The role of adenosine diphosphate mediated platelet responsiveness for the stability of platelet integrity in citrated whole blood under ex vivo conditions

Please always quote using this URN: urn:nbn:de:bvb:20-opus-159879
  • Background: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases. Platelets provided for research or for therapeutic use are frequently separated from citrated whole blood (WB) stored for different periods of time. Although functionally intact platelets are required, the stability of platelet integrity, e.g. adenosine diphosphate (ADP) mediated responsiveness, has never been thoroughly investigated in citrated WB under ex vivo conditions. Objectives:Background: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases. Platelets provided for research or for therapeutic use are frequently separated from citrated whole blood (WB) stored for different periods of time. Although functionally intact platelets are required, the stability of platelet integrity, e.g. adenosine diphosphate (ADP) mediated responsiveness, has never been thoroughly investigated in citrated WB under ex vivo conditions. Objectives: Platelet integrity was evaluated at different time points in citrated WB units, collected from healthy donors and stored for 5 days at ambient temperature. The analysis included the measurement of activation markers, of induced light transmission aggregometry and of purinergic receptor expression or function. Inhibitory pathways were explored by determination of basal vasodilator-stimulated phosphoprotein (VASP)-phosphorylation, intracellular cyclic nucleotide levels and the content of phosphodiesterase 5A. Fresh peripheral blood (PB) samples served as controls. Results: On day 5 of storage, thrombin receptor activating peptide-6 (TRAP-6) stimulated CD62P expression and fibrinogen binding were comparable to PB samples. ADP induced aggregation continuously decreased during storage. Purinergic receptor expression remained unchanged, whereas the P2Y1 activity progressively declined in contrast to preserved P2Y12 and P2X1 function. Inhibitory pathways were unaffected except for a slight elevation of VASP phosphorylation at Ser\(^{239}\) on day 5. Conclusion: After 5 days of storage in citrated WB, platelet responsiveness to TRAP-6 is sufficiently maintained. However, ADP-mediated platelet integrity is more sensitive to deterioration, especially after storage for more than 2 days. Decreasing ADP-induced aggregation is particularly caused by the impairment of the purinergic receptor P2Y1 activity. These characteristics should be considered in the use of platelets from stored citrated WB for experimental or therapeutic issues.show moreshow less

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Metadaten
Author: Juergen Koessler, Michaela Schwarz, Katja Weber, Julia Etzel, Angela Koessler, Markus Boeck, Anna Kobsar
URN:urn:nbn:de:bvb:20-opus-159879
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Transfusionsmedizin und Hämotherapie
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2017
Volume:12
Issue:11
Pagenumber:e0188193
Source:PLoS ONE 12(11): e0188193 (2017). DOI: 10.1371/journal.pone.0188193
DOI:https://doi.org/10.1371/journal.pone.0188193
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:blood; fibrinogen; flow cytometry; phosphorylation; platelets; specimen storage
Release Date:2018/03/29
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2017
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International