Hemophilia is a genetic disorder that impairs the blood’s ability to clot, leading to prolonged bleeding after injury or surgery, and often spontaneous internal bleeding. The condition stems from a deficiency in specific clotting proteins, most commonly Factor VIII (Hemophilia A) or Factor IX (Hemophilia B). Since this condition is genetic, preventing its existence entirely is not possible. Prevention efforts focus on two main areas: stopping the transmission of the gene to the next generation and preventing severe outcomes and complications in individuals who have the disorder.
Understanding the Genetic Basis
Hemophilia A and B are inherited disorders caused by mutations in genes located on the X chromosome, making them X-linked recessive conditions. The gene for Factor VIII (F8) causes Hemophilia A, while the gene for Factor IX (F9) causes Hemophilia B. Since males possess only one X chromosome, a single altered copy of the F8 or F9 gene is sufficient to cause the condition.
Conversely, females have two X chromosomes. They typically need an altered copy of the gene on both chromosomes to have severe hemophilia, which is rare. More commonly, a female with one altered gene copy is a carrier who may not experience bleeding symptoms or may have mild symptoms, such as heavy menstrual periods. A male child born to a female carrier has a 50% chance of inheriting the altered X chromosome and thus having hemophilia. A father with hemophilia cannot pass the condition to his sons, but all his daughters will automatically be carriers.
Severe hemophilia is characterized by factor activity levels below 1% of normal, leading to frequent, spontaneous bleeding episodes. Moderate hemophilia involves factor levels between 1% and 5%, while mild hemophilia has levels above 5%, often only resulting in bleeding after trauma or surgery.
Preventing Genetic Transmission
For prospective parents with a family history of the disorder or those who are known carriers, several proactive medical strategies exist to avoid passing the condition to their children. Genetic counseling is the initial step, allowing couples to understand their specific risk based on their family’s mutation and explore all reproductive options before conception or during pregnancy.
Carrier testing involves DNA analysis to identify the specific mutation in the F8 or F9 gene. Identifying the exact genetic change, such as the common intron 22 inversion for Hemophilia A, informs the most accurate testing pathway.
Preimplantation Genetic Diagnosis (PGD) is used with In Vitro Fertilization (IVF) to select embryos that do not carry the hemophilia gene. After eggs are fertilized, the resulting embryos are biopsied, and a single cell is tested for the known mutation. Only unaffected embryos are transferred to the uterus, eliminating the risk of an affected pregnancy.
For couples who conceive naturally, prenatal diagnosis offers the option to test the fetus during pregnancy. Non-invasive methods, such as cell-free fetal DNA testing, can determine the sex of the fetus as early as nine weeks, which is relevant since males are primarily affected. If the fetus is male, more invasive testing, such as Chorionic Villus Sampling (CVS) or amniocentesis, can check for the specific gene mutation. CVS is typically done between 11 and 14 weeks, while amniocentesis is performed around 15 to 20 weeks; both carry a slight risk of miscarriage.
Preventing Bleeding Episodes and Complications
For individuals diagnosed with hemophilia, the primary focus is preventing bleeds and the long-term damage they cause, particularly to the joints. The gold standard is prophylaxis, which involves the regular, scheduled infusion of the missing clotting factor concentrate. Prophylaxis is typically started early in life, ideally before the age of three and before the onset of permanent joint damage, known as primary prophylaxis.
The goal of prophylaxis is to maintain the trough factor level—the lowest concentration of the clotting factor in the blood—at a minimum of 1% to prevent spontaneous bleeding. Standard treatment for Hemophilia A involves infusing Factor VIII three times per week, while Factor IX for Hemophilia B is infused twice weekly due to its longer half-life. Extended half-life factor products and non-factor therapies, such as the bispecific antibody emicizumab for Hemophilia A, have made less frequent dosing possible.
Lifestyle and safety modifications are necessary to minimize the risk of trauma-induced bleeds. Patients should avoid high-impact contact sports like football or wrestling, opting instead for safe activities such as swimming, walking, or golf. Maintaining a healthy weight is important because excess body weight places undue stress on the joints, making them more vulnerable to damage from bleeding.
Attention to medication use and dental health is a necessary aspect of preventive care. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin must be avoided because they interfere with platelet function and worsen bleeding. Consistent dental hygiene is required to prevent gum disease, which could cause excessive or prolonged bleeding.
All individuals with hemophilia are advised to receive vaccinations for Hepatitis A and Hepatitis B. While modern factor concentrates are manufactured using recombinant technology and are much safer than past plasma-derived products, vaccination remains a universal precaution. Vaccines should generally be administered subcutaneously, or under the skin, instead of intramuscularly to minimize the risk of a muscle bleed.
Finally, a detailed emergency plan is essential for rapid response to bleeds. This plan should include having factor concentrate readily accessible for home treatment and knowing the exact target factor level required for various types of bleeds. Patients should receive care at a comprehensive hemophilia treatment center, which provides a multidisciplinary team for ongoing monitoring and education.