Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions

Platelet storage is associated with storage lesions, including platelet morphological changes and a gradual functional loss. We investigated the impact of complement C3 inhibition on complement activation and platelet storage lesions in clinical platelet concentrates. Platelet concentrates (n = 8) w...

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Main Authors: Linnea I. Andersson, Per Sandgren, Dick J. Sjöström, Camilla Mohlin, Kim Hägerström, Ivar Tjernberg, Tom Eirik Mollnes, Per H. Nilsson
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Platelets
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Online Access:https://www.tandfonline.com/doi/10.1080/09537104.2025.2513298
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author Linnea I. Andersson
Per Sandgren
Dick J. Sjöström
Camilla Mohlin
Kim Hägerström
Ivar Tjernberg
Tom Eirik Mollnes
Per H. Nilsson
author_facet Linnea I. Andersson
Per Sandgren
Dick J. Sjöström
Camilla Mohlin
Kim Hägerström
Ivar Tjernberg
Tom Eirik Mollnes
Per H. Nilsson
author_sort Linnea I. Andersson
collection DOAJ
description Platelet storage is associated with storage lesions, including platelet morphological changes and a gradual functional loss. We investigated the impact of complement C3 inhibition on complement activation and platelet storage lesions in clinical platelet concentrates. Platelet concentrates (n = 8) were prepared in PAS-E and stored for seven days at 22°C. Each concentrate was split in two, with the C3 inhibitor compstatin Cp40 added to one part, and the other serving as the control. Complement and platelet activation markers, platelet function, and metabolic measures were analyzed every second day. Cp40 significantly reduced C3bc and sC5b-9 levels, but not C4c, indicating inhibition of complement activation at the level of C3. However, Cp40 did not affect platelet-specific or metabolic measures. Surface expression of CD62P and NAP-2 release increased significantly over the storage time, whereas CD63 expression and PF4 and TSP-1 release remained stable. Platelet responses to TRAP-6 mediated PAR-1 activation and U46619 mediated TXA2R stimulation decreased over time, recorded as CD62P and CD63 expression and release of soluble factors. No drop in platelet count was observed, and metabolic markers remained within their critical limits. While C3 inhibition effectively reduced complement activation in stored platelet concentrates, it did not mitigate platelet storage lesions.
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spelling doaj-art-ad43d0fac916478e91d5a374aeb8f0dd2025-08-20T03:24:00ZengTaylor & Francis GroupPlatelets0953-71041369-16352025-12-0136110.1080/09537104.2025.2513298Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesionsLinnea I. Andersson0Per Sandgren1Dick J. Sjöström2Camilla Mohlin3Kim Hägerström4Ivar Tjernberg5Tom Eirik Mollnes6Per H. Nilsson7Department of Chemistry and Biomedicine, Linnaeus University, Kalmar, SwedenCenter for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Stockholm, SwedenDepartment of Chemistry and Biomedicine, Linnaeus University, Kalmar, SwedenDepartment of Chemistry and Biomedicine, Linnaeus University, Kalmar, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Region Kalmar County, Kalmar, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Region Kalmar County, Kalmar, SwedenDepartment of Immunology, Oslo University Hospital and University of Oslo, Oslo, NorwayDepartment of Chemistry and Biomedicine, Linnaeus University, Kalmar, SwedenPlatelet storage is associated with storage lesions, including platelet morphological changes and a gradual functional loss. We investigated the impact of complement C3 inhibition on complement activation and platelet storage lesions in clinical platelet concentrates. Platelet concentrates (n = 8) were prepared in PAS-E and stored for seven days at 22°C. Each concentrate was split in two, with the C3 inhibitor compstatin Cp40 added to one part, and the other serving as the control. Complement and platelet activation markers, platelet function, and metabolic measures were analyzed every second day. Cp40 significantly reduced C3bc and sC5b-9 levels, but not C4c, indicating inhibition of complement activation at the level of C3. However, Cp40 did not affect platelet-specific or metabolic measures. Surface expression of CD62P and NAP-2 release increased significantly over the storage time, whereas CD63 expression and PF4 and TSP-1 release remained stable. Platelet responses to TRAP-6 mediated PAR-1 activation and U46619 mediated TXA2R stimulation decreased over time, recorded as CD62P and CD63 expression and release of soluble factors. No drop in platelet count was observed, and metabolic markers remained within their critical limits. While C3 inhibition effectively reduced complement activation in stored platelet concentrates, it did not mitigate platelet storage lesions.https://www.tandfonline.com/doi/10.1080/09537104.2025.2513298Complementcomplement inhibitionplatelet concentratesplatelet storage lesionsplatelet transfusionplatelets
spellingShingle Linnea I. Andersson
Per Sandgren
Dick J. Sjöström
Camilla Mohlin
Kim Hägerström
Ivar Tjernberg
Tom Eirik Mollnes
Per H. Nilsson
Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
Platelets
Complement
complement inhibition
platelet concentrates
platelet storage lesions
platelet transfusion
platelets
title Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
title_full Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
title_fullStr Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
title_full_unstemmed Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
title_short Complement C3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
title_sort complement c3 inhibition reduces complement activation in clinical platelet concentrates but does not counteract platelet storage lesions
topic Complement
complement inhibition
platelet concentrates
platelet storage lesions
platelet transfusion
platelets
url https://www.tandfonline.com/doi/10.1080/09537104.2025.2513298
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