Thromb Haemost 1995; 74(05): 1293-1297
DOI: 10.1055/s-0038-1649929
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

Individual Variations in the Fibrinolytic Response During and After Cardiopulmonary Bypass

W L Chandler
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
,
J C K Fitch
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
,
M H Wall
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
,
E D Verrier
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
,
R P Cochran
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
,
L O Soltow
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
,
B D Spiess
The Departments of Laboratory Medicine, Anesthesiology and the Cardiovascular Surgery Division of the Department of Surgery at the University of Washington, Seattle, Washington, USA
› Author Affiliations
Further Information

Publication History

Received 21 March 1995

Accepted after resubmission 08 August 1995

Publication Date:
10 July 2018 (online)

Summary

The purpose of this study was to determine whether individual patients show different patterns of fibrinolytic response to cardiopulmonary bypass (CPB) and whether preoperative or intraoperative parameters were predictive of these different patterns. Active t-PA, active PAI-1 and total t-PA antigen were measured in plasma samples obtained from 38 subjects, age 32 to 85 (median 69 years), before, during and after CPB. Four patterns of fibrinolytic response were noted: 1) 40% of patients showed the “typical” response, a rapid rise in active and total t-PA during CPB followed postoperatively by elevated PAI-I and reduced t-PA, 2) 10% showed no change in t-PA or PAI-1 during or after CPB, 3) 24% showed no change in t-PA with an increase in PAI-1 postoperatively, and 4) 26% showed an increase in t-PA during CPB with no change in PAI-1 postoperatively. When present, the t-PA response was rapid, occurring within the first 30 min of CPB and was more common in patients undergoing valve surgery than in coronary artery bypass grafting (p <0.005). Increased levels of PAI-1 postoperatively were associated with ischemic times greater than 70 min (p = 0.003) but not with the total length of CPB. Age, sex, CPB temperature, total CPB time and preoperative levels of t-PA and PAI-1 were not associated in the intra- or postoperative fibrinolytic response pattern. We conclude that the fibrinolytic response to CPB is heterogeneous. Further studies will be needed to determine whether different response patterns are clinically significant.

 
  • References

  • 1 Stibbe J, Kluft C, Brommer E, Gomes M, Jong D de, 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
  • 2 Royston D, Bidstrup B, Taylor K, Sapsford R. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 1987; 2: 1289-1291
  • 3 van Oeveren W, Jansen N, Bidstrup B, Royston D, Westaby S, Neuhof H, Wildevuur C. Effeets of aprolinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thome Surg 1987; 44: 640-645
  • 4 Wildlevuur C, Eijsman L, Roozendaal K, Harder M, Chang M, van Oeveren W. Platelet preservation during cardiopulmonary bypass with aprolinin. Lur J Cardiothorac Surg 1989; 3: 533-537
  • 5 Marx G, Pokar H, Reuter H, Doering V, Tilsner V. The effects of aprolinin on hemostatic function during cardiac surgery. J Cardiothor Vase Anesth 1991; 5: 467-474
  • 6 Horrow JC, Hlavacck J, Strong MD, Collier W, Brodsky I, Goldman SM, Goel IP. Prophylactic tranexamic acid decreases bleeding after cardiac operations. J Thoraca Cardiovasc Surg 1990; 99: 70-74
  • 7 Prins MH, Hirsh J. A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism. Arch Intern Med 1991; 151: 1721-1731
  • 8 Gram J, Janetzko T, Jespersen J, Bruhn H. Enhanccd effective fibrinolysis following the neutralization of heparin in open heart surgery increases the risk of postsurgical bleeding. Thromb Haemost 1990; 63: 241-245
  • 9 Paramo J, Rifon J, Llorcns R, Casarcs J, Paloma M, Rocha E. Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery. Haemost 1991; 21: 58-64
  • 10 Hamsten A, Walldius G, Szamosi A, Blombäck M, De Faire U, Dahlen G, Landou C, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3-9
  • 11 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-1168
  • 12 Munkvad S, Gram J, Jespersen J. A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction. European Heart Journal 1990; 11: 525-528
  • 13 Jansson JH, Olofsson BO, Nilsson TK. Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease. Circulation 1993; 88: 2030-2034
  • 14 Gram J, Jespersen JA. selective depression of tissue plasminogen activator (t-PA) activity in euglobulin characterizes a risk group among survivors of acute myocardial infarction. Thromb Haemost 1987; 61: 289-293
  • 15 Zalewski A, Shi Y, Nardone D, Bravette B, Weinstock P, Fischman D, Wilson P, Goldberg S, Levin DC, Bjornsson TD. Evidence for reduced fibrinolytic activity in unstable angina at rest. Clinical, biochemical, and angiographic correlates Circulation 1991; 83: 1685-1691
  • 16 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati MB, Cardillo M, Catalano M, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, Pozzoli E, Turri M, Group P. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. Arterioscler Thromb 1993; 13: 1412-1417
  • 17 Margaglione M, Di Minno G, Grandone F, Vecchione G, Celentano E, Cappucci G, Grilli M, Simone P, Panico S, Mancini M. Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor 1 in patients with a history of ischemic stroke. Arterioseler Thromb 1994; 14: 1741-1745
  • 18 Rosenfeld BA, Beattie C, Christopherson MD, Norris EJ, Frank SM, Breslow MJ, Rock P, Parker SD, Gottlieb SO, Perler BA, Williams GM, Siedler A, Bell W. The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Anesthesiology 1993; 79: 435-443
  • 19 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
  • 20 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 Haemost 1989; 62: 917-922
  • 21 Chandler WL, Trimble SL, Loo SC, Mornin D. Effect of PAL 1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-l complex in plasma. Blood 1990; 76: 930-937
  • 22 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
  • 23 Amiral J, Plassart V, Grosley M, Mimilla F, Constant G, Guyader AM. Measurement of tPA - PAI-1 complexes by ELISA, using monoclonal antibodies: clinical relevance. Thromb Res 1988; Suppl (Suppl. 08) 99-113
  • 24 Declerck PJ, Verstreken M, Collen D. An immunolunctional assay for active plasminogen activator inhibitor-1 (PALI). Fibrinolysis 1988; 2 Suppl (Suppl. 02) 17-18
  • 25 Alessi MC, Juhan-Vague I, Declerck PJ, Anfosso F, Gueunoun E, Collen D. Correlations between t-PA and PAI-1 antigen activity and t-PA/PAI-l complexes in plasma of control subjects and of patients with increased t-PA or PAI-1 levels. Thromb Res 1990; 60: 509-516
  • 26 Teufelsbauer H, Proidl S, Havel M, Vukovich T. Early activation of hemostasis during cardiopulmonary bypass: evidence of thrombin mediated hyperfibrinolysis. Thromb Haemost 1992; 68: 250-252
  • 27 Burman J, Chung H, Lane D, Philippou H, Adami A, Lincoln J. Role of factor XII in thrombin generation and fibrinolysis during cardiopulmonary bypass. Lancet 1994; 344: 1192-1193
  • 28 Kluft C, Verheijen J, Jie A, Rijken D, Presto F, Sue-Ling H, Jespersen J, Aasen A. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985; 45: 605-610
  • 29 Mangano D, Siliciano D, Hollenberg M, Leung J, Browner W, Goehner P, Merrick S, Verrier E, Group SR. Postoperative myocardial ischemia. Anesthesiology 1992; 76: 342-353