Ann Thorac Surg 2006;81:624
© 2006 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Henry M. Rinder, MD
Departments of Laboratory Medicine and Internal Medicine (Hematology), Yale School of Medicine, 333 Cedar St, PO Box 208035, New Haven, CT 06520-8035
(Email: henry.rinder{at}yale.edu).
Cardiopulmonary bypass (CPB) reveals the delicate balance between hemostatic and anti-thrombotic physiologies. Physicians have long attempted to develop protocols that block platelet thrombotic tendencies during CPB (ie, so-called "platelet anesthesia"), yet they promote subsequent platelet recovery to preserve hemostasis post-CPB. Aprotinin has been proposed to contribute to these processes by a blockade of protease-activated receptor 1 (PAR1)-dependent platelet activation during CPB and inhibition of post-CPB fibrinolysis, respectively. Recombinant aprotinin variants, which could be substituted for animal-derived aprotinin, would eliminate the theoretical risk of prior disease transmission. This study by Day and colleagues [1] demonstrates that several aprotinin variants are equal or superior to aprotinin at blocking PAR1-dependent platelet aggregation, providing a further rationale for determining if they may better prevent peri-CPB bleeding.
The CPB protocols (including, but not limited to, aprotinin) have been refined during the years in large part to successfully preserve post-CPB hemostasis. However, recent work has suggested that serious, sometimes subtle, post-CPB complications are related to platelet-dependent thrombosis. A recent study by the MCSPI group demonstrated that early post-CPB reinstitution of aspirin conferred a significant risk reduction in complications related to cerebral, cardiac, and renal systems [2]. The effects of enhanced preservation of the PAR1 receptor on this aspirin-sensitive, post-CPB platelet hypercoagulability cannot be known with any certainty, and this requires further investigation. The dual nature of the effects of aprotinin (ie, antifibrinolytic and inhibiting the PAR1 receptor) are sufficiently complex in the post-CPB patient, so that large patient numbers will need to be studied in a directed manner to define this risk-benefit ratio.
 |
References
|
|---|
- Day JRS, Haskard DO, Taylor KM, Landis RC. Effect of aprotinin and recombinant variants on platelet protease-activated receptor 1 activation Ann Thorac Surg 2006;81:619-624.[Abstract/Free Full Text]
- Mangano DT. Aspirin and mortality from coronary bypass surgery New Engl J Med 2002;347:1309-1317.[Abstract/Free Full Text]
Top
References