Platelet Storage Lesion Accelerates Desialylation of Platelets and Increases Hepatic Thrombopoietin Production

Abstract

Background: Stored platelets undergo deleterious changes, referred to as platelet storage lesions (PSLs), which accelerate the desialylation of platelets and result in their phagocytosis and clearance by hepatic macrophages. Recent studies have reported that Ashwell-Morell receptor binds to desialylated platelets, thereby inducing hepatic thrombopoietin (TPO) production in a mouse model. Therefore, this study aimed to demonstrate these relationships between PSL and hepatic TPO production in human study. Methods: Platelet concentrates (PCs) were obtained from 5 healthy volunteers and remaining samples in blood bank. PCs were divided into two halves, and stored either at 22°C or 4°C. Experiments were conducted using serial samples. Desialylation was assessed using flow cytometry, and structural changes were visualized using electron microscopy. Following co-culture of HepG2 cells (HB-8065, ATCC) with isolated platelets, hepatic TPO production was determined using real-time quantitative polymerase chain reaction (qPCR) and the supernatant TPO level was measured using a Luminex kit. Results: For 5 days of storage duration, platelet counts themselves were not influenced by the storage conditions. The degree of desialylation was proportional to the storage duration and dependent on hypothermal stress. Changes on platelet surface and structure in electron microscope were significant according to storage conditions. And HepG2 cells that reacted with aged or refrigerated platelets expressed more TPO mRNA than those that reacted with fresh platelets. But, the changes of supernatant TPO level were not significant. Conclusions: This study demonstrated that, in vitro, aging and refrigeration affect the integrity of human platelets, resulting in induction of hepatic TPO mRNA expression, as proven in a mouse model.