Platelets have the greatest risk of causing septic transfusion reactions due to their room temperature storage requirements. Numerous strategies have been implemented over the years to mitigate this risk including in-line sample diversion, large volume-delayed sampling, and automated testing platforms. While these developments have decreased the rate of septic transfusions, the risk remains.
In an effort to reduce this risk, the FDA released a guidance on strategies for bacterial mitigation in the collection and transfusion of platelets that went into effect on October 1, 2021. The guidance delineates several options including pathogen reduction technology (PRT), culture-based methods, and rapid testing. The 2021 AABB Platelet Survey showed that 62% of responding hospitals selected pathogen-reduced platelets (PR PLT) as their preference for meeting FDA guidelines, and this is expected to increase.
The INTERCEPT ® system by Cerus is currently the only FDA-approved PRT. INTERCEPT ® utilizes Amotosalen which docks between nucleic acids, then crosslinks when exposed to UVA, inhibiting replication of a variety of bacteria, viruses, spirochetes, protozoa, and human leukocytes. Amotosalen is a derivative of psoralens – UV-sensitive, naturally occurring compounds with antibiotic activity found in celery and citrus fruits. One concern among the medical community is about the safety of PR PLT for neonates and pediatric patients. Several studies have demonstrated that PR PLT are clinically equivalent to conventionally manufactured apheresis platelets (CONV PLT), but adult data cannot be reliably extrapolated to children and infants, and existing data on the use of PR PLT in this population are limited.
A retrospective review of platelet transfusions to pediatric and neonatal patients (<18 years) was conducted at the University of California, Los Angeles (UCLA) over a 300-day period in 2017. The neonatal cohort included patients in the low and very low birth weight categories. The hospital blood bank maintained a dual inventory of PR and CONV PLT that were distributed based on availability. Platelet transfusions were stratified by age and diagnosis most relevant to the transfusion. Transfusion reactions were obtained from both reports to the blood bank, as well as review of patients’ pre- and post-transfusion blood cultures when available.
A total of 191 patients received 1,010 platelet transfusions from 892 distinct units (506 PR, 386 CONV) averaging 5.3 transfusions per patient. Overall, 66.7% of the platelets were transfused to patients with hematologic malignancies. Of these patients, those undergoing hematopoietic stem cell transplant received of the largest number of transfusions per patient (24.9) relative to other diagnostic categories. Because the platelets were issued randomly and based on availability, these patients were also most likely to receive a combination of PR and CONV PLT, thus the data were not informative regarding potential differences in platelet usage between the two platelet products.
Cardiac surgery was the most common diagnosis (38% of patients) requiring platelet transfusions. These patients also received the fewest units per patient (1.5) and were therefore most likely to receive only one type of platelet product. Of these and all patients receiving only one type of platelet, the average usage was 1.8 transfusions and 1.3 units/patient for PR PLT vs 1.6 transfusions and 1.4 units/patient for CONV PLT. These differences were not statistically significant.
Review of adverse outcomes demonstrated no reports of bacterial contamination from either PR or CONV PLT. Four patients experienced a total of 7 acute transfusion reactions: one episode of circulatory overload, 3 mild allergic reactions and 3 moderate-to-severe allergic reactions. These were seen in response to both PR and CONV PLT, with no statistically significant differences.
Because psoralens are UV-sensitive and can increase skin sensitivity in patients, concerns have been raised regarding concurrent use in neonates undergoing phototherapy. FDA-approved phototherapy instruments emit light in the 430-490 nm range, while Amotosalen absorbs in the 320-400 nm range. Despite no expected reaction, neonates undergoing phototherapy who also received PR PLT were evaluated for rash. There were no reports of rash in these 13 patients.
The limitations of this study include a small patient cohort and a short study period. The rates of acute transfusion reactions are consistent with reported rates in adults in pediatric patients. The observed low rate of acute reactions aids in the adoption of PR PLT. While advances in bacterial mitigation have significantly improved the rates of septic transfusion reactions, continued vigilance is of utmost priority to ensure the safety of patients requiring transfusion, particularly in this vulnerable patient cohort. Long-term follow-up for pediatric patients, particularly neonatal and chronically transfused patients, is a necessary addition to currently available data.
Baia Lasky, MD
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