From the Guidelines
Factor 8 deficiency, also known as hemophilia A, is an inherited bleeding disorder caused by insufficient levels of clotting factor VIII in the blood, primarily affecting males and classified as severe, moderate, or mild based on factor VIII levels. This condition results from a complete or partial deficiency of blood coagulation factor VIII due to pathogenic variants in the F8 gene, as stated in the study by 1. People with factor 8 deficiency have difficulty forming blood clots, resulting in prolonged bleeding after injuries, surgeries, or sometimes spontaneously. The severity varies based on factor VIII levels: severe (<1%), moderate (1-5%), or mild (5-40%) 2.
Treatment Options
Treatment involves replacing the missing factor VIII through intravenous infusions of factor concentrates, either on-demand for bleeding episodes or as prophylaxis to prevent bleeds. Common factor VIII products include Advate, Eloctate, Kogenate, and Recombinate, with dosing based on weight, severity, and bleeding location. Some patients develop inhibitors (antibodies) against factor VIII, requiring alternative treatments like bypassing agents (NovoSeven, FEIBA) or immune tolerance therapy, as discussed in the study by 3.
Management and Prophylaxis
Regular comprehensive care with a hematologist is essential for managing this lifelong condition. Prophylaxis with factor VIII concentrates or emicizumab can be effective in preventing bleeds, especially in individuals with severe hemophilia A, as shown in the study by 4. The choice of prophylaxis should be guided by availability, resources, costs, values, and preferences. In settings where previously untreated individuals with severe hemophilia A will start prophylaxis, the panel suggests initial prophylaxis with plasma-derived FVIII over standard half-life recombinant FVIII, as recommended in the study by 4.
Key Considerations
Gene therapy shows promise as a potential cure, though it's still under development. The main complication of hemophilia A treatment is the development of neutralizing antibodies to FVIII, so-called inhibitors, which can be mitigated with appropriate treatment strategies, as discussed in the study by 5. Overall, managing factor 8 deficiency requires a comprehensive approach, including regular monitoring, prophylaxis, and treatment of bleeding episodes, as well as consideration of the potential complications and emerging therapies, as outlined in the studies by 1, 3, 2, 5, 4, 6.
From the FDA Drug Label
Factor VIII is the specific clotting factor deficient in patients with hemophilia A (classical hemophilia). Hemophilia A is a genetic bleeding disorder characterized by hemorrhages, which may occur spontaneously or after minor trauma Factor 8 deficiency is a condition where the body is missing or has low levels of Factor VIII, a clotting factor necessary for blood to clot normally. This deficiency is characteristic of Hemophilia A, a genetic bleeding disorder that can cause hemorrhages to occur spontaneously or after minor trauma. 7
From the Research
Definition of Factor 8 Deficiency
- Factor 8 deficiency, also known as Hemophilia A, is a genetic disorder caused by a deficiency of clotting factor VIII 8.
- It is a common hereditary disorder that affects approximately 1 in 10,000 males 9.
- The disorder is characterized by the inability of blood to clot properly, leading to prolonged bleeding 10.
Causes of Factor 8 Deficiency
- The most common cause of factor 8 deficiency is an inversion of the factor VIII gene, which accounts for nearly 45% of patients with severe hemophilia A 8.
- Other mutations in the factor VIII gene can also cause the disorder 8.
Treatment of Factor 8 Deficiency
- The primary treatment for factor 8 deficiency is replacement therapy with factor VIII concentrates [(10, 9, 11)].
- There are two types of factor VIII concentrates: plasma-derived and recombinant [(10, 9)].
- Recombinant factor VIII has been shown to be safe and effective for the treatment of hemophilia A 9.
- However, recombinant factor VIII has also been associated with a higher risk of inhibitor development compared to plasma-derived factor VIII 10.