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Semin Thromb Hemost 2023; 49(01): 015-026
DOI: 10.1055/s-0042-1754389
Review Article

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

Massimo Franchini
1   Division of Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
,
Emiliano Cappello
2   Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
,
Giulia Valdiserra
2   Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
,
Marco Bonaso
2   Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
,
Ugo Moretti
3   Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
,
Daniele Focosi
4   North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy
,
Marco Tuccori
2   Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
5   Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy
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Abstract

Acquired hemophilia A (AHA), a rare but life-threatening disorder, most commonly occurs in older people and during pregnancy. During the coronavirus disease 2019 (COVID-19) vaccination campaign, an unexpected number of newly diagnosed AHA patients have been identified in clinical practice that were temporally related to COVID-19 vaccination. We present the result of a signal detection analysis aimed at exploring a possible association between COVID-19 immunization and occurrence of AHA. A disproportionality analysis on the World Health Organization (WHO) database was performed to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. Reports of AHA associated with any COVID-19 vaccine included in the WHO database were then integrated with those available on the Food and Drug Administration Vaccine Adverse Events Reporting System and those published in the medical literature. The WHO database included 146 reports of AHA. The information component (IC) was significant for the association of AHA with all COVID-19 vaccines (IC025: 1.1) and with the vaccine product BNT162b2 (IC025: 1.6). After duplicate exclusion, 96 unique cases of AHA following COVID-19 vaccines have been reviewed. Median time to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Overall, in 57% of the investigated cases, a preexisting condition predisposing to AHA was excluded. About 22% of cases occurred in subjects with age ≤65 years and there was no case associated with pregnancy. Mortality was 11%. Although we cannot exclude that the unexpected frequency of AHA diagnosis can be explained by a detection bias, the signal for COVID-19 vaccine-related AHA is robust and deserves further investigations.

Keywords

acquired haemophilia A autoimmunity - COVID-19 - mRNA vaccines - BNT162b2 - mRNA-1273

Author Contributions

M.F., M.T., and D.F. conceived and developed the presented idea. M.F. and D.F. wrote the first draft. U.M. curated [Table 1]. E.C., G.V., and M.B. curated [Fig. 1], [Tables 2]–[4], and supplementary data. M.T. wrote the paper with input from all the authors.


Supplementary Material



Publication History

Article published online:
02 September 2022

© 2022. Thieme. All rights reserved.

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