Hemophilia A is a genetic bleeding disorder that primarily affects males. It is caused by a deficiency or dysfunction of clotting factor VIII, an essential protein for blood clotting. Hemophilia A is inherited in an X-linked recessive manner, meaning the defective gene responsible for the condition is on the X chromosome. The prevalence of hemophilia A is estimated to be about 1 in 6,000 male individuals.
Hemophilia A genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of Hemophilia A include:
- Clotting Factor VIII Deficiency: Individuals with Hemophilia A have insufficient levels or impaired function of clotting factor VIII. This deficiency impairs blood clotting, leading to prolonged bleeding after injuries or spontaneous bleeding into joints and muscles.
- Bleeding Episodes: The hallmark of Hemophilia A is spontaneous or excessive bleeding. Common sites for bleeding include joints (hemarthrosis), muscles, and soft tissues. Individuals may experience easy bruising, prolonged bleeding from minor cuts or injuries, and, in severe cases, spontaneous bleeding without an apparent cause.
- Joint Damage: Recurrent bleeding into joints, particularly the knees, elbows, and ankles, can damage joints over time. This can result in chronic joint pain and limited range of motion.
- Inheritance Pattern: Hemophilia A is inherited in an X-linked recessive manner. Females typically carry the defective gene on one of their X chromosomes, while males have one X and one Y chromosome. Males with the faulty gene will have Hemophilia A, while females are typically carriers unless they inherit two affected X chromosomes (which is rare).
- Severity Grading: The severity of Hemophilia A is classified into three categories based on the amount of clotting factor VIII in the blood:
- Mild: Factor VIII levels are between 5% and 40%.
- Moderate: Factor VIII levels are between 1% and 5%.
- Severe: Factor VIII levels are less than 1%.
Management of Hemophilia A involves replacing the missing or deficient clotting factor VIII through infusions of recombinant or plasma-derived factor VIII concentrates. This is known as factor replacement therapy and is tailored to the severity of the condition and the specific needs of the individual. Prophylactic (preventive) factor replacement therapy may be recommended to prevent bleeding episodes.
Additionally, supportive measures include managing bleeding episodes as they occur, using joint protection strategies, and using physical therapy to maintain joint function.
Advances in treatment, including the development of factor concentrates and improved management strategies, have significantly improved the quality of life for individuals with Hemophilia A. Regular follow-up with a hematologist and comprehensive care are essential components of managing this condition. Genetic counseling is also necessary for families affected by Hemophilia A to understand the inheritance pattern and make informed decisions about family planning.
More Information
Coagulation factor VIII (FVIII) is a plasma glycoprotein involved in blood coagulation and encoded by the F8 gene. This factor acts as a coenzyme that accelerates the generation of factor Xa and thrombin. Thrombin is the enzyme that converts fibrinogen (soluble) to fibrin (insoluble) during blood clotting.
In affected families, males with the disease inherit a copy of the mutated F8 gene from their carrier mothers. There is a 50% chance that a carrier mother will pass on the defective F8 gene to her son. All female offspring born to a hemophilic father are carriers. However, the possibility of families with sporadic hemophilia (approximately 10%) due to a spontaneous mutation in individuals whose parents do not appear to be carriers should be considered.
More than 60% of the mutations in the F8 gene are single-nucleotide variants (SNPs), which is the type of alteration analyzed in our test. Other alterations have also been described in the F8 gene, such as tandem repeats of variable numbers and inversions of intron 1 or intron 22, which are present in 45-50% of patients with severe disease.
Hemophilia A genetic testing analyzes the 20 most frequent pathogenic mutations of the F8 gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
