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J Thorac Cardiovasc Surg 1995;109:402
© 1995 Mosby, Inc.

LETTERS TO THE EDITOR

Invited letter concerning: Topical aprotinin

N. Tabuchi, MD, W. van Oeveren, PhD

Thoraxcenter
Blood Interaction Research
University Hospital
Oostersingel 59
9713 EZ Groningen, The Netherlands

Reply to the Editor:

We thank Dr. Edmunds for his comments on our data and insights. We totally agree with his opinion that the systemic aprotinin remains a proven method to preserve hemostasis and that subsequent studies of topical aprotinin are needed to confirm the efficacy and reveal the mechanism of preserving hemostasis during and after cardiopulmonary bypass (CPB).

When comparing advantages of two protocols of systemic aprotinin (high-dose and low-dose), however, we are faced with two specific questions: Is the inhibition of kallikrein activity needed during CPB to preserve hemostasis? Is the fibrinolysis inhibition in the systemic blood needed after the end of CPB? The kallikrein activity, which is significantly inhibited by the high-dose protocol and not by the low-dose protocol, could accelerate the intrinsic clotting system as pointed out by Dr Edmunds, consequently activating and damaging platelets by thrombin generation Go 1 during CPB. Although some reports Go 2 indicated that high-dose aprotinin significantly reduced clotting activity during CPB, a recent study Go 3 showed that the predominant clotting activity is generated through the extrinsic pathway, which is in accordance with our observation in the pericardial cavity.Go 4 Thus activation of the kallikrein system is probably of minor importance for thrombin generation during CPB. These conflicting results make the clinical relevance of kallikrein inhibition on preserving hemostasis questionable. The second conflicting point is the importance of fibrinolysis inhibition in the systemic blood after CPB on preserving hemostasis, which could be achieved only by the high-dose protocol. Our previous study Go 5 demonstrated that fibrinolysis stimulating activity is locally intensified inside the thoracic cavity after operation, which is quite in contrast to the rapidly disappearing activity in the systemic blood after CPB. These data suggest that hemostatic fibrin sealing on the wound surface could be attacked by fibrinolysis more from the side of the wound surface than of systemic blood after CPB. According to this speculation, the topical use of aprotinin on the surgical wound at the end of operation makes sense, and the importance of maintaining systemic high concentrations of aprotinin after CPB has been challenged.

As stated by Dr Edmunds, nothing is ever simple in the hemostatic mechanism of patients after CPB. Every finding will give us a clue to reveal the mechanism of hemostasis and improve therapy.

References

  1. Coughlin SR, Vu TH, Hung DT, Wheaton VI. Characterization of a functional thrombin receptor. J Clin Invest 1992;89:351-5.
  2. Spannagl M. Dietrich W, Beck A, Schramm W. High dose aprotinin reduces prothrombin and fibrinogen conversion in patients undergoing extracorporeal circulation for myocardial revascularization. Thromb Haemost 1994;72:159-65.
  3. Boisclair MD, Lane DA, Philippou H, et al. Mechanism of thrombin generation during surgery and cardiopulmonary bypass. Blood 1993;82:3350-7.
  4. Tabuchi N, de Haan J, Boonstra PW, van Oeveren W. Activation of fibrinolysis in the pericardial cavity during cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1993;106:828-33.
  5. de Haan J, Schonberger JPAM, Haan J, van Oeveren W, Eijgelaar A. Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during reperfusion of shed blood after cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1993;106:1017-23.




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