OBJECTIVES: Febrile Non-Hemolytic Transfusion Reactions (FNHTR) are acute events that may result in hospitalization. The study assessed FNHTR occurrence and potential risk factors among Fee-for-Service U.S. Medicare beneficiaries aged 65+ transfused in the institutional outpatient setting.

METHODS: Our retrospective claims-based study used Medicare data for 2016-2022. Procedure and revenue center codes identified transfusions, whereas diagnosis codes ascertained FNHTR recorded within one day of outpatient transfusion visits. We evaluated unadjusted FNHTR rates and 95% confidence intervals per 100,000 transfusion visits: overall, by year, immunocompromised (IC) status, recipient and transfusion characteristics.

RESULTS: Of 2,991,851 outpatient transfusion visits, 526 had a recorded FNHTR diagnosis, a rate of 17.6 per 100,000 (95% CI 16.1-19.1). Pre- (2016-2019) vs. during COVID-19 pandemic (2020-2022), FNHTR rates were 22.0 (19.9-24.3) vs. 11.0 (9.3-13.0). The rates by number of units ranged from 14.6 (12.7-16.8) for 1 unit to 29.6 (14.1-62.1) for ≥5 units. Rates were 23.6 (21.4-26.2) vs. 10.9 (9.3-12.8) for males and females, 20.3 (18.5-22.3) vs. 10.1 (8.1-12.6) for IC and non-IC, and 19.4 (17.7-21.3) vs. 11.8 (9.5-14.6) with and without six-month transfusion history. Rates by blood components were: plasma only [5.7 (1.4-22.7)], RBCs only [10.1 (8.9-11.5)], platelets only [26.8 (22.2-32.3)], and multi-component transfusions [83.2 (71.9-96.3)] mostly comprised of RBCs and platelets. The highest rates by component processing included: whole-blood-derived platelets only [42.5 (22.1-81.7)], pathogen-reduced platelets only [48.7 (33.9-70.1)], and non-irradiated non-leukoreduced platelets only [84.7 (21.2-338.0)].

CONCLUSIONS: Our 7-year population-based investigation identified significantly lower FNHTR rates during the COVID-19 pandemic. The study found substantially higher FNHTR rates for platelet transfusions, males, IC beneficiaries, with greater units transfused, and history of transfusion(s), which are likely related to reaction mechanisms (e.g., prior alloimmunization, pro-inflammatory mediators). Pathogen-reduced platelet transfusions had a higher rate of FNHTR, which needs further investigation. The study highlights the utility of Medicare databases in detecting rare transfusion events.