Hemophilia is a rare X-linked congenital bleeding disorder characterized by a deficiency of coagulation factor VIII (FVIII), called hemophilia A, or factor IX (FIX), called hemophilia B. The factor deficiencies are the result of pathogenic variants in the F8 and F9 clotting factor genes.
The best estimates of the prevalence of hemophilia, based on the most reliable national patient registry data available and recent World Federation of Hemophilia (WFH) annual global surveys, indicate that the expected number of males with hemophilia worldwide is 1,125,000, the majority of whom are undiagnosed, including an estimated 418,000 males with severe hemophilia.
Hemophilia A and B
- Hemophilia A is much more common than hemophilia B. Hemophilia A is estimated to account for 80%-85% of all hemophilia cases; hemophilia B is estimated to account for 15%-20% of all hemophilia cases. Estimated prevalence is 17.1 cases per 100 000 males for all severities of hemophilia A (6.0 cases for severe hemophilia A) and 3.8 cases per 100 000 males for all severities of hemophilia B (1.1 cases for severe hemophilia B).1 Estimated prevalence at birth is 24.6 cases per 100 000 males for all severities of hemophilia A (9.5 cases for severe hemophilia A) and 5.0 cases per 100 000 males for all severities of hemophilia B (1.5 cases for severe hemophilia B).
- Hemophilia is usually inherited through an X chromosome with an F8 or F9 gene mutation. However, both the F8 and F9 genes are prone to new mutations, and about 30% of all cases result from spontaneous genetic variants. Prospective studies report that over 50% of people newly diagnosed with severe hemophilia have no prior family history of hemophilia.
- Hemophilia usually affects only males who inherit an affected maternal X chromosome. Females with hemophilia (FVIII or FIX <40 IU/dL) are rare; in such cases, both X chromosomes are affected or one is affected and the other is inactive. A female with one affected X chromosome is called a carrier of hemophilia.
- Hemorrhages, musculoskeletal complications, and other sequelae of hemophilia typically occur in males with hemophilia but may also occur in a proportion of female carriers. Since the baseline factor levels in carriers may be normal or variably reduced, the symptoms and complications of hemophilia are less common in females and are often overlooked and underdiagnosed; joint bleeds in carriers often remain unrecognized, leading to poorer joint outcomes due to undiagnosed joint problems. Better diagnosis and management of bleeding problems in carriers are needed.