Drug-associated acquired hemophilia A: an analysis based on 185 cases from the WHO pharmacovigilance database

Introduction Acquired hemophilia A (AHA) is a rare autoimmune hemorrhagic disease occurring in several underlying conditions. Drug-associated AHA (D-AHA) is poorly addressed nowadays. Aim This work aims to identify and characterize which drugs are associated with AHA using the WHO global database of reported potential effects of medicinal products (VigiBase). Methods First, we realized a disproportionality analysis using the information component (IC) to identify D-AHA in VigiBase. IC compares observed- and expected-values in order to find associations between drugs and adverse drug reactions (ADRs) using disproportionate Bayesian reporting. IC025 is the lower end of a 95% credibility interval for the IC. Then, we collected cases of drugs significantly associated with AHA from July 2004 to November 2021. Results 14 drugs with IC025 > 0 were identified representing a total of 185 cases. D-AHA occurred more frequently in men (59%) than women (41%). The median (min-max) age at onset was 75 years (8-98). The median [Q1-Q3] time to onset of D-AHA from the start of the suspected drug was 30 days [9.5-73.75] and 10% of cases resulted in a fatality. The drugs associated with the highest IC025 (IC025 > 2) were Clopidogrel, Alemtuzumab, Omalizumab. This study retrieved for the first time three usually used drugs (3/14) that exhibit a significant pharmacovigilance signal for D-AHA. Conclusion This worldwide pharmaco-epidemiologic study updates the list of the drugs associated with AHA. The clinician should be aware of these possible severe ADR, which might require larger epidemiological and pathophysiologic studies.