PDF herunterladen
Thromb Haemost 1997; 78(02): 820-826
DOI: 10.1055/s-0038-1657635
Rapid Communication
Schattauer GmbH Stuttgart

A Comparison of Thromboelastography with Heparinase or Protamine Sulfate Added In Vitro during Heparinized Cardiopulmonary Bypass

Bruce D Spiess
1   The University of Washington, Department of Anesthesiology, Yale University, New Haven, CT, USA
,
Michael H Wall
2   The University of Washington, Dept of Anesthesiology, Lacklond AFB, TX, Yale University, New Haven, CT, USA
,
Bruce S Gillies
1   The University of Washington, Department of Anesthesiology, Yale University, New Haven, CT, USA
,
Jane C K Fitch
3   The University of Washington, Dept of Anesthesiology, Yale University, New Haven, CT, USA
,
Louise O Soltow
1   The University of Washington, Department of Anesthesiology, Yale University, New Haven, CT, USA
,
Wayne L Chandler
4   The University of Washington, Department of Laboratory Medicine, Yale University, New Haven, CT, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 19. 1996

Accepted after resubmission 03. April 1997

Publikationsdatum:
12. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Thromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.

 

  • References

  • 1 Mammen EF, Koets MH, Washington BC, Wolk LW, Brown JM, Burdick M, Selik NR, Wilson RF. Hemostasis changes during cardiopulmonary bypass. Semin Thromb Hemost 1985; 11: 281-292
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 2 Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault K, Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991; 75: 388-393
    CrossrefPubMedGoogle Scholar
  • 3 Boldt J, Zickmann B, Czeke A, Herold C, Dapper F, Hempelmann G. Blood conservation techniques and platelet function in cardiac surgery. Anesthesiology 1991; 75: 426-432
    CrossrefPubMedGoogle Scholar
  • 4 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
  • 5 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. J Cardiothorac Anesth 1989; 3: 181-188
    CrossrefPubMedGoogle Scholar
  • 6 Freyburger G, Janvier G, Dief S, Boisseau MR. Fibrinolytic and hemorrheologic alterations during and after elective aortic graft surgery: Implications for postoperative management. Anesth Analg 1993; 76: 504-512
    PubMedGoogle Scholar
  • 7 Chandler WL, Fitch JCK, Wall MH, Verrier ED, Cochran RP, Soltow LO, Spiess BD. Individual variations in the fibrinolytic response during and after cardiopulmonary bypass. Thromb Haemost 1995; 74: 1293-1297
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 8 Marengo-Rowe AJ, Leveson JE. Fibrinolysis: A frequent cause of bleeding. In: Ellison N, Jobes DR. eds. Effective Hemostasis in Cardiac Surgery. Philadelphia: WB Saunders; 1988: 43
    Google Scholar
  • 9 Metz S, Keats AS. Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding. Ann Thorac Surg 1990; 49: 440-444
    CrossrefPubMedGoogle Scholar
  • 10 Chandler WL. The thromboelastograph and the thromboelastograph technique. Sem Thromb Hemostas 1996; 21 (Suppl. 04) 1-6
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 11 Spiess BD, Tuman KJ, McCarthy RJ, DeLaria GA, Schillo R, Ivankovich AD. Thromboelastography as an indicator of post-cardiopulmonary bypass coagulopathies. J Clin Monit 1987; 3: 25-30
    CrossrefPubMedGoogle Scholar
  • 12 Martin P, Horkay F, Rajah SM, Walker DR. Monitoring of coagulation status using thromboelastography during paediatric open heart surgery. Int J Clin Monit Comput 1991; 8: 183-187
    CrossrefPubMedGoogle Scholar
  • 13 Kang YG, Martin DJ, Marquey J, Lewis JH, Bontempo FA, Shaw Jr BW, Starzl TE, Winter PM. Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation. Anesth Analg 1985; 64: 888-896
    PubMedGoogle Scholar
  • 14 Essell JH, Martin TJ, Salinas J, Thompson JM, Smith VC. Comparison of thromboelastography to bleeding time and standard coagulation tests in patients after cardiopulmonary bypass. J Cardiothorac Vase Anesth 1993; 7: 410-415
    CrossrefPubMedGoogle Scholar
  • 15 Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD. Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass. Anesth Analg 1989; 69: 69-75
    PubMedGoogle Scholar
  • 16 Tuman KJ, McCarthy RJ, Djuric M, Rizzo V, Ivankovich AD. Evaluation of coagulation during cardiopulmonary bypass with a heparinase-modified thromboelastographic assay. J Cardiothorac Vase Anesth 1994; 8: 144-149
    PubMedGoogle Scholar
  • 17 Gouin I, Lecompte T, Morel MC. In vitro effect of plasmin on human platelet function in plasma. Inhibition of aggregation caused by fibrino-genolysis. Circulation 1992; 85: 935-941
    CrossrefPubMedGoogle Scholar
  • 18 Rinder CS, Mathew JP, Rinder HM, Bonan J, Ault KA, Smith BR. Modulation of platelet surface adhesion receptors during cardiopulmonary bypass. Anesthesiology 1991; 75: 563-570
    CrossrefPubMedGoogle Scholar
  • 19 Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA. Thromb Haemost 1985; 54: 684-687
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 20 Shinoda T, Arakura H, Katakura M, Shirota T, Nakagawa S. Usefulness of thromboelastography for dosage monitoring of low molecular weight heparin and unfractionated heparin during hemodialysis. Artif Organs 1990; 14: 413-415
    CrossrefPubMedGoogle Scholar
  • 21 Gram J, Janetzko T, Jespersen J, Bruhn HD. Enhanced effective fibrinolysis following the neutralization of heparin in open heart surgery increases the risk of post-surgical bleeding. Thromb Haemost 1990; 63: 241-245
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 22 Royston D, Bidstrup B, Taylor K, Sapsford R. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 1987; 02: 1289-1291
    PubMedGoogle Scholar
  • 23 Dietrich W, Mossinger H, Spannagl M, Jochum M, Wendt P, Barankay A, Meisner H, Richter JA. Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations. J Thorac Cardiovasc Surg 1993; 105: 712-720
    CrossrefPubMedGoogle Scholar
  • 24 Marx G, Pokar H, Reuter H, Doering V, Tilsner V. The effects of aprotinin on hemostatic function during cardiac surgery. J Cardiothor Vase Anesth 1991; 05: 467-474
    PubMedGoogle Scholar
  • 25 van OeverenW, Jansen N, Bidstrup B, Royston D, Westaby S, Neuhof H, Wildevuur C. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg 1987; 44: 640-645
    CrossrefPubMedGoogle Scholar
  • 26 Wildevuur C, Eijsman L, Roendaal K, Harder M, Chang M, van OeverenW. Platelet preservation during cardiopulmonary bypass with aprotinin. Eur J Cardiothorac Surg 1989; 03: 533-537
    CrossrefPubMedGoogle Scholar
  • 27 Gram J, Janetzko T, Jespersen J, Bruhn HD. Enhanced effective fibrinolysis following the neutralization of heparin in open heart surgery increases the risk of post-surgical bleeding. Thromb Haemostas 1990; 63: 241-245
    PubMedGoogle Scholar
  • 28 Chandler WL, Trimble SL, Loo SC, Momin D. Effect of PAI-1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-1 complex in plasma. Blood 1990; 76: 930-937
    PubMedGoogle Scholar
  • 29 Chandler WL, Levy WC, Stratton JR. The circulatory regulation of t-PA and u-PA secretion, clearance and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation 1995; 92: 2984-2994
    CrossrefPubMedGoogle Scholar
  • 30 Chandler WL, Schmer G, Stratton JR. Optimum conditions for the stabilization and measurement of tissue plasminogen activator activity in human plasma. J Lab Clin Med 1989; 113: 362-371
    PubMedGoogle Scholar
  • 31 Ranby M, Sundell B, Nilsson TK. Blood collection in strong acidic citrate anticoagulant used in a study of dietary influence on basal tPA activity. Thromb Haemostas 1989; 62: 917-922
    PubMedGoogle Scholar
  • 32 Booth NA, Robbie LA, Croll AM, Bennett B. Lysis of platelet-rich thrombi: the role of PAI-1. Ann N Y Acad Sci 1992; 667: 70-80
    CrossrefPubMedGoogle Scholar