Abstract 3045: Aprotinin’s Role as an Inhibitor of Prothombotic Agents in Off-Pump Coronary Artery Bypass
Objective: Aprotinin is known for its hemostatic effect during coronary artery bypass grafting (CABG). While hemostasis appears to be mediated via a variety of mechanisms, aprotinin blocks platelet activation via the thrombin receptor, PAR-1, which would suggest the potential to have an antithrombotic effect. The purpose of this study was to investigate the clinical impact of PAR-1 antagonism by aprotinin.
Methods: A series of hematologic assays were performed using ELISA or flow cytometry on patients undergoing off-pump CABG randomized into 2 groups:
those receiving saline infusion during CABG (n=30) and
those receiving aprotinin (2x106 KIU loading dose, followed by 0.5x106 KIU/h [n=30]).
After grafting, arterial (A) and coronary sinus (CS) blood samples were obtained to calculate the CS-A gradient of F1.2 (marker of thrombin formation), factor XIIa (contact activation), conjugated platelets and platelet-derived microparticles (platelet activation). Optical coherence tomography (OCT) was used to image bypass conduits after harvest and CT angiography was used to determine predischarge graft patency.
Results: In placebo patients, high levels of F1.2, FXIIa, and activated platelets were noted in CS blood and OCT imaging revealed clot on average within 39% of the length of the harvested vein conduits. All of these prothrombotic endpoints were reduced by aprotinin treatment (Table⇓). CT angiography revealed a total of 4 graft occlusions, 3 in the placebo group (p=NS).
Conclusion: As a broad spectrum serine protease inhibitor, aprotinin has a variety of effects when used during CABG. This study demonstrates that PAR1 mediated effects of thrombin can be inhibited by aprotinin. In addition, the reduction in the size of clot strands that are typically retained during endoscopic saphenous vein harvest may represent an antithrombotic clinical effect of aprotinin. Ongoing studies will address whether these actions influence early graft patency after OPCAB.