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Complement activation and change of platelet phenotype during seven-day storage of clinical platelet concentrates
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. (Host Response to Biomaterials)ORCID iD: 0009-0002-0295-2120
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Sustainable development
SDG 3: Ensure healthy lives and promote well-being for all at all ages
Abstract [en]

As soon as blood leaves the human body, stress to the host´s protective cellular and protein cascades begin. My thesis focuses on the immune system, specifically the complement system and platelets, primarily known for their hemostatic properties but also play a role in immune responses. The core of this thesis is the interaction between the complement system and platelets in platelet concentrates destined for transfusion. Storing blood products, particularly platelet concentrates, presents challenges, including the development of platelet storage lesions. These lesions involve a series of biochemical, structural, and functional changes from when platelets are collected to when they are transfused, potentially leading to impaired platelet function and adverse transfusion reactions. For inventory management, the oldest platelet concentrates are typically used first for transfusion. Understanding the interplay between the complement system and platelets during storage is crucial for improving the quality of platelet concentrates for selecting optimal concentrates based on the indication. This thesis includes several exploratory studies: one examining the complement system and platelet function over storage time, another investigating the impact of complement inhibition with the aim to reduce platelet storage lesions, and a third exploring the ability of platelets to release mediators that can modulate an immune response when supplemented to thrombocytopenic blood. Additionally, one study examines the impact of blood collection tube composition on complement functional and activation analysis. I found that increased storage time was associated with increased complement activation, increased platelet activation and attenuated platelet function. However, there was no causal relationship between complement and platelet activation since complement inhibition did not alter platelet activation or function. Further, I found that platelets release mediators that could modulate an inflammatory reaction, but the storage time had only minor effect on the immunomodulatory effect. Last, I found that the composition of blood collection tubes significantly affected complement activation. While these findings may not immediately benefit patients, they provide new insights into platelet concentrates, highlighting the role of the complement system. Further research is needed to to understand the interaction between these components fully.

Place, publisher, year, edition, pages
Kalmar: Linnaeus University Press, 2024. , p. 132
Series
Linnaeus University Dissertations ; 552
Keywords [en]
Complement system, Platelets, Platelet concentrates, Biomaterial, Blood collection tubes, Complement inhibition
National Category
Immunology
Research subject
Natural Science, Chemistry
Identifiers
URN: urn:nbn:se:lnu:diva-133504DOI: 10.15626/LUD.552.2024ISBN: 9789180822343 (print)ISBN: 9789180822350 (electronic)OAI: oai:DiVA.org:lnu-133504DiVA, id: diva2:1915302
Public defence
2024-12-13, Umbra Cu4026, Kalmar, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 2018-04087Available from: 2024-11-25 Created: 2024-11-22 Last updated: 2024-11-25Bibliographically approved
List of papers
1. Storage of Transfusion Platelet Concentrates is Associated with Complement Activation and Reduced Ability of Platelets to Respond to Protease-Activated Receptor-1 and Thromboxane A2 Receptor
Open this publication in new window or tab >>Storage of Transfusion Platelet Concentrates is Associated with Complement Activation and Reduced Ability of Platelets to Respond to Protease-Activated Receptor-1 and Thromboxane A2 Receptor
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2024 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 2, article id 1091Article in journal (Refereed) Published
Abstract [en]

Platelet activation and the complement system are mutually dependent. Here, we investigated the effects of storage time on complement activation and platelet function in routinely produced platelet concentrates. The platelet concentrates (n = 10) were stored at 22 degrees C for seven days and assessed daily for complement and platelet activation markers. Additionally, platelet function was analyzed in terms of their responsiveness to protease-activated receptor-1 (PAR-1) and thromboxane A2 receptor (TXA(2)R) activation and their capacity to adhere to collagen. Complement activation increased over the storage period for all analyzed markers, including the C1rs/C1-INH complex (fold change (FC) = 1.9; p < 0.001), MASP-1/C1-INH complex (FC = 2.0; p < 0.001), C4c (FC = 1.8, p < 0.001), C3bc (FC = 4.0; p < 0.01), and soluble C5b-9 (FC = 1.7, p < 0.001). Furthermore, the levels of soluble platelet activation markers increased in the concentrates over the seven-day period, including neutrophil-activating peptide-2 (FC = 2.5; p < 0.0001), transforming growth factor beta 1 (FC = 1.9; p < 0.001) and platelet factor 4 (FC = 2.1; p < 0.0001). The ability of platelets to respond to activation, as measured by surface expression of CD62P and CD63, decreased by 19% and 24% (p < 0.05) for PAR-1 and 69-72% (p < 0.05) for TXA(2)R activation, respectively, on Day 7 compared to Day 1. The extent of platelet binding to collagen was not significantly impaired during storage. In conclusion, we demonstrated that complement activation increased during the storage of platelets, and this correlated with increased platelet activation and a reduced ability of the platelets to respond to, primarily, TXA(2)R activation.

Place, publisher, year, edition, pages
MDPI, 2024
Keywords
platelet storage, platelet storage lesion, complement activation, platelet function, hemostasis
National Category
Immunology Cell Biology
Research subject
Biomedical Sciences, Immunology; Natural Science, Cell and Organism Biology
Identifiers
urn:nbn:se:lnu:diva-127877 (URN)10.3390/ijms25021091 (DOI)001152950800001 ()38256162 (PubMedID)2-s2.0-85183338259 (Scopus ID)
Available from: 2024-02-20 Created: 2024-02-20 Last updated: 2024-11-25Bibliographically approved

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1231 of 3
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Citation style
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