The clinical benefit of
aprotinin with respect to improved hemostasis, platelet function, and inflammatory response to
cardiopulmonary bypass (CPB) surgery has been well documented, but these benefits have been overshadowed by the concern that such a potently
hemostatic agent might also be prothrombotic. In this article, we discuss recent advances in the understanding of the basic mechanism of
aprotinin that have led to the identification of new antiinflammatory targets and the discovery that
aprotinin is, in fact, antithrombotic with respect to platelets. Its antithrombotic action is mediated by the selective blocking of the major
thrombin receptor, the
protease-activated receptor 1 (PAR1), but not other receptors of platelet activation (ie,
collagen,
adenosine diphosphate [
ADP], or
epinephrine receptors). The selective targeting of PAR1 enables
aprotinin to protect platelets from unwanted activation by
thrombin generated during CPB surgery (consistent with a role in platelet-preservation), while permitting the participation of platelets in the formation of
hemostatic plugs at
wound and
suture sites, where
collagen,
ADP, and
epinephrine are most likely to be expressed.
Aprotinin therefore exerts a subtle
hemostatic yet antithrombotic mechanism of action, which, when allied with its multitiered antiinflammatory effect, makes this
drug a valuable companion to cardiac surgery.