Background: A signal of a rare bleeding disorder detected after vaccination

An analysis of 27 spontaneous reports in the French pharmacovigilance database supports a potential safety signal for acquired hemophilia A (AHA) after vaccination with the COVID-19 mRNA vaccine tozinameran. The findings do not establish a causal relationship between vaccination and the onset of the disorder.

AHA is a rare autoimmune bleeding disorder reported in association with autoimmune diseases, malignancies, infections, pregnancy, and certain drugs. Cases of AHA arising after COVID-19 vaccination have also been published. In France, a potential AHA signal was detected in April 2021 during real-time monitoring of adverse reactions to tozinameran (BNT162b2; Comirnaty, Pfizer-BioNTech).

To examine this signal, the researchers conducted pharmacological and medical analyses of spontaneous reports of AHA after vaccination registered in the French Pharmacovigilance Database (FPVD). This should be distinguished from a study that follows all vaccine recipients to measure incidence.

Key findings: Median time to onset of 23 days; worsening after re-exposure in two patients

The analysis included 27 reports. AHA occurred mainly after the second dose, and the median time to symptom onset was 23 days. This does not mean that the mean was 23 days or that every patient developed the disorder within 23 days. The abstract does not provide the full distribution of onset times or detailed criteria for calculating the interval.

The most common symptom was spontaneous hematoma. Nineteen cases were reported in which the bleeding syndrome was assessed as severe and accompanied by anemia. Seventeen patients received treatment for bleeding, and 23 received corticosteroids alone or in combination with immunosuppressants. The abstract alone does not, however, allow comparison of the effects of individual drugs or outcomes by treatment.

Mortality among the reported cases analyzed was 15%. This figure should not be interpreted as the risk of death among all vaccine recipients. The abstract provides no information broken down by cause of death or data with which to determine whether the vaccine contributed to the deaths.

The researchers stated that, despite thorough investigation, they could not identify another cause of AHA in many cases. Symptoms worsened in two patients after re-exposure to tozinameran. Worsening after re-exposure is an observation to consider when assessing a potential association, but this finding alone does not establish an autoimmune mechanism specific to a vaccine component or a causal relationship.

Implications and outlook: Distinguishing a safety signal from the risk of developing the disorder

The researchers said the analysis supports a potential AHA signal associated with tozinameran and emphasized awareness among healthcare professionals. The findings may serve as a reference when evaluating bleeding cases after vaccination. The observation that no other cause was identified is also relevant to that assessment, but it does not directly establish that the vaccine was the cause.

The provided abstract does not report the total number of vaccine recipients, a control group, or an incidence comparison with unvaccinated people. These data therefore cannot be used to calculate the incidence or excess risk of AHA after vaccination. The distribution of patients by age or underlying condition, as well as their long-term course, is also unavailable. It is therefore difficult to extend these findings into evidence for identifying a specific high-risk group or assessing the effects of individual vaccination plans.

This study is an analysis of spontaneous reports published in the journal Haemophilia. This article was prepared within the scope of information available in the provided study abstract and bibliographic record.