(P-TS-3) A Pragmatic Experience Validating Production of Cold Stored Platelets

There has been renewed interest in cold stored platelets (CSP) for actively bleeding patients due to improved storage time and potential for superior hemostatic properties. In June 2023 the United States Food and Drug Administration (FDA) released a guidance for industry regarding the manufacture of CSP. Production in 100% plasma or platelet additive solution (PAS) are both acceptable and agitation is optional. However, storage in plasma is associated with aggregate formation in CSP. Our blood center currently produces conventional apheresis platelets collected via the Trima Accel system (Terumo, Somerset, NJ), leukocyte-reduced, suspended in 100% plasma and treated with pathogen reduction technology (PRT) (Intercept, Cerus, Concord, CA). We performed an internal validation to determine if cold storage would meet FDA requirements for platelet count and pH, and Transfusion Services (TS) thresholds for aggregates.

Study

Design/Methods:

Apheresis derived platelets were collected and PRT treated per manufacturer instruction, then placed in cold storage at 1 to 6°C within 4 hours after completion of PRT. 4 cohorts of storage conditions at TS were tested:

1) Agitation on day 14

2) Agitation on days 10 and 14

3) Agitation on days 5, 10, 14

4) Agitation every 2 days

All units were returned to SBC on day 14 for pH and count tests. The threshold for aggregates determined unacceptable for transfusion was >10 measuring < 3mm or any aggregates >3mm.

Results/Findings:

100% of CSP units formed a sediment of platelets during storage. This was successfully re-suspended into solution with manual agitation. However, on subsequent days of assessment, they formed aggregates in excess of the transfusable threshold; that could not be resolved (Figure 1). In cohort 1, 55% of units were not transfusable on day 14. In cohort 2, 67% of units were not transfusable on day 14. In cohort 3, 67% and 89% of units were not transfusable by days 10 and 14 respectively. 100% of the units in cohort 4 were not transfusable on day 10 and 14. All units met FDA pH and count requirements on day 14 when returned to the blood center for quality control testing.

Conclusions:

CSP have the potential to reduce waste and variability in supply. However, production methods and storage conditions may create barriers to implementation that are not currently addressed by the FDA guidance. CSP produced and stored in the conditions we describe may lead to increased waste. Handling events such as issue and return of unused platelets might stimulate an unacceptable level of aggregate formation. Various factors such as PAS, citrate concentration, and agitation have been shown to influence aggregate formation, and further guidance will be beneficial if blood centers, and transfusion services are to successfully implement CSP.