ABCC4 interacts with phosphodiesterase to affect aggregation and bleeding time. (A) Model depicting how ABCC4 affects platelet cAMP (yellow circle) and aggregation after treatment with the PDE2 inhibitor, EHNA. (B) ABCC4 function was assessed with a PMEA accumulation assay conducted in the presence and absence of either EHNA or (C) the bona fide ABCC4 inhibitor, MK571, using Abcc4 WT and KO-derived MEF cell lines (P < .05) (n = 5). (D) Maximum platelet aggregation of Abcc4 WT and KO platelets after blocking PDE2 activity with various concentrations of EHNA. (E) Lag time in Abcc4 WT and KO platelet aggregation after blocking PDE2 activity with EHNA. (F) Mice were treated with either vehicle or EHNA, and tail bleeding time was determined 30 minutes after drug administration. Abcc4 WT (n = 7) and Abcc4 KO (n = 5) (*P value < .01). The platelet aggregation data were derived from experiments performed at least 3 times using pooled PRP derived from 3 to 5 mice for each genotype. P < .05. Untxt, untreated.