A single dose of aprotinin prevents platelet hyporeactivity after coronary artery bypass graft surgery.
BACKGROUND
Bleeding after coronary artery bypass graft (CABG) surgery is associated with a significant increase in mortality. Even though aprotinin significantly reduces bleeding in patients undergoing cardiac surgery, its use has been recently substantially limited because of serious cardiovascular complications. The exact mechanism of its action, particularly its effect on platelet function, remains unclear.


OBJECTIVE
The aim of the study was to assess the effect of aprotinin on platelet function in patients undergoing CABG.


METHODS
In a randomized placebo-controlled double-blind study, we investigated the effect of a single dose of aprotinin on platelet function in 24 patients who underwent CABG between 2005 and 2006. Before surgery and in the postoperative period, we measured platelet activation markers (P-selectin and activated form of glycoprotein IIb/IIIa) at baseline and following in vitro platelet activation with adenosine diphosphate (ADP) or protease-activated receptor 1 (PAR-1) agonist--thrombin receptor activator for peptide 6 (TRAP-6). Perioperative bleeding and urinary metabolites of thromboxane A2 were also determined.


RESULTS
Aprotinin reduced perioperative bleeding by 26% (P <0.01) and prevented a decrease in platelet sensitivity to ADP immediately after CABG. In vitro platelet reactivity to TRAP-6 remained unchanged. Aprotinin did not affect blood platelet count or urinary thromboxane A2 metabolite excretion after CABG.


CONCLUSIONS
Our results indicate that aprotinin may reduce perioperative bleeding by its interference with ADP pathway of platelet activation, thereby preventing postoperative hyporeactivity of platelets to ADP. Platelet reactivity to PAR-1 receptor agonist was not affected by aprotinin.
Szczeklik
Wojciech
W
2nd Department of Medicine, Jagiellonian University Medical Collage, Kraków, Poland. wszczeklik@gmail.com
Morawski
Włodzimierz
W
Sanak
Marek
M
Jakieła
Bogdan
B
Bolkowski
Maciej
M
Cisowski
Marek
M
Szczeklik
Michał
M
Bochenek
Andrzej
A
Musiał
Jacek
J
D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001792:Blood Platelets / Q000187:drug effects*; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000032:analysis; D016896:Treatment Outcome
D006490:Hemostatics; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D011516:Prothrombin; D007611:Aprotinin; D013917:Thrombin