Ann Thorac Surg 2002;74:393
© 2002 The Society of Thoracic Surgeons
Invited commentary
John Pepper, MChir.FRCSa
a Department of Surgery, Royal Brompton Hospital, Sydney St, London SW3 6NP, England UK
e-mail: j.pepper{at}rbh.nthames.nhs.uk
Tranexamic acid and aprotinin are routinely used to reduce bleeding in cardiac surgery. Aprotinin is a serine protease inhibitor of low molecular weight, isolated from bovine lung. In a high dose formulation, the Hammersmith group showed that it was effective in reducing the need for blood transfusion in adults undergoing redo surgery or surgery for infective endocarditis and in primary coronary surgery. But it was not long before surgeons ran into problems with control of the clotting time in some patients receiving aprotonin. There are two methods commonly used for automatic clotting times. They use different systems for activation of coagulation and monitoring of the time to clot formation. Hemochron (International Techdyne Corporation, Edison, NJ) uses celite as the activator. The Hemo-Tec system (Hemo-Tec Inc, Englewood, CO.) uses kaolin as the activator. There are significant differences between results when these instruments are used on the same blood sample drawn during open heart surgery and when aprotinin is administered to the heparinised patient on cardiopulmonary bypass. This is due to the effect of the activator. Kaolin is a very powerful activator of the intrinsic coagulation system and therefore aprotinin has little effect on activation in its presence whereas clotting induced by contact with other surfaces is inhibited by aprotinin.
Tranexamic acid is a potent inhibitor of fibrinolysis. Unlike aprotinin, it is not antigenic and it is considerably cheaper. It acts by competitive blocking of lysine binding sites on plasminogen. It has a greater efficacy, longer half-life and stronger plasminogen-binding capacity than epsilon-amino-caproic acid. Patients receiving tranexamic acid demonstrate fewer fibrin degradation products and a marked decrease in plasminogen availability. In view of its mechanism of action we would not expect the nature of the activator in the automatic clotting instrument to have any influence on the result. But as the authors imply, the action of drugs is rarely pure and tranexamic acid is a relative newcomer to the setting of cardiopulmonary bypass. It is therefore reassuring to have this report from Bechtel and colleagues on patients undergoing primary cardiac surgery. Larger studies on higher risk patients including reoperations are needed. As with all anti-fibrinolytic treatment, there remains a small risk with Tranexamic acid of microvessel thrombosis particularly in septic patients. For the present therefore, aprotinin is probably a wiser choice for patients undergoing cardiac surgery in the presence of severe infection.1
References
- Bidstrup B.P., Royston D., Sapsford R.N., Taylor K.M. Reduction in blood loss and blood use after cardiopulmonary bypass with high dose aprotinin. J Thorac Cardiovasc Surg 1989;97:364-372.[Abstract]
