Hemophilia is a rare inherited bleeding disorder where the body cannot form blood clots due to insufficient levels of specific clotting factors. While predominantly affecting males, females can also be affected. Understanding hemophilia in females provides a complete picture of its presentation and management.
The Genetic Basis of Hemophilia
Hemophilia A and B are primarily inherited in an X-linked recessive pattern. The genes for clotting factors VIII (F8) and IX (F9) are on the X chromosome. Males have one X and one Y chromosome; females have two X chromosomes. Since males have only one X chromosome, a single altered gene on that chromosome is sufficient for them to develop hemophilia.
Conversely, females have two X chromosomes. If one X chromosome carries the altered gene, the other often has a functional copy that can compensate. This typically makes females carriers, not experiencing full-blown hemophilia. As carriers, they can pass the altered gene to their children. Approximately one-third of hemophilia cases result from new genetic mutations, meaning there might be no prior family history.
Hemophilia in Females
While hemophilia is less common in females, they can indeed be affected, ranging from experiencing bleeding symptoms as carriers to, in rare instances, having the full condition. Females who carry the hemophilia gene can have varying levels of clotting factors. Those with lower factor levels may experience bleeding symptoms.
This often occurs due to X-inactivation (lyonization), where one of the two X chromosomes in each cell is randomly silenced. If a significant proportion of cells inactivate the X chromosome carrying the functional clotting factor gene, the X chromosome with the altered gene becomes more active, leading to lower overall clotting factor levels. Symptomatic carriers may experience easy bruising, prolonged nosebleeds, or heavy menstrual bleeding (menorrhagia). Other bleeding can include prolonged bleeding after surgeries, dental procedures, or childbirth.
True hemophilia in females is rare but can occur under specific circumstances. One scenario involves inheriting an affected X chromosome from both parents, meaning the mother is a carrier and the father has hemophilia. Another rare instance is when a female has only one X chromosome, as seen in Turner syndrome (XO), and that single X chromosome carries the altered hemophilia gene. Additionally, extreme skewed X-inactivation, where almost all cells preferentially inactivate the normal X chromosome, can lead to factor levels low enough to cause severe bleeding, similar to males with hemophilia.
Diagnosis and Management for Females
Diagnosing hemophilia or carrier status in females involves a combination of genetic testing and clotting factor level assays. Genetic testing is the most reliable method for confirming carrier status or a diagnosis of hemophilia, identifying specific genetic changes in the F8 or F9 genes. Factor level testing measures functional clotting factor in the blood, helping determine bleeding disorder severity. However, a normal factor level does not rule out carrier status, as some carriers have sufficient factor levels but still carry the gene alteration.
Management for females with hemophilia or symptomatic carrier status focuses on their specific bleeding challenges. Heavy menstrual bleeding is a common concern and can be managed with hormonal therapies or antifibrinolytic drugs. Precautions are important during surgical procedures, including dental work, and especially during childbirth. Women with hemophilia or those who are symptomatic carriers should be monitored closely during pregnancy and delivery due to an increased risk of bleeding, including postpartum hemorrhage. A multidisciplinary healthcare team, often including hematologists and obstetricians, provides comprehensive care.