Haemophilia A is a genetic disease caused by the presence of mutations affecting the factor VIII gene. However, in some cases, even people who do not present any mutations can be affected by this disease. These individuals have a rare form of haemophilia A of autoimmune origin, known as Acquired Haemophilia A (AHA). In patients with this form of haemophilia, factor VIII is produced normally but, at some point in their life, the immune system suddenly starts to produce antibodies, called “inhibitors”, against factor VIII. The inhibitors produced by individuals with AHA act by attacking factor VIII and neutralising its effect, in a very similar way to that experienced by patients with congenital haemophilia A. In the case of AHA, however, the inhibitors do not attack factor VIII originating from the exterior and administered by infusion, but that produced by the body itself, which is why we speak of autoimmunity.
Who and when does AHA strike?
AHA mainly affects elderly patients, on average those between 64 and 78 years of age, although it can also occur in younger patients, especially in the case of pregnancy or autoimmune disease. The reasons for the onset of AHA have not yet been clarified, but it is assumed that certain genetic and environmental risk factors are involved.
Diagnosis and treatment
Because of its high risk of mortality, it is essential that AHA is diagnosed as soon as possible and adequately treated with a therapeutic strategy that relies primarily on the use of haemostatic agents, i.e. drugs that promote blood clotting and stop bleeding, together with immunosuppressive drugs, usually corticosteroids and cyclophosphamide, which soothe the immune system and eradicate inhibitors. In AHA, the use of factor VIII as replacement therapy is only effective when the concentration of inhibitors produced is particularly low, i.e. with a titre below 5 BU (Bethesda Units). In these cases, the few inhibitors present in the blood are not sufficient to neutralise the large quantities of Factor VIII infused, which can act undisturbed and allow normal blood clotting. In the case of high-titre inhibitors, on the other hand, the only treatments that are effective in stopping bleeding until immunotolerance is restored are haemostatic drugs and bypassing agents, i.e. molecules that allow the clotting process to be completed even in the absence of factor VIII.
Despite being an insidious condition, AHA can be defeated by a timely diagnosis and the support of a specialist doctor who is able to administer effective, albeit complex, therapy. Once the inhibitors have completely disappeared, the patient can be considered cured and does not require further treatment, only routine monitoring.
Kruse-Jarres R. et al. Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol., 2017. 92:695–705.