Abstract ID 17622

Poster Board 561

Arterial thrombosis remains the most common cause of death in the developed world. Clopidogrel, a P2Y12 antagonist, is often prescribed to inhibit platelet activation and aggregation; however, patients who take clopidogrel are known to have cerebral bleeding events. The purpose of this study was to determine if the clopidogrel bleeding effect is dependent on P2Y12 receptor inhibition. Previous research from our laboratory suggests that clopidogrel possesses inhibitory effects on hemostasis independent of platelet P2Y12 inhibition. We hypothesized that P2Y12-deficient mice treated with clopidogrel will bleed significantly more than the P2Y12-deficient mice treated with the vehicle. A tail-bleeding assay was used to determine clopidogrel's effect on hemostasis. P2Y12 deficient mice were administered clopidogrel (10 mg/kg) or vehicle daily for five days before the procedure was performed. Bleeding was evaluated using a tail tip amputation assay. After tip amputation, the tail was quickly placed in a tube containing Drabkin’s reagent. Blood loss was determined by measuring the concentration of hemoglobin in the tube using a standard curve. P2Y12-deficient animals bled more (5.955 ± 1.159 g/dl) than their wildtype littermates (2.491 ± 0.962 g/dl). Importantly, our data demonstrated that clopidogrel treatment induced more bleeding in both the P2Y12-deficient mice (7.921 ± 1.015 g/dl) and wildtype mice (3.898 ± 0.324 g/dl) compared to drug vehicle. These results suggest that clopidogrel’s bleeding effect is not completely dependent on the P2Y12 receptor inhibition. Other elements in the hemostatic system, such as the vessel-related factors, could be responsible for the observed clopidogrel bleeding effects.

This work was funded in part by the ASPET Summer Undergraduate Research Fellowship.