Coagulation and Fibrinolytic Profile of Paediatric Patients Undergoing Cardiopulmonary Bypass

Anthony K C Chan; Michael Leaker; Frederick A Burrows; William G Williams; Colleen E Gruenwald; Linda Whyte; Margaret Adams; Lu Ann Brooker; Helen Adams; Lesley Mitchell; Maureen Andrew

doi:10.1055/s-0038-1655952

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

Autoren

Anthony K C Chan

¹The Research Institute, McMaster University, Hamilton, Ontario, Canada
Michael Leaker

⁷The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
Frederick A Burrows

²Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada

⁵Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
William G Williams

³Department of Cardiovascular Surgery, McMaster University, Hamilton, Ontario, Canada
Colleen E Gruenwald

⁶Department of Cardiovascular Perfusion, The Hospital for Sick Children, Toronto, Canada
Linda Whyte

²Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada
Margaret Adams

⁴Department of Haematology/Oncology, McMaster University, Hamilton, Ontario, Canada
Lu Ann Brooker

⁷The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
Helen Adams

⁴Department of Haematology/Oncology, McMaster University, Hamilton, Ontario, Canada
Lesley Mitchell

⁷The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
Maureen Andrew

⁴Department of Haematology/Oncology, McMaster University, Hamilton, Ontario, Canada

⁷The Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada

Abstract

als PDF herunterladen

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.

PDF (598 kb)

Referenzen

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
2 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 76: 1680-1697
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
4 Bick RL. Hemostasis defects associated with cardiac surgery prosthetic devicesand other extracorporeal circuits. Seminars in Thromb Hemost 1985; 11: 249-280
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
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)
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
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
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
10 Klaus A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogen. Acta Haematol 1957; 17: 287
11 Kluft C. Determination of prekallikrein in human plasma: Optimal conditions for activating prekallikrein. J Lab Clin Med 1978; 91: 83-95
12 Mancini G, Carbonara O, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. J Immunochem 1965; 02: 235-254
13 Kahle L, Schipper H, Jenkins C, ten Cate J, Antithrombin III. Evaluation of an automated method. Thromb Res 1978; 12: 1003
14 Vestergaard L. The titration of heparin with protamine. Scand J Clin Lab Invest 1954; 06: 284-287
15 Andrew M, Castle V, Mitchell L, Paes B. A modified bleeding time in the infant. Am J Hematol 1989; 30: 190-191
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
17 Komp DM, Sparrow AW. Polycythemia in cyanotic heart disease — a study of altered coagulation. J Pediatr 1970; 76: 231-236
18 Inenacho HNC, Breeze GR, Fletcher DJ, Stuart J. Consumption coagulopathy in congenital heart disease. Lancet 1973; 1: 231-234
19 Iolster NJ. Blood coagulation in children with cyanotic congenital heart disease. Acta Paediatr Scand 1970; 59: 551-557
20 Johnson CA, Abildgaard CF, Schulman I. Absence of coagulation abnormalities in children with cyanotic congenital heart disease. Lancet 1968; 02: 660-662
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
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
23 Kern FH, Morana NJ, Seras JJ, Hickey PR. Coagulation Defects in Neonates During Cardiopulmonary Bypass. Ann Thorac Surg 1992; 54: 541-546
24 Gruenwald C. Neonatal prime composition and rationale at the Hospital for Sick Children. Proc Am Acad Cardio Perf 1994; 15 (Jan) 48-51
25 Mammen E. Factor V deficiency. Semin Thromb Haemost 1983; 09: 17-18
26 Mammen E, Murano G, Bick R. Factor VIII abnormalities. Semin Thromb Haemost 1983; 09 (01) 22-27
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
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
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
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
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
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
33 Spiess BD. The Contribution of Fibrinolysis to Postbypass Bleeding. J Cardiothorac Vasc Anesth 1991; 05 (06) (Suppl. 01) 13-17
34 Royston D. Aprotinin Prevents Bleeding and Has Effects on Platelets and Fibrinolysis. J Cardiothorac Vase Anesth 1991; 05 (06) (Suppl. 01) 18-23
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
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
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
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
39 Levine MN, Hirsh J. Hemorrhagic complications of anticoagulant therapy. Semin Thromb Haemost 1986; 12: 39-57
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
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
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
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
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
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
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
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
48 Ellison N, Edmunds LH, Colman RW. Platelet aggregation following heparin and protamine administration. Anesthesiology 1994; 48: 65-68
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
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
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
52 Hirsh J, Heparin N, Engl J Med. 1991; 324 (22) 1565-1574
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
54 Fedderick WCampbell. The contribution of platelet dysfunction to postbypass bleeding. J Cardiothorac Vase Anesth 1991; 05 (06) (Suppl. 01) 08-12