Platelet storage failure-Metformin as causative agent

Pathogen reduction technology (PRT)-treated apheresis platelets (APs) were returned without platelet swirl and with pH_22°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.

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.

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.

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. Further investigation is indicated into the potential impact of metformin on platelet storage characteristics, the potential implications for medication deferral, and the need for additional screening tools in the laboratory.