Platelet storage failure-Metformin as causative agent
Abstract
BACKGROUND: Pathogen reduction technology (PRT)-treated apheresis platelets (APs) were returned without platelet swirl and with pH22°C < 6.2. The platelet donor was taking prescription levothyroxine and metformin plus over-the-counter medications and supplements. We hypothesized that either PRT or medication was causative.
STUDY DESIGN AND METHODS: One AP from a double AP collection from this donor was PRT-treated, the other unit untreated. Units were assessed over 7-day storage with a standard panel of platelet assays and metabolomics using high resolution mass spectrometry. The dose effect of metformin on platelets over storage was evaluated in vitro using APs obtained from non-medicated donors.
RESULTS: This donor's PRT- and non-PRT treated paired units had pH values <6.2 by the end of day 2. Lactate generation rates in the PRT- and non-PRT units were very high compared to previously reported values and approached that reported for anaerobic storage. Metabolomic analysis revealed impairments in a number of energy metabolic pathways between PRT- and non-PRT platelets; however, this did not support a major causative role of PRT in the significant upregulation of lactic acid production. Metformin caused a dose-dependent upregulation of glycolysis, resulting in pH decline.
DISCUSSION: We conclude that metformin is the most likely cause for this donor's stored platelet pH failures. Metformin is commonly used to treat type 2 diabetes and is not a donor deferral medication.…
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