Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles

Patrick Burger, Elena Kostova, Esther Bloem, Petra Hilarius-Stokman, Alexander B Meijer, Timo K van den Berg, Arthur J Verhoeven, Dirk de Korte, Robin van Bruggen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

During storage, erythrocytes undergo changes that alter their clearance and function after transfusion and there is increasing evidence that these changes contribute to the complications observed in transfused patients. Stored erythrocytes were incubated overnight at 37°C to mimic the temperature after transfusion. After incubation, several markers for erythrocyte damage were analysed. After overnight incubation, stored erythrocytes showed increased potassium leakage, haemolysis, PS exposure and vesicle formation, and all these effects increased with increasing storage time. Furthermore, we demonstrated that long-term stored erythrocytes develop decreased flippase activity and increased scrambling activity after overnight incubation, leading to PS exposure and the release of vesicles. Reduced intracellular potassium was identified as the cause of the decreased flippase activity. Lastly, we provide evidence that erythrocytes can return to a PS-negative state by shedding parts of their membrane as PS-containing vesicles and that these vesicles can serve as a platform for the coagulation cascade. These findings reveal that potassium leakage, a well-known phenomenon of prolonged erythrocyte storage, primes erythrocytes for PS exposure. PS exposure will lead to vesicle formation and might have an important impact on the post-transfusion function and side effects of stored erythrocytes.

Original languageEnglish
Pages (from-to)377-86
Number of pages10
JournalBritish Journal of Haematology
Volume160
Issue number3
DOIs
Publication statusPublished - Feb 2013

Cite this

Burger, Patrick ; Kostova, Elena ; Bloem, Esther ; Hilarius-Stokman, Petra ; Meijer, Alexander B ; van den Berg, Timo K ; Verhoeven, Arthur J ; de Korte, Dirk ; van Bruggen, Robin. / Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles. In: British Journal of Haematology. 2013 ; Vol. 160, No. 3. pp. 377-86.
@article{8c801480ff8a4ddead7823694cd17c56,
title = "Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles",
abstract = "During storage, erythrocytes undergo changes that alter their clearance and function after transfusion and there is increasing evidence that these changes contribute to the complications observed in transfused patients. Stored erythrocytes were incubated overnight at 37°C to mimic the temperature after transfusion. After incubation, several markers for erythrocyte damage were analysed. After overnight incubation, stored erythrocytes showed increased potassium leakage, haemolysis, PS exposure and vesicle formation, and all these effects increased with increasing storage time. Furthermore, we demonstrated that long-term stored erythrocytes develop decreased flippase activity and increased scrambling activity after overnight incubation, leading to PS exposure and the release of vesicles. Reduced intracellular potassium was identified as the cause of the decreased flippase activity. Lastly, we provide evidence that erythrocytes can return to a PS-negative state by shedding parts of their membrane as PS-containing vesicles and that these vesicles can serve as a platform for the coagulation cascade. These findings reveal that potassium leakage, a well-known phenomenon of prolonged erythrocyte storage, primes erythrocytes for PS exposure. PS exposure will lead to vesicle formation and might have an important impact on the post-transfusion function and side effects of stored erythrocytes.",
keywords = "Blood Coagulation/drug effects, Blood Coagulation Factors/metabolism, Blood Preservation, Erythrocytes/chemistry, Hemolysis, Humans, Phosphatidylserines/analysis, Potassium/metabolism, Transport Vesicles/metabolism",
author = "Patrick Burger and Elena Kostova and Esther Bloem and Petra Hilarius-Stokman and Meijer, {Alexander B} and {van den Berg}, {Timo K} and Verhoeven, {Arthur J} and {de Korte}, Dirk and {van Bruggen}, Robin",
note = "{\circledC} 2012 Blackwell Publishing Ltd.",
year = "2013",
month = "2",
doi = "10.1111/bjh.12133",
language = "English",
volume = "160",
pages = "377--86",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",

}

Burger, P, Kostova, E, Bloem, E, Hilarius-Stokman, P, Meijer, AB, van den Berg, TK, Verhoeven, AJ, de Korte, D & van Bruggen, R 2013, 'Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles' British Journal of Haematology, vol. 160, no. 3, pp. 377-86. https://doi.org/10.1111/bjh.12133

Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles. / Burger, Patrick; Kostova, Elena; Bloem, Esther; Hilarius-Stokman, Petra; Meijer, Alexander B; van den Berg, Timo K; Verhoeven, Arthur J; de Korte, Dirk; van Bruggen, Robin.

In: British Journal of Haematology, Vol. 160, No. 3, 02.2013, p. 377-86.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Potassium leakage primes stored erythrocytes for phosphatidylserine exposure and shedding of pro-coagulant vesicles

AU - Burger, Patrick

AU - Kostova, Elena

AU - Bloem, Esther

AU - Hilarius-Stokman, Petra

AU - Meijer, Alexander B

AU - van den Berg, Timo K

AU - Verhoeven, Arthur J

AU - de Korte, Dirk

AU - van Bruggen, Robin

N1 - © 2012 Blackwell Publishing Ltd.

PY - 2013/2

Y1 - 2013/2

N2 - During storage, erythrocytes undergo changes that alter their clearance and function after transfusion and there is increasing evidence that these changes contribute to the complications observed in transfused patients. Stored erythrocytes were incubated overnight at 37°C to mimic the temperature after transfusion. After incubation, several markers for erythrocyte damage were analysed. After overnight incubation, stored erythrocytes showed increased potassium leakage, haemolysis, PS exposure and vesicle formation, and all these effects increased with increasing storage time. Furthermore, we demonstrated that long-term stored erythrocytes develop decreased flippase activity and increased scrambling activity after overnight incubation, leading to PS exposure and the release of vesicles. Reduced intracellular potassium was identified as the cause of the decreased flippase activity. Lastly, we provide evidence that erythrocytes can return to a PS-negative state by shedding parts of their membrane as PS-containing vesicles and that these vesicles can serve as a platform for the coagulation cascade. These findings reveal that potassium leakage, a well-known phenomenon of prolonged erythrocyte storage, primes erythrocytes for PS exposure. PS exposure will lead to vesicle formation and might have an important impact on the post-transfusion function and side effects of stored erythrocytes.

AB - During storage, erythrocytes undergo changes that alter their clearance and function after transfusion and there is increasing evidence that these changes contribute to the complications observed in transfused patients. Stored erythrocytes were incubated overnight at 37°C to mimic the temperature after transfusion. After incubation, several markers for erythrocyte damage were analysed. After overnight incubation, stored erythrocytes showed increased potassium leakage, haemolysis, PS exposure and vesicle formation, and all these effects increased with increasing storage time. Furthermore, we demonstrated that long-term stored erythrocytes develop decreased flippase activity and increased scrambling activity after overnight incubation, leading to PS exposure and the release of vesicles. Reduced intracellular potassium was identified as the cause of the decreased flippase activity. Lastly, we provide evidence that erythrocytes can return to a PS-negative state by shedding parts of their membrane as PS-containing vesicles and that these vesicles can serve as a platform for the coagulation cascade. These findings reveal that potassium leakage, a well-known phenomenon of prolonged erythrocyte storage, primes erythrocytes for PS exposure. PS exposure will lead to vesicle formation and might have an important impact on the post-transfusion function and side effects of stored erythrocytes.

KW - Blood Coagulation/drug effects

KW - Blood Coagulation Factors/metabolism

KW - Blood Preservation

KW - Erythrocytes/chemistry

KW - Hemolysis

KW - Humans

KW - Phosphatidylserines/analysis

KW - Potassium/metabolism

KW - Transport Vesicles/metabolism

U2 - 10.1111/bjh.12133

DO - 10.1111/bjh.12133

M3 - Article

VL - 160

SP - 377

EP - 386

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -