Transfusion of cold temperature storage platelets induces rapid clearance by hepatocytes and promotes the production of platelets.

Cold temperature (1-6°C) provides an option for long-term preservation of platelets, but its clinical application is limited because cold-stored platelets (CSPs) are rapidly removed after transfusion. The asialoglycoprotein receptor (ASGPR) in the liver plays a crucial role in the clearance of aged platelets and the rapid clearance of CSPs. We aimed to investigate the relationship between CSP clearance and ASGPR expression to provide support for expanding the clinical application of CSPs. The characteristics of CSPs were determined, and the binding and uptake of platelets by hepatocytes and Kupffer cells were analyzed. To investigate the mechanism of CSP removal, we performed platelet transfusion studies using splenectomies and macrophage clearance in ASGPR knockout mice. Finally, molecular biological tools were used to evaluate the signaling pathways involved in platelet biogenesis. CSPs exhibited low metabolic levels and enhanced hemostatic effects but was rapidly cleared following transfusion. The co-culture results showed that hepatocytes and Kupffer cells could phagocytose CSPs. However, increased desialylation of CSPs led to rapid clearance regulated by ASGPR expressed on hepatocytes, but not by those expressed on Kupffer cells. The elevated clearance rate of CSPs led to strong activation of JAK2-STAT3 signaling, thereby stimulating TPO production. Cold temperature storage improved platelet quality; however, the circulation time was reduced. This high clearance rate, which strongly stimulates TPO production, holds the potential to promote a more substantial increase in megakaryocytes and platelet neogenesis. These findings have implications for the future clinical use of CSPs.