TY - JOUR

T1 - Comprehensive metabolomic study of platelets reveals the expression of discrete metabolic phenotypes during storage

AU - Paglia, Giuseppe

AU - Sigurjónsson, Ólafur E

AU - Rolfsson, Óttar

AU - Valgeirsdottir, Soley

AU - Hansen, Morten Bagge

AU - Brynjólfsson, Sigurður

AU - Gudmundsson, Sveinn

AU - Palsson, Bernhard O

N1 - © 2014 AABB.

PY - 2014/11

Y1 - 2014/11

N2 - BACKGROUND: Platelet (PLT) concentrates are routinely stored for 5 to 7 days. During storage they exhibit what has been termed PLT storage lesion (PSL), which is evident by a loss of hemostatic function when transfused into patients. The overall goal of this study was to obtain a comprehensive data set describing PLT metabolism during storage.STUDY DESIGN AND METHODS: The experimental approach adopted to achieve this goal combined a series of standard assays to monitor the quality of stored PLTs and a deep-coverage metabolomics study using liquid chromatography coupled with mass spectrometry performed on both the extracellular and the intracellular environments. During storage we measured 174 different variables in 6 PLT units, collected by apheresis. Samples were collected at eight different time points resulting in a data set containing more than 8000 measurements.RESULTS: Stored PLTs did not undergo a monotonic decay, but experienced systematic changes in metabolism reflected in three discrete metabolic phenotypes: The first (Days 0-3) was associated with active glycolysis, pentose phosphate pathway, and glutathione metabolism and down regulation of tricarboxylic acid (TCA) cycle. The second (Days 4-6) was associated with a more active TCA cycle as well as increased purine metabolism. A third metabolic phenotype of less clinical relevance (Days 7-10) was associated with a faster decay of cellular metabolism.CONCLUSION: PSL is not associated with a linear decay of metabolism, but rather with successive metabolic shifts. These findings may give new insight into the mechanisms underlying PSL and encourage the deployment of systems biology methods to PSL.

AB - BACKGROUND: Platelet (PLT) concentrates are routinely stored for 5 to 7 days. During storage they exhibit what has been termed PLT storage lesion (PSL), which is evident by a loss of hemostatic function when transfused into patients. The overall goal of this study was to obtain a comprehensive data set describing PLT metabolism during storage.STUDY DESIGN AND METHODS: The experimental approach adopted to achieve this goal combined a series of standard assays to monitor the quality of stored PLTs and a deep-coverage metabolomics study using liquid chromatography coupled with mass spectrometry performed on both the extracellular and the intracellular environments. During storage we measured 174 different variables in 6 PLT units, collected by apheresis. Samples were collected at eight different time points resulting in a data set containing more than 8000 measurements.RESULTS: Stored PLTs did not undergo a monotonic decay, but experienced systematic changes in metabolism reflected in three discrete metabolic phenotypes: The first (Days 0-3) was associated with active glycolysis, pentose phosphate pathway, and glutathione metabolism and down regulation of tricarboxylic acid (TCA) cycle. The second (Days 4-6) was associated with a more active TCA cycle as well as increased purine metabolism. A third metabolic phenotype of less clinical relevance (Days 7-10) was associated with a faster decay of cellular metabolism.CONCLUSION: PSL is not associated with a linear decay of metabolism, but rather with successive metabolic shifts. These findings may give new insight into the mechanisms underlying PSL and encourage the deployment of systems biology methods to PSL.

KW - Blood Platelets

KW - Blood Preservation

KW - Citric Acid Cycle

KW - Female

KW - Gene Expression Regulation

KW - Glutathione

KW - Humans

KW - Male

KW - Metabolome

KW - Metabolomics

KW - Pentose Phosphate Pathway

KW - Time Factors

U2 - 10.1111/trf.12710

DO - 10.1111/trf.12710

M3 - Journal article

C2 - 24840017

VL - 54

SP - 2911

EP - 2923

JO - Transfusion

JF - Transfusion

SN - 0041-1132

IS - 11

ER -