Pyrophosphate as a novel anticoagulant for storage of whole blood: A proof-of-concept study.
anticoagulation
blood storage
citrate
platelets
pyrophosphate
transfusion
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
29
03
2023
received:
08
02
2023
accepted:
28
04
2023
medline:
14
7
2023
pubmed:
29
5
2023
entrez:
29
5
2023
Statut:
ppublish
Résumé
Citrate is the only anticoagulant currently Food and Drug Administration (FDA)-approved for the long-term storage of blood for transfusion. Citrate inhibits phosphofructokinase and may play a pro-inflammatory role, suggesting that there may be an advantage to using alternative anticoagulants. Here, we examine the use of pyrophosphate as an anticoagulant. Whole blood samples from healthy donors were anticoagulated either with citrate-phosphate-adenine-dextrose (CPDA-1) or our novel anticoagulant mixture pyrophosphate-phosphate-adenine-dextrose (PPDA-1). Samples were assessed for coagulation capacity by thromboelastography immediately after anticoagulation (T0) with and without recalcification, as well as 5 hours after anticoagulation (T1) with recalcification. Complete blood counts were taken at both timepoints. Flow cytometry to evaluate platelet activation as well as blood smears to evaluate cellular morphology were performed at T1. No clotting was detected in samples anticoagulated with either solution without recalcification. After recalcification, clotting function was restored in both groups. R-Time in recalcified PPDA-1 samples was shorter than in CPDA-1 samples. A reduction in platelet count at T1 compared to T0 was observed in both groups. No significant platelet activation was observed in either group at T1. Blood smear indicated platelet clumping in PPDA-1. We have shown initial proof of concept that pyrophosphate functions as an anticoagulant at the dose used in this study, though there is an associated loss of platelets over time that may limit its usefulness for blood storage. Further dose optimization of pyrophosphate may limit or reduce the loss of platelets.
Sections du résumé
BACKGROUND
Citrate is the only anticoagulant currently Food and Drug Administration (FDA)-approved for the long-term storage of blood for transfusion. Citrate inhibits phosphofructokinase and may play a pro-inflammatory role, suggesting that there may be an advantage to using alternative anticoagulants. Here, we examine the use of pyrophosphate as an anticoagulant.
STUDY DESIGN AND METHODS
Whole blood samples from healthy donors were anticoagulated either with citrate-phosphate-adenine-dextrose (CPDA-1) or our novel anticoagulant mixture pyrophosphate-phosphate-adenine-dextrose (PPDA-1). Samples were assessed for coagulation capacity by thromboelastography immediately after anticoagulation (T0) with and without recalcification, as well as 5 hours after anticoagulation (T1) with recalcification. Complete blood counts were taken at both timepoints. Flow cytometry to evaluate platelet activation as well as blood smears to evaluate cellular morphology were performed at T1.
RESULTS
No clotting was detected in samples anticoagulated with either solution without recalcification. After recalcification, clotting function was restored in both groups. R-Time in recalcified PPDA-1 samples was shorter than in CPDA-1 samples. A reduction in platelet count at T1 compared to T0 was observed in both groups. No significant platelet activation was observed in either group at T1. Blood smear indicated platelet clumping in PPDA-1.
CONCLUSION
We have shown initial proof of concept that pyrophosphate functions as an anticoagulant at the dose used in this study, though there is an associated loss of platelets over time that may limit its usefulness for blood storage. Further dose optimization of pyrophosphate may limit or reduce the loss of platelets.
Substances chimiques
CPDA solutions
0
Anticoagulants
0
diphosphoric acid
4E862E7GRQ
Diphosphates
0
Citrates
0
Glucose
IY9XDZ35W2
Adenine
JAC85A2161
Phosphates
0
citrate phosphate dextrose
51404-37-6
Citric Acid
2968PHW8QP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1392-1398Informations de copyright
© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.
Références
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