Cases of acquired hemophilia A following COVID‐19 vaccines: Cogent safety signal or possible reporting/detection bias? Preliminary evidence from Tuscany, Italy

Abstract

AbstractPurposeSeveral case reports of acquired hemophilia A (AHA) following COVID‐19 vaccines were recently published. A possible increased incidence of AHA during the COVID‐19 vaccination campaign was also suggested. We aimed at generating evidence for the preliminary assessment of the association between AHA and COVID‐19 vaccination through an ecological study in one Italian region, Tuscany.MethodsAn ecological study was performed using the population‐based administrative data source of Tuscany. Per each year between 2017 and 2021, we included patients aged 5+ and active into the database as of January 1. Temporal patterns of annual incidence of possible AHA cases and AHA‐tested patients were respectively observed. The rates of possible AHA cases per AHA‐tested patients were calculated in 2021 and 2017–2019, respectively (calendar year 2020 was excluded because non‐representative of the pre‐pandemic era). Age–sex standardization was applied. Poisson's 95% confidence intervals (95% CI) were estimated. Statically significant differences were defined as absence of 95% CI overlap.ResultsIn 2021, standardized incidence of both possible AHA cases (5.6/million subjects/year; 95% CI = 3.4–8.7) and AHA‐tested patients (60.7/1000 subjects/year; 95% CI = 60.4–60.9) showed the lowest point estimates, though only the latter was statistically different compared to previous calendar years. The standardized rate of possible AHA cases per AHA‐tested patients was 9.2/100000 (95% CI = 5.6–14.3) in 2021 and 12.5/100000 (95% CI = 8.2–18.1) during 2017–2019.ConclusionsThese preliminary findings do not support the hypothesis of an increased incidence of AHA cases during the COVID‐19 vaccination campaign. However, in 2021, the still ongoing healthcare access restrictions might have contributed to the low incidence of AHA and laboratory tests observed. Therefore, large‐scale multi‐database studies are warranted.