Heparin Therapy during Cardiopulmonary Bypass in Children Requires Ongoing Quality Control

Maureen Andrew; Brian MacIntyre; James MacMillan; William G Williams; Colleen Gruenwald; Marilyn Johnston; Fred Burrows; Elaine Wang; Margaret Adams

doi:10.1055/s-0038-1649703

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1993; 70(06): 0937-0941
DOI: 10.1055/s-0038-1649703

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

Heparin Therapy during Cardiopulmonary Bypass in Children Requires Ongoing Quality Control

Maureen Andrew

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

Brian MacIntyre

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

James MacMillan

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

William G Williams

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

Colleen Gruenwald

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

Marilyn Johnston

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

Fred Burrows

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

Elaine Wang

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

,

Margaret Adams

The Department Pediatrics and Pathology, McMaster University, Hamilton, Ontario and The Hospital for Sick Children, Toronto, Ontario, Canada

› Institutsangaben

Abstract

als PDF herunterladen

Summary

Heparin therapy for children undergoing cardiopulmonary bypass (CPB) is monitored in the operating room by automated whole blood activated clotting times (ACT). For many years our institution used Hemochron (HC) ACT machines but changed to HemoTec (HT) ACT machines because they required a smaller blood sample and provided results in duplicate. When HemoTec ACT machines were introduced at our institution, the surgical team was concerned that increased amounts of heparin were being administered to our patients during CPB. This study was conducted to investigate the potential mechanisms responsible for these clinical observations. First, we compared ACT values on ex vivo blood samples from 20 consecutive pediatric patients (6 samples each) during CPB. The HC ACT values were significantly and systematically increased over HT ACT values (HC: 750 ± 40 vs HT: 418 ± 26, Mean ± SEM, p <0.01). 94% of all HC ACT values were above 450 s compared to only 27% of HT ACT values. If HT ACT values had been used for patient monitoring, all patients would have received more heparin to achieve ACT values above 450 s. The two machines reported similar ACT values when heparin was added in vitro to whole blood (0.1-5.0 units/ml), (HC: Y = 98X + 104, r² = 0.93 HT: Y = 82X + 109, r² = 0.94). Heparin concentrations in our patients following a bolus of 300 U/kg of heparin, but prior to CPB were 3.2 ± 0.07 units/ml. Following the initiation of CPB, heparin concentrations decreased to 1.3 ± 0.05, reflecting, in part, hemodilution by the pump prime (1 U of heparin/ml). In contrast to the in vitro results, there was no relationship between ACT values measured by either machine and plasma heparin concentrations in ex vivo samples. Finally, plasma concentrations of 8 coagulation proteins measured prior to CPB and following CPB were decreased by 27-55%, predominantly reflecting the final dilution by CPB. In conclusion: 1) HT and HC machines cannot be used interchangeably in pediatric patients without risk of altering clinical practice in an uncontrolled fashion; and 2) ACT values from children on CPB correlate poorly with heparin concentrations, likely due to hemodilution. Optimal use of anticoagulant therapy during CPB in children requires further study in clinical trials and ongoing quality control.

PDF (1062 kb)

Referenzen

References
1 Hattersley P. Activated coagulation time of whole blood. JAMA 1966; 196 (05) 150-154
2 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
3 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
4 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
5 Keeth J, Trickey T, King E, Stafford T, Mclnnis R, Reed C. A clinical evaluation of the hemoTec ACT. Proc Am Acad Cardio Perf 1988; 9: 22-25
6 Refn I, Vestergaard L. The titration of heparin with protamine. Scand J Clin Lab Invest 1954; 6: 284-287
7 Zipursky A, Johnston M, de Sa D, Hsu E, Milner R. Clinical and laboratory diagnosis of hemostatic disorders in newborn infants. Am J Pediatr Hematol/Oncol 1979; 1: 217-226
8 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation system in the fullterm infant. Blood 1987; 70 (01) 165-172
9 Kisker C. Detection of fibrin monomer. J Clin Pathol 1979; 72: 405
10 Snedecor GW, Cochran WG. Regression, 9.14: Regression when X is subject to error. Ames, Iowa: Iowa State University Press; 1980: 171-172
11 Levine MN, Hirsh J. Hemorrhagic complications of anticoagulant therapy. Semin Thrombos Haemostas 1986; 12: 39-57
12 Jumean HG, Sudah F. Monitoring of anticoagulant therapy during open-heart surgery in children with congenital heart disease. Acta Haematol 1983; 70: 392-395
13 von Segesser L, 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 Cardio-thorac Surg 1990; 4: 639-643
14 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
15 Horkay F, Martin P, Saeed W, Rajah SM, Walker DR. Measurement of the activated clotting time (ACT) during cardiopulmonary bypass in children: Is it relevant?. J Cardiovasc Surg 1991; 32: 80
16 Reich DL, Zahl K, Perucho MH, Thys DM. An evaluation of two activated clotting time monitors during cardiac surgery. J Clin Monitor 1992; 8 (01) 33-36
17 Green TP, Ischam-Schopf B, Steinhorn RH, Smith C, Irmiter RJ. Whole blood activated clotting time in infants during extracorporeal membrane oxygenation. Crit Care Med 1990; 18: 494-498
18 Butt RW, Leblanc P, Dermody L. Correlation of plasma heparin levels with automated clotting times during cardiopulmonary bypass. Can J Med Tech 1980; 42: 83-84
19 Gravlee GP, Case LD, Angert KC, Rogers AT, Miller GS. Variability of the activated coagulation time. Anesth Anal 1988; 67: 469-472
20 Stenbjerg S, Berg E, Albrechtsen OK. Heparin levels and activated clotting time (ACT) during open heart surgery. Scand J Haematol 1981; 26: 281-284
21 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
22 Stenbjerg S, Berg E, Albrechtsen OK. Evaluation of the activated whole blood clotting time (ACT) in vitro. Scand J Haematol 1979; 23: 239-244
23 Giuliani R, Szwarcer E, Aquino EM, Palumbo G. Fibrin-dependent fibrinolytic activity during extracorporeal circulation. Thromb Res 1991; 61: 369-373
24 Hirsh J. Oral anticoagulant drugs. Review article. N Engl J Med 1991; 324: 1865-1875
25 Hirsh J, Poller L, Deykin D, Levine M, Dalen JE. Optimal therapeutic range for oral anticoagulants. Chest 1989; 95 (02) 05S-11S
26 Poller L. Progress in standardization anticoagulation control. Hematology Review 1987; 1: 225-241
27 Shojania AM, Tetreault J, Turnbull G. The variations between heparin sensitivity of different lots of activated partial thromboplastin time reagent produced by the same manufacturer. Am J Clin Pathol 1988; 89: 19-23
28 Hirsh J. Heparin. N Engl J Med 1991; 324 (22) 1565-1574