Risk of Developing Inhibitors in People with Milder Forms of Hemophilia

Specifics of Treatment for Milder Hemophilia Patients

Hemophilia A is an inherited, X-linked bleeding disorder characterized by reduced or absent production of clotting factor VIII (FVIII). Unlike severe hemophiliacs, who tend to bleed often without clear cause and for whom regular FVIII concentrate administration is standard care, patients with milder forms of hemophilia receive substitution therapy only in cases of injury or surgery.

The development of neutralizing antibodies, known as inhibitors, is a serious complication primarily in the treatment of severe hemophilia A — affecting up to a third of severe hemophiliacs, especially during the initial doses of FVIII concentrate. In milder hemophilia, it is a rare but still significant complication with a lifelong risk of development. It is crucial to attempt to prevent this treatment complication and to be aware of the associated risks.

INSIGHT Study

As one of the largest studies focusing on non-severe hemophilia patients, INSIGHT provided data on mild and moderate hemophiliacs (baseline FVIII levels of 2–40%) and their risk of inhibitor development. Of the total 2,709 patients, those with inhibitors (cases; n = 75) and matching controls without inhibitors (n = 223) were selected. The study found that peak treatment moments (5 or 10 consecutive days of FVIII concentrate administration) did not significantly increase the risk of inhibitor development. Conversely, FVIII concentrate use during surgery or high average doses (>45 IU/kg in a single exposure day) increased this risk (adjusted odds ratios [aOR] 4.2 and 7.5).

Conclusion

For milder hemophilia patients, it is crucial for the healthcare staff to carefully decide not only when to administer FVIII concentrate but also in what intensity to administer it to patients without severe forms of the disease. This is particularly important during elective procedures and in the context of doses applied during surgeries. Preventing the development of inhibitors as a serious complication can significantly impact the patient's quality of life.

(eza)

Source:

van Velzen A. S., Eckhardt C. L., Peters M. et al., Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study. J Thromb Haemost 2017; 15(7): 1422−1429, doi: 10.1111/jth.13711.