OA1-AM24-MN-14 - Aggregates in Cold Stored Platelet Units have Diverse Phenotypes that are Removed by Transfusion Filters

The FDA Guidance “Alternative Procedures for the Manufacture of Cold-Stored Platelets (CSP) Intended for the Treatment of Active Bleeding when Conventional Platelets Are Not Available or Their Use Is Not Practical” permits the storage of apheresis platelets at 1-6°C for up to 14 days, when such platelets are intended for the treatment of active bleeding and when conventional platelets are not available or their use is not practical. In support of these efforts Vitalant started a pilot to manufacture CSPs.

Study

Design/Methods:

Apheresis platelets in 100% plasma (Trima, Terumo BCT) were moved into cold storage within 4 hrs of collection. CSPs with aggregates were returned from hospitals, photographed, scored for aggregate phenotype, and tested for platelet concentration, pH, metabolism (glucose, lactate), and activation (flow cytometry for P-selectin, Lactadherin, CD63, CD41/61 complex) parameters. Units were cold stored until expiration and then passed through a bedside transfusion filter (170-260mm). Samples were taken during storage and on day 14 pre- and post-filtration.

Results/Findings:

Aggregated units represent 8-9% of released CSPs. During the study period, a total of 46 aggregated units were returned on average on day 9 of storage (range 2-14 days). Small aggregates were the predominant phenotype observed in 51% of units. Phenotypes did not change over storage and ranged from small-grainy to large shavings/sheets. Day 0 platelet counts were 1354±252x10³/mL. A drop in platelet count occurred early after refrigeration with small decreases continuing over storage (Table 1). The drop in platelet count in non-aggregated CSP was less pronounced at 14%, compared to 45% in aggregated units. Trends with Lactadherin and P-selectin (increase), CD63 and CD41/61 complex (decrease), and slower metabolism were observed. Transfusion filter sizes were 170, 180 and a range of 170-260 mm. Filtration removed aggregates from all CSP units, except for one unit with large shaving/sheet aggregates, with small grainy aggregates remaining post-filtration that persisted for 24 hrs (filter 170-260um). Mean post filtration platelet recovery was 94±26%. There were 4 repeat donors with two of the donors having the same aggregate phenotype for both donations, and one donor presented with the same aggregate phenotype for 2 out of 3 collections.

Conclusions:

Aggregates in CSP were successfully removed by filtration regardless of size, and post-filter platelet recovery remained high. Filtration significantly decrease markers of CSP activation supporting a hypothesis that activated CSPs are removed concurrently with aggregates. Pre- and post-filter hemostatic function was not tested in this study and warrants further investigation. No distinct predictors for formation of large versus small aggregates were identified.