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Permanent lesions of stored platelets correlate to pH and cell count while reversible lesions do not
1Department of Biochemistry, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
Insights
Platelet storage lesion impacts function, with pH causing permanent damage detectable in washed platelets. A reversible lesion also affects platelet-rich plasma, highlighting the need for pH regulation in stored platelet concentrates.
Area of Science:
- Hematology
- Biotechnology
- Biochemistry
Background:
- Increasing demand for stored platelet concentrates (PC) necessitates understanding factors affecting platelet function during storage.
- The platelet storage lesion (PSL) encompasses various factors that reduce platelet viability and therapeutic efficacy over time.
- Recent research focuses on the role of storage medium pH in exacerbating the PSL.
Purpose of the Study:
- To investigate the impact of storage medium pH on platelet function and the development of the platelet storage lesion.
- To differentiate between reversible and irreversible components of the PSL affecting platelet aggregation.
- To assess the influence of washing on stored platelet function and its correlation with storage pH.
Main Methods:
- Stored platelet concentrates (PC) were compared to fresh platelets (platelet-rich plasma [PRP] and washed platelets).
- Platelet function was assessed by measuring aggregation induced by specific agonists (U46619/epinephrine, SFLLRNP, thrombin).
- Storage pH and platelet count were measured; aggregation responses of PRP and washed platelets were analyzed.
Main Results:
- Platelet aggregation was significantly impaired in stored PRP after 6-7 days, but partially restored upon washing.
- Washing restored platelet activity, suggesting a reversible component of the PSL in PRP.
- Aggregation of washed platelets correlated significantly with storage pH, indicating a permanent pH-induced lesion, while PRP aggregation did not correlate with pH.
Conclusions:
- Storage pH is a critical factor contributing to a permanent platelet storage lesion, detectable in washed platelets.
- A partially reversible lesion also affects platelet function in stored PRP.
- Maintaining optimal pH is crucial for preserving the therapeutic value of stored platelet concentrates, even in advanced storage containers.
Abstract:
The demand for stored platelet concentrates (PC) for therapeutic transfusions has been increasing for the past three decades. Loss of platelet functionality increases with the length of storage time due to a multitude of factors collectively referred to as a platelet storage lesion. As more of the causes of the storage lesion have been defined, storage conditions have improved along with the therapeutic value of the transfused platelet samples. This report addressed new aspects of the storage lesion correlated with the pH of the storage medium. Platelet function was evaluated as aggregation induced by the synergistic agonist pair, U46619 (TXA2 mimetic) plus epinephrine or the strong agonists SFLLRNP (a peptide thrombin receptor agonist) or thrombin each added alone. Stored PC were compared to freshly prepared platelets as platelet-rich plasma (PRP) or washed platelets re-suspended in hepes Tyrode's buffer. The pH of the storage plasma, was inversely proportional to the cell count with platelets stored for 6 days. Agonist-induced platelet aggregation was significantly impaired by storage for 6-7 days as PRP; however, upon washing, a significant level of activity was restored. Washed platelets more accurately reflect conditions of transfused platelets that may regain activity in vivo. There appeared to be two subpopulations of stored PRP samples--one that retained activity and one that lost virtually all activity with the agonists tested. However, the lack of response to agonist observed with one subpopulation was reversed to the same level obtained with the active subpopulation upon washing. The subpopulation of stored PRP samples that were inactive with U46619-plus-epinephrine did not correspond to the subpopulation of samples that were nonresponsive to SFLLRNP, indicating that loss of activity with selected samples was possibly receptor specific. Loss of agonist-induced aggregation with PRP samples did not correlate with storage pH; however, the level of aggregation with washed platelets correlated significantly with pH. Results implied that pH caused a permanent storage lesion that could only be detected with washed platelets. A partially reversible lesion was superimposed on the pH lesion and was only detectable with PRP samples. Results indicate that continued attention must be paid to regulate the pH of stored PC even in the second generation plastic bags.