Paolo Rebulla

Background: Characterization of platelet gel (PG) from different blood sources and preparation methods remains incomplete. Study Design and Methods: This study compared the weight, growth factor (GF) content, and gelation dynamics (via rotational thromboelastometry, ROTEM) of allogeneic PG prepared from adult blood (AB) and cord blood (CB) platelet concentrates (PC). ABPC were suspended in 100% plasma or 35% plasma/65% platelet additive solution (PAS), while CBPC were suspended in 100% plasma. PG was prepared in commercial BioNest D mini‐bags using a method with calcium gluconate, locally made cryoprecipitate, and thrombin (CT), or a reference method with calcium gluconate and commercial batroxobin (BA). PG was analyzed at 30 min and 6 h. Results: At 30 min, PG weights were higher with CT than BA across all conditions. With 5 mL ABPC in 100% plasma, weights were 7.20 ± 1.07 g (CT) versus 2.72 ± 0.19 g (BA); with 10 mL ABPC in PAS, 9.49 ± 2.86 g (CT) versus 3.87 ± 3.1 g (BA); and with 4.09 ± 0.45 mL CBPC, 5.62 ± 1.21 g (CT) versus 2.04 ± 0.78 g (BA). All PGs lost mass by 6 h, but CT consistently retained more weight. GF percent retention in the PG at 6 h was higher with CT. ROTEM results showed differences in clotting time and comparable values of maximum clot firmness between PG from AB and CB. Discussion: The CT method is a promising alternative for producing allogeneic PG using affordable, locally sourced reagents.

The development of pathogen reduction technologies (PRT) for labile blood components is a long-pursued goal in transfusion medicine. While PRT for red blood cells and whole blood are still in an early phase of development, different PRT platforms for plasma and platelets are commercially available and routinely used in several countries. This review describes complementary strategies recommended by the US FDA to mitigate the risk of septic reactions in platelet recipients, including PRT and large-volume delayed sampling, and summarizes the main findings of recent reports discussing economical and organizational issues of platelet PRT implementation. Sophisticated mathematical analytical models are available to determine the impact of PRT on platelet costs, shortages and outdates in different settings. PRT implementation requires careful planning to ensure the availability of sufficient economical, technological and human resources. A phased approach was used in most PRT implementation programs, starting with adult and pediatric immunocompromised patients at higher risk of developing septic platelet transfusion reactions. Overall, the reviewed studies show that significant progress has been made in this area, although additional efforts will be necessary to reduce the storage lesion of PRT platelets and to expand the sustainable applicability of PRT to all labile blood components.

Most public cord blood banking programs are currently facing financial difficulties due to a progressive decline in the number of cord blood transplants performed worldwide and to a high discard rate of the donated units caused by progressively increasing thresholds of the stem cell dose required to perform safe and effective hemopoietic cord blood transplants. Recycling a proportion of unused cord blood units to prepare novel cord blood components obtained with minimal manipulation (platelets, plasma, red blood cells) and to develop more technologically complex products regulated in the US as Cellular and Gene Therapy Products and in Europe as Advanced Therapy Medicinal Products [e.g. virus-specific T cells (VST), natural killer (NK) cells, induced pluripotent stem cells (iPSCs) is a promising strategy to increase the therapeutic value and reduce the financial deficits of public cord blood banking. Based on encouraging preliminary evidences reported in the literature, additional laboratory studies, large multicenter clinical trials and international regulatory harmonization are necessary to achieve these important goals. This article describes organizational, methodological and regulatory advancements developed in Italy and Spain to promote the clinical use of cord blood platelets, plasma and red blood cells.

Platelet transfusion therapy: hot topics in 2021 Paolo Rebulla

Summary: Pathogen reduction technologies (PRTs) have been developed to further reduce the current very low risks of acquiring transfusion‐transmitted infections and promptly respond to emerging infectious threats. An entire portfolio of PRTs suitable for all blood components is not available, but the field is steadily progressing. While PRTs for plasma have been used for many years, PRTs for platelets, red blood cells (RBC) and whole blood (WB) were developed more slowly, due to difficulties in preserving cell functions during storage. Two commercial platelet PRTs use ultra violet (UV) A and UVB light in the presence of amotosalen or riboflavin to inactivate pathogens’ nucleic acids, while a third experimental PRT uses UVC light only. Two PRTs for WB and RBC have been tested in experimental clinical trials with storage limited to 21 or 35 days, due to unacceptably high RBC storage lesion beyond these time limits. This review summarizes pre‐clinical investigations and selected outcomes from clinical trials using the above PRTs. Further studies are warranted to decrease cell storage lesions after PRT treatment and to test PRTs in different medical and surgical conditions. Affordability remains a major administrative obstacle to PRT use, particularly so in geographical regions with higher risks of transfusion‐transmissible infections.

BACKGROUND: Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen‐reduction technologies versus standard platelets.STUDY DESIGN AND METHODS: The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention‐to‐treat analysis was conducted on 424 evaluable patients.RESULTS: In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one‐sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one‐sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%‐74%; Intercept) and 34% higher (95% confidence interval, 16%‐54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%‐39%; Intercept) and 32% higher (95% confidence interval, 10%‐57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients.CONCLUSION: Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen‐reduced platelets treated with two commercial pathogen‐reduction technologies.