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DOI: 10.1055/s-0038-1645202
Enhanced Effective Fibrinolysis following the Neutralization of Heparin in Open Heart Surgery Increases the Risk of Post-Surgical Bleeding
Publication History
Received 26 June 1989
Accepted after revision 23 November 1989
Publication Date:
02 July 2018 (online)
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Summary
The tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracor-poreal circulation (p <0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p <0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p <0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p <0.05).
We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery
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References
- 1 Bick RL. Hemostasis defects associated with cardiac surgery, prothetic devices, and other extracorporeal circuits. Semin Thromb Hemostas 1985; 11: 249-280
- 1 Edmunds LH, Addonizio VR. Extracorporeal circulation. In: Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) JB Lippincott Company, Philadelphia: 1987: 901-912
- 3 Stratta P, Canavese C, Costa P. et al Biological stress induced by extracorporeal circulation: comparison between cardiopulmonary bypass, hemodialysis and plasma exchange. Trans Am Soc Artif Intern Organs 1984; 30: 502-507
- 4 Kucuk O, Kwaan HC, Frederickson J, Wade L, Green D. Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation. Am J Hematol 1986; 23: 223-229
- 5 Kluft C. Occurrence of C1-inactivator and other proteinase inhibitors in euglobulin fractions and their influence on fibrinolytic activity. Haemostasis 1976 5. 136-146
- 6 Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
- 7 Stibbe J, Kluft C, Brommer EJ P, Gomes M, De Jong DS, Nauta J. Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest 1984; 14: 375-382
- 8 Mammen EF, Koets MH, Wasington BC. et al Hemostasis changes during cardiopulmonary bypass surgery. Semin Thromb Hemostas 1985; 11: 281-292
- 9 Bagge L, Lilienberg G, Nyström S-O, Tydén H. Coagulation, fibrinolysis and bleeding after open-heart surgery. Scand J Thorac Cardiovasc Surg 1986; 20: 151-160
- 10 Holloway DS, Summaria L, Sandesara J, Vagher JP, Alexander JC, Caprini JA. Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients. Thromb Haemostas 1988; 59: 62-67
- 11 Jespersen J, Knudsen LH, Sidelmann J. The use of evacuated glass tubes for collection of blood samples for fibrinolytic assays. Thromb Res 1982; 25: 173-176
- 12 Verheijen JH, Mullaart E, Chang GT G, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-269
- 13 Jespersen J, Sidelmann J. Individual levels of plasma α2-antiplasmin and α2-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen. Thromb Haemostas 1983; 50: 581-585
- 14 Gram J, Jespersen J. A functional plasminogen assay utilizing the potentiating effect of fibrinogen to correct for the overestimation of plasminogen in pathological plasma samples. Thromb Haemostas 1985; 53: 255-259
- 15 Gram J, Jespersen J. A simplified estimation of tissue plasminogen activator (t-PA) inhibition in human plasma. Fibrinolysis 1987; 1: 33-37
- 16 Rijken DC, Sprengers ED, van der Hoeven RJ, Kluft C, Engesser L. Plasminogen activator inhibitor 1 (PAI-1) antigen levels in human plasma. Fibrinolysis 1988; (Suppl. 02) 2: 79-82
- 17 Stötzer K-E, Amiral J, Spanuth E. Neue Methoden zur spezifischen Bestimmung von Fibrinspaltprodukten (D-Dimere). Lab Med 1988; 12: 51-59
- 18 Koppert PW, Kuipers W, Hoegee de-Nobel B, Brommer EJ P, Koopmann J, Nieuwenhuizen W. A quantitative enzyme immunoassay for primary fibrinogenolysis products in plasma. Thromb Haemostas 1987; 57: 25-28
- 19 Astrup T. Tissue activators of plasminogen. Fed Proc 1966; 25: 42-51
- 20 Rånby M. Studies on the kinetics of plasminogen activator. Biochim Biophys Acta 1982; 704: 461-469
- 21 Brommer EJ P. The level of extrinsic plasminogen activator (t-PA) during clotting as a determinant of the rate of fibrinolysis; inefficiency of activators added afterwards. Thromb Res 1984; 34: 109-114
- 22 Royston D, Bidstrup BP, Taylor KM, Sapsford RN. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 1987; 2: 1289-12891
- 23 Köstering H, Kirchhof PG, Völker P, Warmann E, Koncz J. Untersuchungen der Blutgerinnungsveranderungen wahrend und nach Operation mit Hilfe der Herz-Lungen-Maschine. Thoraxchir-urgie 1973; 21: 534-543