Hemophilia A is the most common X-linked genetic disease and the second most common factor deficiency

after von Willebrand disease (vWD). The worldwide incidence of hemophilia A is approximately 1 case per
5000 males, with approximately one third of affected individuals not having a family history of the disorder.
The prevalence of hemophilia A varies with the reporting country, with a range of 5.4-14.5 cases per
100,000 males.
In the United States, the prevalence of hemophilia A is 20.6 cases per 100,000 males. In 2013, the number
of people in the United States with hemophilia was estimated to be about 20,000. [14]
Approximately 50-60% of patients have severe hemophilia A (FVIII < 2% of normal), associated with the
severest bleeding manifestations. Approximately 25-30% have moderate hemophilia (FVIII 2-5%) and
manifest bleeding after minor trauma. Those with mild hemophilia A (FVIII 6-30%) comprise 15-20% of all
people with hemophilia; these patients develop bleeding only after significant trauma or surgery.
Acquired hemophilia A, caused by the development of an autoantibody to FVIII in a person with previously
normal hemostasis, develops with a frequency of 1 case per 1 million population per year.[15] Acquired FVIII
deficiency is observed in older populations, generally those older than 60 years.
The inherited, combined deficiency of factors V and VIII is a rare but recognized cause of a bleeding
disorder. The prevalence is estimated to be 1 case per million population. [13]

Racial, sexual, and age-related differences in incidence

Hemophilia A occurs in all races and ethnic groups. In general, the demographics of hemophilia follow the
racial distribution in a given population; for example, rates of hemophilia among whites, African Americans,
and Hispanics in the US are similar.
Because hemophilia is an X-linked, recessive condition, it occurs predominantly in males. Females usually
are asymptomatic carriers. However, mild hemophilia may be more common in carriers than previously
recognized. In 1 study, 5 of 55 patients with mild hemophilia (factor levels 5-50%) were girls. [16]
Females may have clinical bleeding due to hemophilia if any of the following 3 conditions is present:

Extreme lyonization (ie, inactivation of the normal FVIII allele in one of the X chromosomes) [17]
Homozygosity for the hemophilia gene (ie, father with hemophilia and mother who is a carrier, two
independent mutations, or some combination of inheritance and new mutations)

Turner syndrome (XO) associated with the affected hemophilia gene

In genetic cases, significant deficiency in FVIII may be evident in the neonatal period. It continues through
the life of the affected individual. The absence of hemorrhagic manifestations at birth does not exclude
hemophilia.