Types of Hemophilia
Hemophilia has two main types: Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency), both X-linked recessive bleeding disorders that are further classified by severity based on clotting factor levels. 1, 2
Primary Classification by Factor Deficiency
- Hemophilia A results from deficiency of functional coagulation factor VIII (FVIII), caused by pathogenic variants in the F8 gene 1, 3
- Hemophilia B results from deficiency of functional coagulation factor IX (FIX), caused by pathogenic variants in the F9 gene 1, 3
- Hemophilia A is significantly more common, accounting for approximately 80-85% of all hemophilia cases, with an estimated prevalence of 24.6 cases per 100,000 males at birth 1
- Hemophilia B accounts for 15-20% of cases, with an estimated prevalence of 5.0 cases per 100,000 males at birth 1
Classification by Severity
Both hemophilia A and B are classified into three severity categories based on plasma factor activity levels, which directly correlate with bleeding risk and clinical presentation 1:
Severe Hemophilia
- Factor levels <1 IU/dL (<1% of normal) 1
- Patients experience spontaneous bleeding, most frequently into joints and muscles, without prophylaxis 1
- Highest risk for inhibitor development: 20-35% cumulative incidence in severe hemophilia A versus 4-9% in severe hemophilia B 1
Moderate Hemophilia
- Factor levels 1-5 IU/dL (1-5% of normal) 1
- Patients generally have an intermediate bleeding phenotype but may have a clinical phenotype similar to severe hemophilia 1
- Bleeding typically occurs with minor trauma rather than spontaneously 1
Mild Hemophilia
- Factor levels >5 to 40 IU/dL (>5-40% of normal) 1
- Patients may bleed only upon surgical procedures or significant trauma 1
- Often diagnosed later in life when challenged by surgery or injury 1
Important Clinical Distinctions
A critical limitation of severity classification is its failure to account for clinical heterogeneity in bleeding observed between individuals with the same factor levels, or between hemophilia A and B patients with equivalent factor levels. 1 This means two patients with identical factor levels may have different bleeding phenotypes, requiring individualized treatment approaches based on clinical presentation rather than laboratory values alone.
The classification of individuals with factor levels between 40-50% remains unresolved and may represent a gray zone requiring clinical judgment 1.