Immunodeficient mouse model with repeated blood withdrawal and large-volume human platelet transfusion for evaluating hemostatic efficacy of cold-stored platelets

Preclinical evaluation of novel platelet products requires an animal model that supports large-volume human platelet transfusion and achieves a high proportion of circulating human platelets. We developed a novel immunodeficient mouse model with repeated blood withdrawal and large-volume transfusion of human platelet concentrates suspended in platelet additive solution (PAS-PCs). The mice tolerated cumulative blood withdrawal of approximately 50 mL/kg and human PAS-PC transfusion volumes exceeding 50 mL/kg. We compared cold-stored and room temperature (RT)-stored PAS-PCs after 3–5, 7–9, and 10–14 days of storage in 60 mice (10 mice per group). In same-duration comparisons, hemostasis times were significantly shorter with cold-stored platelets than with RT-stored platelets after 3–5 days ( P = 0.034) and 10–14 days ( P = 0.003) of storage, with no significant difference after 7–9 days ( P = 0.437). In contrast, circulating human platelet concentrations after transfusion were lower with cold-stored platelets after 3–5 days ( P = 0.007) and 7–9 days ( P = 0.001) of storage. This model enables large-volume human platelet transfusion while simultaneously evaluating hemostatic efficacy and circulating human platelet concentrations in the same mice.