Storage temperature determines platelet GPVI levels and function in mice and humans

Author:

Miles Jeffrey1,Bailey S. Lawrence1,Obenaus Ava M.2,Mollica Molly Y.3,Usaneerungrueng Chomkan1,Byrne Daire1,Fang Lydia1,Flynn Jake R.3,Corson Jill1,Osborne Barbara1,Houck Katie1,Wang Yi1,Shen Yu1,Fu Xiaoyun14,Dong Jing-Fei14ORCID,Sniadecki Nathan J.235ORCID,Stolla Moritz14ORCID

Affiliation:

1. Bloodworks Northwest Research Institute, Seattle, WA; and

2. Department of Mechanical Engineering,

3. Department of Bioengineering,

4. Division of Hematology, Department of Medicine, School of Medicine, and

5. Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA

Abstract

Abstract Platelets are currently stored at room temperature before transfusion to maximize circulation time. This approach has numerous downsides, including limited storage duration, bacterial growth risk, and increased costs. Cold storage could alleviate these problems. However, the functional consequences of cold exposure for platelets are poorly understood. In the present study, we compared the function of cold-stored platelets (CSP) with that of room temperature–stored platelets (RSP) in vitro, in vivo, and posttransfusion. CSP formed larger aggregates under in vitro shear while generating similar contractile forces compared with RSP. We found significantly reduced glycoprotein VI (GPVI) levels after cold exposure of 5 to 7 days. After transfusion into humans, CSP were mostly equivalent to RSP; however, their rate of aggregation in response to the GPVI agonist collagen was significantly lower. In a mouse model of platelet transfusion, we found a significantly lower response rate to the GPVI-dependent agonist convulxin and significantly lower GPVI levels on the surface of transfused platelets after cold storage. In summary, our data support an immediate but short-lived benefit of cold storage and highlight the need for thorough investigations of CSP. This trial was registered at www.clinicaltrials.gov as #NCT03787927.

Publisher

American Society of Hematology

Subject

Hematology

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