Acquired Hemophilia A Treatment Gaps Identified

Acquired hemophilia A (AHA) is an exceptionally rare autoimmune disorder characterized by the development of autoantibodies against coagulation factor VIII (FVIII), known as inhibitors. These inhibitors impede FVIII activity, disrupt the coagulation cascade, and impair hemostasis, leading to severe bleeding diatheses. Additionally, these manifestations can include soft tissue hematomas, mucosal bleeding, and life-threatening bleeding within vital organs, occurring spontaneously or after minor trauma or medical procedures.

AHA is estimated to affect around one in a million people annually, but this might be an underestimation due to undiagnosed cases. A lack of clinical suspicion often delays diagnosis, resulting in mortality rates ranging from 9% to 33%.

“The estimated incidence of AHA is approximately one case per million per year, which may be an underestimation owing to undiagnosed cases,” said researchers. “Given the rarity of this condition, a lack of clinical suspicion can delay diagnosis, resulting in mortality rates of 9-33%.”

Unlike congenital hemophilia A, which primarily affects males and is inherited, AHA is not inherited and affects both males and females equally. The incidence of AHA increases with age, particularly in elderly patients, with a median age at diagnosis of 73.9 years. There's also a peak in women during childbearing age, typically during the peripartum period. Approximately half of AHA cases are associated with other medical conditions, such as autoimmune diseases, malignancies, or drug use, while the other half is idiopathic.

One critical difference between AHA and congenital hemophilia A is the pharmacokinetics of inhibitors. In congenital hemophilia A, inhibitors exhibit type 1 kinetics, neutralizing FVIII at a linear rate proportional to the inhibitor concentration. AHA inhibitors, on the other hand, exhibit type 2 non-linear pharmacokinetics. This means they have a rapid inactivation phase followed by a slower equilibrium phase. During the equilibrium phase, inhibitors often cannot completely inhibit FVIII, leading to residual FVIII activity. This characteristic can lead to misdiagnosis and inappropriate treatment, emphasizing the importance of understanding type 2 pharmacokinetics for effective clinical management.

To investigate the state of AHA treatment and management, a search was conducted with specific terms and criteria, including articles in English published between January 2016 and November 2021. The aim was to cover the period during which recommended first-line hemostatic options for AHA were available in the United States.

Of the 98 authors of these articles, 18 specialties were represented, with internal medicine being the most common. The patient characteristics and management histories were described in detail. Unfortunately, 17 of the 24 articles did not mention consultation with a hemophilia expert. Moreover, 15 of the 24 studies did not reference the 2009 international AHA recommendations, and 12 of them did not discuss all recommended first-line hemostatic treatment options. In a subset of articles published after the 2017 AHA guidance was released, eight out of 17 did not cite them, and five of those eight also did not discuss all the available recommended first-line hemostatic treatment options. Three articles published in 2021 did not reference the 2020 international AHA recommendations. This information suggests a significant lack of adherence to best practices and guidelines for AHA treatment.

Furthermore, 12 cases seemed to be associated with a delayed diagnosis, which is a critical issue in AHA management.

In conclusion, this study has revealed variability in hemostatic management by non-hemophilia experts in the United States. It also highlights potential barriers to AHA diagnosis and treatment, suggesting that more resources and awareness are needed to improve clinical outcomes for these patients.

Non-hemophilia experts are urged to consult with specialists experienced in treating AHA, follow the most recent AHA guidelines, and work to increase awareness of this rare condition. Improved management and diagnosis of AHA are essential to reduce mortality rates and enhance the quality of life for affected individuals.

“Our findings indicate variability in hemostatic management by non-hemophilia experts in the United States,” concluded researchers.

“[I]t is apparent that more efforts to help raise the level of awareness of AHA among non-hemophilia experts in the United States are urgently needed to improve clinical outcomes for these patients.”

Reference:

Sharathkumar A, Mokdad AG. Review of Potential Barriers to Effective Hemostatic Management of Acquired Hemophilia A by Non-Hemophilia Experts in the United States. Cureus. 2023;15(1):e33927. Published 2023 Jan 18. doi:10.7759/cureus.33927