From the Guidelines
Yes, women can develop hemophilia, though it is rare, and all treatment recommendations for congenital hemophilia A and B also apply to women with low plasma levels of FVIII or FIX and a propensity toward bleeding. Hemophilia is primarily an X-linked recessive bleeding disorder, meaning the defective gene is located on the X chromosome. Since women have two X chromosomes, they typically need to inherit the defective gene from both parents to develop the condition. This is why hemophilia is much more common in males, who have only one X chromosome and will develop the disorder if they inherit the defective gene from their mother. However, women can be symptomatic carriers, experiencing mild to moderate bleeding symptoms due to having one normal and one affected X chromosome. In rare cases, women can develop hemophilia through several mechanisms: inheriting the defective gene from both parents, having Turner syndrome (only one X chromosome), or through extreme lyonization (inactivation of the normal X chromosome) 1.
Key Points to Consider
- Women with hemophilia may experience prolonged bleeding after injury, easy bruising, and spontaneous bleeding into joints and muscles.
- Diagnosis and treatment are similar to those for men, including factor replacement therapy and other medications to control bleeding, such as emicizumab for patients with severe hemophilia A with and without inhibitors 1.
- The cumulative incidence of inhibitors is higher for patients with severe hemophilia A (20%-35%) than with severe hemophilia B (4%-9%), and treatment with bypassing agents such as recombinant activated FVII (FVIIa) and activated prothrombin complex concentrate can be used to treat patients with inhibitors whose bleeding does not respond to replacement of the deficient factor 1.
- All the recommendations in the guideline, whether strong or conditional, also apply to women who have low plasma levels of FVIII or FIX and a propensity toward bleeding 1.
From the Research
Hemophilia in Women
- Hemophilia is typically considered a male-dominated disorder, but women can also be affected, particularly those who are carriers of the hemophilia gene 2, 3.
- Female carriers of hemophilia A may have factor VIII levels below 0.5 IU/dL, which can lead to mild hemophilia symptoms, including menorrhagia and bleeding after childbirth 2.
- In some cases, females with hemophilia may go undiagnosed for years due to the similarity of their symptoms to those experienced by women without hemophilia 2.
- Skewed X-chromosome inactivation can also lead to the manifestation of hemophilia in carrier females, resulting in a range of symptoms from mild to severe 3.
Severity and Management
- The severity of hemophilia symptoms in women is directly proportional to the level of clotting factor in the blood 3.
- Prophylactic factor replacement therapy is recommended for females with hemophilia, particularly those with joint disease or gynecologic complications 2.
- Education and infusion training are essential for affected individuals to manage their condition effectively and recognize bleeding symptoms that require treatment 2.
- Novel therapeutic approaches, such as inhibition of tissue factor pathway inhibitor, are being explored to improve hemophilia management and quality of life for affected individuals 4.