticoagulant Effects Are Insufficient to Reverse Heparin Anti-platelet Effects. Thromb Res 1994; 75 (06) 617-630
    CrossrefPubMedGoogle Scholar
  • 50 Hirsh J, Salzman EW, Marder VJ, Colman RW, Hirsh J, Marder VJ, Salz-man EW. eds Hemostasis and Thrombosis – Basic Principles and Clinical Practice. 03. ed. J.P Lippincott Company; 1994. 69 Treatment of Venous Thromboembolism pp 1346-1366
    Google Scholar
  • 51 Andrew M, Marzinotto V, Blanchette V, Ginsberg J, Burrows P, Benson L, Williams W, David M, Poon A, Sparling C. Heparin therapy in pediatric patients: A prospective cohort study. Pediatr Res 1994; 35: 78-83
    CrossrefPubMedGoogle Scholar
  • 52 Hirsh J, Heparin N, Engl J Med. 1991; 324 (22) 1565-1574
    PubMed
  • 53 Harker LA, Malpass TW, Branson HE, Hessel EA, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: Acquired transient platelet dysfunction associated with selective granule release. Blood 1980; 56: 824-834
    PubMedGoogle Scholar
  • 54 Fedderick WCampbell. The contribution of platelet dysfunction to postbypass bleeding. J Cardiothorac Vase Anesth 1991; 05 (06) (Suppl. 01) 08-12
    CrossrefPubMedGoogle Scholar