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Published on: April 9, 2018
The Effect of Leukocyte Removal and Matrix Metalloproteinase Inhibition on Platelet Storage Lesions
Alina Rak-Pasikowska1, Kornela Hałucha1,2, Agnieszka Sapa-Wojciechowska1
1Division of Clinical Chemistry and Laboratory Haematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A St., 50-556 Wrocław, Poland.
Abstract:
The reasons for unfavorable changes in platelet concentrate (PC) quality during storage are not fully understood yet. We aimed to evaluate whether leukocytes and matrix metalloproteinases (MMPs) lead to a decrease in the quality of PCs and examine whether MMP inhibition will slow down the platelets' aging. Nine PCs were divided into three parts: (1) leukocyte-depleted (F) PCs, (2) PCs with no additional procedures (NF), and (3) PCs with the addition of an MMP inhibitor-doxycycline (D). Each PC was stored for 144 h, and a sample for testing was separated from each part on the day of preparation and after 24, 48, 72 and 144 h of storage. Blood morphological analysis, platelet aggregation, and the expression of activation markers were evaluated. MMP-2 and MMP-9 concentration, activity, and gene expression were assessed. Platelet aggregation decreased, and platelet activation marker expression increased during the storage. D concentrates showed the lowest level of platelet activation. In turn, leukocyte-depleted PCs showed the highest level of platelet activation in general. MMP-9 platelet activity was higher in leukocyte-containing concentrates at the end of the storage period. We concluded that the filtration process leads to a higher platelet activation level. The presence of doxycycline in PCs reduces the expression of the activation markers as compared to leukocyte-depleted concentrates.
Insights
Leukocytes and matrix metalloproteinases (MMPs) impact platelet concentrate (PC) quality during storage. Inhibiting MMPs with doxycycline slowed platelet aging and activation, preserving PC quality.
Area of Science:
- Transfusion Medicine
- Hematology
- Biochemistry
Background:
- Platelet concentrate (PC) quality deteriorates during storage, but the underlying mechanisms involving leukocytes and matrix metalloproteinases (MMPs) are not fully elucidated.
- Understanding these factors is crucial for improving transfusion safety and efficacy.
Purpose of the Study:
- To investigate the role of leukocytes and MMPs in the decline of PC quality during storage.
- To assess the efficacy of MMP inhibition using doxycycline in mitigating platelet aging and activation.
Main Methods:
- Nine PCs were processed into three groups: leukocyte-depleted (F), untreated (NF), and doxycycline-treated (D).
- Samples were analyzed over 144 hours for morphology, platelet aggregation, activation markers, and MMP-2/MMP-9 levels (concentration, activity, gene expression).
Main Results:
- Platelet aggregation decreased, while activation markers increased during storage.
- Doxycycline-treated (D) PCs exhibited the lowest platelet activation, whereas leukocyte-depleted (F) PCs showed the highest.
- MMP-9 activity was elevated in leukocyte-containing PCs at storage end.
Conclusions:
- Leukocyte filtration increases platelet activation levels in PCs.
- Doxycycline effectively reduces platelet activation markers in PCs, suggesting MMP inhibition can slow platelet aging and preserve quality.
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