Hemophilia A is caused by mutations in the F8 gene that codes for coagulation factor VIII (FVIII), also called antihemophilic factor. The presence of variants in the F8 gene leads to low concentrations of FVIII in the blood, resulting in a reduced ability of the blood to clot and an increased risk of both injury-induced and spontaneous bleeding and joint damage.
As it is an X-linked disease, females are generally carriers of the disease, while males are more likely to express and suffer from the disease because they have only one X chromosome. In affected families, males who develop the disease inherit a copy of the mutated F8 gene from their carrier mothers. For a woman to have hemophilia, both X chromosomes must be affected.
The prevalence of hemophilia A is estimated to be about 1 in 6,000 male individuals.
The symptoms of hemophilia A and B are similar and include an increased risk of bleeding after injury or even spontaneously. Bleeding can also occur at the joint level causing damage to joint tissue, known as hemophilic arthropathy. The risk of arthropathy increases with age and it usually affects the same joints recurrently.
Hemophilia A increases predisposition to cardiovascular disease and may have an impact on brain function, due to possible cerebral hemorrhagic events.
The severity of symptoms depends on the remaining FVIII levels and three types are distinguished:
- Severe: clotting factor VIII level is less than 1 international unit [IU]/dL (<1% of normal). It manifests in the first years of life due to spontaneous bleeding or after minor injuries.
- Moderate: clotting factor VIII level is 1-5 IU/dL (1-5% of normal). It is usually detected in childhood when minor trauma occurs.
- Mild hemophilia: clotting factor VIII level is 5-40 IU/dL (5-40% of normal). It is usually detected before or after surgery.
Between 50-60% of patients with hemophilia have moderate or mild hemophilia.
The most common prophylactic treatment of patients with severe hemophilia is regular replacement therapy with CFCs (clotting factor concentrates) that helps to maintain joint health and reduce the frequency of bleeding.
In recent years, new strategies have been developed, such as monoclonal antibody therapy aimed at restoring clotting factor VIII function and gene therapy. Emicizumab (Hemlibra®) is a drug containing monoclonal antibodies approved by both the FDA (US Food and Drug Administration) and the EMA (European Medicines Agency) for the treatment of hemophilia A. This drug significantly reduces the risk of bleeding in children and adults and improves the quality of life of hemophilia A patients.
Today, the life expectancy of hemophilia A patients is high due to remarkable advances in genetics and medicine. With proper treatment, patients can lead a nearly normal life.