Combined host disruption of macrophage- and hepatocyte-mediated clearance phenocopies the effect of R- and S-G04 on the clearance of cold-stored platelets. (A) Schematic experimental design for the in vivo preclinical model of platelet survival analysis with AMR inhibitor. (B) Recovery of 10-day stored human platelets transfused to clodronate-treated, sublethally irradiated thrombocytopenic NSG immunodeficient mice after asialofetuin treatment. Wash step: rewarming for 15 minutes followed by the wash step and rest for another 15 minutes at RT. (C) AUC of data depicted in panel B. (D) Schematic experimental design for the in vivo preclinical model of platelet survival analysis with AMR inhibitor and macrophage depletion. (E) Survival of 10-day stored human platelets transfused to clodronate-treated, sublethally irradiated thrombocytopenic NSG immunodeficient mice with clodronate liposomes and asialofetuin treatment. (F) AUC of data depicted in panel E. Wash step includes rewarming for 15 minutes followed by the wash step and rest for another 15 minutes at RT. For each experiment, data include a minimum of 4 mice per group in each of the 2 independent experiments. #P = .06; ∗∗∗P < .001.