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A single dose of aprotinin prevents platelet hyporeactivity after coronary artery bypass graft surgery
Wojciech Szczeklik1, Włodzimierz Morawski, Marek Sanak
12nd Department of Medicine, Jagiellonian University Medical Collage, Kraków, Poland. wszczeklik@gmail.com
Insights
Aprotinin reduces bleeding after coronary artery bypass graft surgery by improving platelet function, specifically preventing reduced sensitivity to adenosine diphosphate (ADP). This study clarifies aprotinin
Area of Science:
- Cardiovascular Surgery
- Pharmacology
- Hematology
Background:
- Bleeding post-coronary artery bypass graft (CABG) surgery significantly increases mortality.
- Aprotinin use is limited due to cardiovascular complications, despite its efficacy in reducing bleeding.
- The precise mechanism of aprotinin's action on platelet function remains unclear.
Purpose of the Study:
- To investigate the effect of aprotinin on platelet function in patients undergoing CABG surgery.
Main Methods:
- A randomized, placebo-controlled, double-blind study involving 24 CABG patients.
- Assessed platelet activation markers (P-selectin, activated glycoprotein IIb/IIIa) before and after surgery.
- Measured platelet reactivity to adenosine diphosphate (ADP) and thrombin receptor activator for peptide 6 (TRAP-6) in vitro.
- Determined perioperative bleeding and urinary thromboxane A2 metabolites.
Main Results:
- Aprotinin reduced perioperative bleeding by 26% (P <0.01).
- Aprotinin prevented a decrease in platelet sensitivity to ADP post-CABG.
- Platelet reactivity to TRAP-6, platelet count, and thromboxane A2 metabolite excretion were unaffected.
Conclusions:
- Aprotinin may reduce CABG-related bleeding by interfering with the ADP pathway of platelet activation.
- This interference prevents postoperative hyporeactivity of platelets to ADP.
- Aprotinin's effect on platelet reactivity via the PAR-1 receptor was not observed.
Introduction:
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.
Objectives:
The aim of the study was to assess the effect of aprotinin on platelet function in patients undergoing CABG.
Patients And 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.
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