Platelet Preservation Composition for Extended Storage
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Solution Overview
Problem
Current methods for storing human blood platelets result in storage-mediated lesions, leading to reduced functional capacity and persistence in circulation, limiting their shelf life to 5 days or fewer due to morphological changes, activation, and microvesiculation, which restricts their availability for transfusions.
Innovation Solution
A composition comprising a physiological salt solution, glutathione, ascorbic acid, adenosine, dichloroacetate, and less than 1 µM calcium ions, with a pH of 7 to 7.7, which decreases storage-mediated lesions and extends the storage time of platelets up to 15 days without attenuating hemostatic function, allowing storage at both ambient and sub-ambient temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If platelets are stored using conventional methods (additive solutions, reduced temperature, cryopreservation), then storage duration can be extended, but storage-mediated lesions accumulate leading to reduced functional capacity and rapid elimination from circulation
Solution Approach 1:
The invention changes multiple parameters of the storage solution simultaneously: pH (7.4-7.6, slightly alkaline), calcium concentration (<1 µM, severely restricted), and adds specific antioxidants (glutathione 0.1-10 mM, ascorbic acid 0.1-10 mM). These parameter changes create an environment that suppresses storage lesions while maintaining platelet viability for extended periods (5-10 days or more), resolving the contradiction between storage duration and functional capacity
Solution Approach 2:
The storage solution is a composite formulation combining physiological salt solution with multiple protective agents: glutathione (antioxidant), ascorbic acid (antioxidant), adenosine (energy source), and severely restricted calcium ions. This composite approach provides synergistic protection against storage-mediated lesions, maintaining both extended storage duration and reliable functional capacity
2Use of energy by moving object
If platelets are stored at ambient temperature (25 °C), then metabolic activity is maintained, but storage-mediated lesions develop more rapidly compared to reduced temperature storage
Solution Approach 1:
The storage solution contains preliminary protective agents (glutathione and ascorbic acid antioxidants) that act in advance to prevent storage-mediated lesions before they can develop. This preliminary anti-action allows platelets to maintain metabolic activity at ambient temperature without suffering the usual rapid accumulation of storage lesions, resolving the contradiction between metabolic activity and lesion development
3Loss of time
If storage time is extended beyond 5 days, then platelet availability increases, but the majority of platelets are quickly eliminated from circulation due to storage lesions
Solution Approach 1:
By changing the storage parameters (pH 7.4-7.6, <1 µM calcium, added antioxidants), the invention extends safe storage duration to 5-10 days or more while maintaining platelet quality. This resolves the contradiction by allowing extended storage time without the usual loss of platelet persistence in circulation, as the modified parameters prevent the storage lesions that would otherwise cause rapid elimination
Data Source
Figure 1A~1B
Figure 2
Figure 3A
AI summary
Provided herein, inter alia, are compositions and methods for preserving platelets in a lesion-free and functional state during extended storage periods of up to 15 days as well as methods and kits for utilizing the same. In contrast to currently available compositions and techniques for preserving platelets, platelets stored in the compositions disclosed herein are characterized by a marked decrease in "storage-lesions," which are associated with attenuated hemostatic function. During platelet storage, the compositions disclosed herein (1) maintain and/or restore platelet energy states and morphology; (2) maintain active metabolism and buffering; (3) preserve and/or promote nitric oxide production; and (4) prevent microparticle formation, aggregation and activation during storage. As such, long term preservation in the compositions described herein produce platelets that are fully functional and lesion-free.