Characterization of platelet aggregation responses in microminipigs: Comparison with miniature pigs and the influence of dual antiplatelet administration of aspirin plus prasugrel

- Prasugrel plus aspirin inhibited ADP- and collagen-induced platelet aggregation in microminipigs.
- Prasugrel plus aspirin also inhibited both platelet aggregations in Clawn miniature pigs.
- There were no obvious differences in platelet responses to DAPT between both pigs.
- Microminipigs are useful experimental animals for platelet and thrombosis research.

We aimed to characterize platelet aggregation responses and the impact of dual antiplatelet therapy in microminipigs. In this in vitro study, both adenosine-5′-diphosphate (ADP, 5-50 μM) and collagen (2-20 μg/ml) induced concentration-related platelet aggregation in the microminipigs; 20 μM ADP and 5 and 12.5 μg/ml collagen were selected for further ex vivo studies. Aspirin plus prasugrel were administered orally for 7 days (n = 4/each group). Ex vivo platelet aggregation was analyzed on Day 1 (1 and 4 h after administration), Day 4 (4 h), and Day 7 (4 h) under three different prasugrel dosing regimens: LD0/MD1 (1 mg/kg/day), LD0/MD3 (3 mg/kg/day), and LD10/MD1 (10 mg/kg loading dose and 1 mg/kg/day maintenance dose). Aspirin (10 mg/kg/day) was administered to all groups. In the presence of aspirin, prasugrel at 3 and 10 mg/kg significantly inhibited ADP-induced platelet aggregation on Day 1. On Days 4 and 7, significant inhibition of platelet aggregation (IPA) was also observed in each group. With 5 μg/ml collagen-induced platelet aggregation, all three groups showed significant IPA at 4 h on Day 1 or later. In 12.5 μg/ml collagen-induced platelet aggregation, all groups showed significant effects on Days 4 and 7; however, the 30%-35% IPA was considerably lower than that (50%-60%) found with 5 μg/ml collagen. In Clawn miniature pigs, similar inhibitory patterns were observed for both ADP- and collagen-induced ex vivo platelet aggregation. In conclusion, these results indicated that microminipigs as well as miniature pigs may represent useful experimental animals for thrombosis research.