What is hemophilia?

What is Hemophilia

Hemophilia is a congenital X-linked bleeding disorder caused by deficiency or dysfunction of coagulation factor VIII (hemophilia A) or factor IX (hemophilia B), resulting in excessive bleeding risk that varies according to baseline factor plasma levels. 1

Disease Classification and Genetics

Hemophilia results from pathogenic variants in the genes coding for FVIII (F8 gene) or FIX (F9 gene), with most affected individuals carrying these genetic mutations. 1

• Hemophilia A accounts for approximately 80-85% of all hemophilia cases, while hemophilia B represents the remaining 15-20% 1
• The estimated prevalence at birth is 24.6 cases per 100,000 males for hemophilia A and 5.0 cases per 100,000 males for hemophilia B 1
• Worldwide, an estimated 1,125,000 individuals are affected by hemophilia 1

Severity Classification

Hemophilia severity is classified based on baseline clotting factor plasma levels, which directly correlates with bleeding risk: 1

• Severe hemophilia: Factor levels <1 international unit (IU)/dL 1
• Moderate hemophilia: Factor levels 1-5 IU/dL 1
• Mild hemophilia: Factor levels >5-40 IU/dL 1

Clinical Manifestations

The bleeding phenotype varies according to disease severity, with severe forms causing the most significant morbidity: 1

• Individuals with severe hemophilia not receiving prophylaxis experience spontaneous bleeding, most frequently affecting joints and muscles 1
• Moderate hemophilia typically presents with an intermediate bleeding phenotype, though some patients may have clinical manifestations similar to severe disease 1
• Mild hemophilia patients generally bleed only with surgical procedures or trauma 1
• Recurrent joint and muscle bleeds lead to progressive musculoskeletal damage and hemophilic arthropathy 2, 3

Treatment Complications

The development of neutralizing alloantibodies (inhibitors) against infused clotting factor concentrates represents the most serious treatment complication: 1, 4

• The cumulative incidence of inhibitors is 20-35% in severe hemophilia A patients 1, 4
• Inhibitor development is lower in severe hemophilia B, occurring in 4-9% of patients 1
• Main risk factors for inhibitor development include hemophilia severity, F8/F9 genotype, and cumulative exposure to clotting factor concentrates 1
• Bypassing agents such as recombinant activated FVII and activated prothrombin complex concentrate are used when bleeding does not respond to standard replacement therapy in patients with inhibitors 1, 4