Hemophilia is an inherited bleeding disorder caused by a deficiency of one of two blood clotting factors, which make a person’s blood clot. People with hemophilia can bleed spontaneously into their muscles and joints, and have life-threatening bleeds into their brain or other organs. The most common forms of hemophilia are deficiencies of blood clotting factors 8 and 9, commonly known as hemophilia A and B.

Where genetics fit in

Hemophilia is a sex-linked disorder, where the genes for both factors 8 and 9 are located on the X chromosome. Because males have only one X chromosome versus two in females, males generally have more severe hemophilia, although affected females may also have bleeding symptoms.

People with hemophilia treat their disorder by injecting the missing blood clotting factor into their vein. Determination of the factor 8 and factor 9 genes in the 1980s led to development of a manufactured, non-blood-containing recombinant factor replacement product. This decreased the need for use of products developed from whole blood donations.

“Research into hemophilia has shown that it is caused by many different mutations in the gene.”

Research into hemophilia has shown that it is caused by many different mutations in the gene. Therefore, by genotyping — a blood test to find a specific mutation — a person can discover the specific defect that causes their hemophilia. This information can be used to determine inheritance patterns in a person’s family, whether they are prone to certain complications, and severity of bleeding.

A new phase of therapy      

Our understanding of the genetics of hemophilia has paved the way for new therapies including new factor replacement products that work better and last longer. Gene therapies are being investigated, where a normal factor 8 or factor 9 gene is introduced into the body.

Hemophilia is a rare disease, affecting approximately 20,000 people in the United States. In rare genetic diseases, it is critical to have many patients genotyped and then relate scientific findings with how the disease affects an individual patient. A national genotyping study is currently underway in the United States. The U.S. National Institutes of Health is supporting important studies to understand how other genes interact and their impact on diseases, such as hemophilia. This work includes sequencing of the entire genetic code in an affected patient to allow for future research — or genomics.

Knowing how an individual’s genes affect the risk of bleeding and response to treatment paves the way for a better tomorrow for patients and their families.