Pathogen-Inactivated Cryoprecipitate for Extended Post-Thaw Use
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Solution Overview
Problem
Current methods for preparing cryoprecipitate are limited by time constraints for transfusion, potential pathogen growth, and the need for pooling, leading to product waste and increased costs, with existing compositions having limited post-thaw duration and variable fibrinogen content.
Innovation Solution
A pathogen-inactivated cryoprecipitate composition is prepared by treating plasma with amotosalen and UVA light, allowing it to be stored at room temperature for extended periods after thawing, maintaining biological activity and safety for infusion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If cryoprecipitate is prepared and stored according to current guidelines, then safety and biological activity are maintained, but the usable duration is limited to 6-24 hours post-thaw, resulting in product waste and increased costs
Solution Approach 1:
The plasma is treated with amotosalen and exposed to UVA light before freezing and cryoprecipitate formation. This preliminary pathogen inactivation treatment allows the final product to be stored at room temperature for extended periods (up to 168 hours) without pathogen growth, eliminating the need for rapid transfusion and reducing product waste
Solution Approach 2:
The invention changes the chemical state of the plasma by incorporating amotosalen, a photosensitizing agent. This parameter change enables the plasma to undergo photochemical modification when exposed to UVA light, creating a stable, pathogen-inactivated product that maintains biological activity for extended periods without refrigeration
2Quantity of substance
If cryoprecipitate is prepared with sufficient fibrinogen content to meet transfusion requirements, then therapeutic efficacy is ensured, but pooling of multiple units is required, increasing complexity and time constraints
Solution Approach 1:
The invention modifies the plasma composition by adding amotosalen and exposing it to UVA light, creating photochemically modified plasma. When cryoprecipitate is formed from this modified plasma, it contains sufficient fibrinogen (≥150 mg/unit) to meet transfusion requirements without requiring pooling, simplifying the transfusion process
Solution Approach 2:
The plasma is pre-treated with amotosalen and UVA light exposure before cryoprecipitate formation. This preliminary action ensures that the resulting cryoprecipitate units have consistent, sufficient fibrinogen content and extended stability, eliminating the need for post-thaw pooling
3Reliability
If cryoprecipitate is transfused within the recommended time frame, then safety is maintained, but Factor VIII activity decreases rapidly and product must be discarded, increasing costs
Solution Approach 1:
The plasma is treated with amotosalen and exposed to UVA light before freezing and cryoprecipitate formation. This preliminary pathogen inactivation treatment allows the final product to be stored at room temperature for extended periods (up to 168 hours) without pathogen growth, eliminating the need for rapid transfusion and reducing product waste
Solution Approach 2:
The invention converts the normally harmful effect of room temperature storage (which would allow pathogen growth) into a benefit by using photochemical inactivation. The amotosalen-UVA treatment creates a stable product that can be stored at room temperature without risk of pathogen proliferation, turning a potential hazard into an advantage for extended usability
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution extends the usable duration of cryoprecipitate beyond current guidelines, reducing waste and increasing efficiency by allowing storage for up to 168 hours post-thaw, while ensuring pathogen inactivation and consistent fibrinogen levels.
Implementation Method 1
treating plasma with amotosalen and UVA light
Implementation Method 2
slow, controlled thawing of frozen plasma (e.g., whole blood-derived fresh frozen plasma, or FFP), for example between 1° and 6° C (e.g., 4 ± 2° C), which results in the formation of a white precipitate
Implementation Method 3
recovering the precipitate following separation from the liquid plasma portion, also referred to herein as 'supernatant,' such as by refrigerated centrifugation
Data Source
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AI summary
Provided herein are compositions and kits including a pathogen-inactivated cryoprecipitate suitable for infusion into a subject at least 1 day after thawing. The methods are useful in the efficient preparation of cryoprecipitates with desirable characteristics, including pathogen-inactivated cryoprecipitates that are suitable for infusion into a subject at least 1 day after thawing.