Hemophilia Types
There are two main types of congenital hemophilia: Hemophilia A (Factor VIII deficiency) and Hemophilia B (Factor IX deficiency), with each further classified by severity based on clotting factor levels. 1
Primary Classification
The two distinct types of hemophilia are:
Hemophilia A: Results from deficiency of functional coagulation Factor VIII, caused by pathogenic variants in the F8 gene. This accounts for 80-85% of all hemophilia cases 1
Hemophilia B: Results from deficiency of functional coagulation Factor IX, caused by pathogenic variants in the F9 gene. This represents the remaining 15-20% of cases 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.
Severity Classification
Both hemophilia A and B use identical severity classifications based on plasma factor levels 2, 1:
- Severe: Factor levels <1 IU/dL (<1% of normal)
- Moderate: Factor levels 1-5 IU/dL (1-5% of normal)
- Mild: Factor levels >5 to 40 IU/dL (>5-40% of normal)
This classification correlates well with clinical bleeding profiles in most cases and remains the standard approach 2.
Clinical Distinctions Between Types
While traditionally considered clinically indistinguishable, hemophilia A and B do show important differences 3:
Bleeding patterns differ:
- Severe hemophilia patients experience spontaneous bleeding, most frequently into joints and muscles 1
- Moderate hemophilia patients have an intermediate phenotype but may present similarly to severe disease 1
- Mild hemophilia patients typically bleed only with surgical procedures or trauma 1
Inhibitor development rates vary significantly:
- Hemophilia A: 20-35% cumulative incidence in severe cases 1
- Hemophilia B: 4-9% cumulative incidence in severe cases 1
Critical treatment consideration: Patients with hemophilia B and inhibitors may develop anaphylactic reactions to activated prothrombin complex concentrate, requiring use of recombinant FVIIa exclusively 1.
Important Caveats
- The severity classification has limitations—it fails to account for clinical heterogeneity in bleeding observed among individuals with the same factor levels 2
- Classification of individuals with Factor VIII levels between 40-50% remains unresolved 2
- Women can also be affected when they have low plasma levels of Factor VIII or IX with bleeding tendency 1
- The type of Factor VIII/IX mutation is a major determinant of both bleeding tendency and inhibitor formation risk 3