Journal Article

Investigating a Signal of Acquired Haemophilia Associated with COVID-19 Vaccination: A Systematic Case Review

Cappello, E, Valdiserra, G, Focosi, D, Tuccori, M, Franchini, M, Moretti, U, Bonaso, M

2022

Overview

Introduction: Acquired haemophilia A (AHA) is a rare, haematological disorder characterized by the development of autoantibodies to Anti-Factor VIII (FVIII), which can cause spontaneous hemorrhage 1. During 2021, some authors reported an unusual and unexpected number of AHA diagnoses that were temporally related to COVID-19 vaccination2,3 Objective: To explore a possible signal of risk of AHA associated with COVID-19 immunization. Methods: We performed a disproportionality analysis on the World Health Organization (WHO) database (VigiBase) to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. We calculated the information component (IC) for all the COVID-19 vaccines and for single COVID-19 vaccine product using the entire database as reference. Reports of AHA have been systematically reviewed all the selected cases to check for clinical plausibility Results: In Vigibase, we identified 150 cases of suspected AHA associated with COVID-19 vaccines (146 included the PT \"acquired haemophilia\"). Only three vaccine products have been reported as suspected causative agents for AHA. The disproportionality analysis showed a significant IC for the Preferred term \"Acquired haemophilia\" associated with all COVID-19 vaccines (IC: 1.3; IC025: 1.1) and with the vaccine product BNT162b2 (IC: 1.9; IC025: 1.6). After the integration with data available on VAERS and on the medical literature, and after the elimination of duplicates, 96 unique cases of AHA following COVID-19 vaccines (mostly mRNA vaccines) have been reviewed. Overall, about 22% of cases occurred in patients B 65 and no case associated with pregnancy was reported. Patients with at least one pre-existing condition that can be considered a risk factor for AHA (history of AHA, cancer, autoimmune disorder) were 20 (21%). A pre-existing condition predisposing to AHA was excluded in 57 (59%) of cases and not reported in 19 (20%) cases. The outcome was death in 10 (11%) patients and complete resolution or recovering in 39 (41%) patients with a single resolution without specific AHA treatment. Median time from last vaccine dose to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Conclusion: Our disproportionality analysis confirmed a reporting risk for AHA associated with COVID-19 vaccines. The case review analysis identified several good-quality reports of AHA for which no alternative causes other than COVID-19 immunization can be considered. Although detection bias should be considered to explain the unexpected frequency of AHA in the population, the signal identified is robust and deserves further investigation.

• Publisher: Springer Nature B.V
• Subject: Autoantibodies / Autoimmune diseases / Coagulation factors / Coronaviruses / COVID-19 vaccines / Hematological diseases / Hemophilia / Hemorrhage / Immunization / mRNA / Patients / Pre-existing conditions / Risk analysis / Risk factors / Severe acute respiratory syndrome coronavirus 2 / Vaccines