Bleeding disorders like hemophilia affect the body’s ability to create blood clots. The formation of appropriate blood clots is necessary to allow injuries to heal. People with a bleeding disorder may experience a range of symptoms from easy bruising to life threatening bleeding following surgery or injury. This excessive bleeding is primarily due to one or more abnormal clotting factors in the blood. Given the potential severity of the condition, preimplantation genetic testing (PGT) has been used by individuals with a family history of hemophilia to reduce the risk of passing the disease down to the next generation.
What is Hemophilia?
Hemophilia is a genetic bleeding disorder that can cause mild to severe bleeding depending on the type and amount of clotting factor that is impacted. According to the CDC, severe hemophilia is typically diagnosed by one month of age whereas mild hemophilia may remain undetected until closer to the toddler years when an atypical bleeding episode warrants further testing. Individuals with hemophilia may experience prolonged bleeding following surgery, injury, or having dental work. Those with severe hemophilia may also have spontaneous bleeding that is not related to an injury or other obvious cause.
There are two major types of hemophilia – hemophilia A and B. Both forms result in similar symptoms, but they are caused by mutations in two different genes.
How are hemophilia A and B inherited?
Both hemophilia A and B are X-linked diseases. The genes that cause hemophilia are located on the X chromosome. Hemophilia A is caused by variants in the F8 gene while hemophilia B results from variants in the F9 gene. X-linked conditions affect males in far greater numbers than females. Since females have two X chromosomes, their body may still be able to produce enough clotting factor with only one working copy of the F8 or F9 gene despite having a disease-causing variant in the other. Males, however, only have one X chromosome leaving them far more susceptible to the disease-causing effects of these variants. Hemophilia A is the more common form of the disorder, and it is estimated that it affects approximately 1 in 5,000 males worldwide.
Males inherit their X chromosome from their mother and their Y chromosome from their father. In about ⅔ of cases, there is a family history of hemophilia and a variant can be identified in an affected individual’s mother. In the remaining ⅓ of cases, it is expected that hemophilia is caused by a de novo, or new variant that was not passed down through the family. This is an important consideration for PGT as de novo cases of hemophilia in a previous child or family member would not be expected to increase the risk for a future pregnancy to be affected.
How are hemophilia A and B treated?
The primary treatment for hemophilia is called replacement therapy. In this type of therapy, the goal is to replace or supplement the missing clotting factor. A concentrated version of the clotting factor, either F8 in hemophilia A or F9 in hemophilia B, is given via infusion. Some people receive clotting factors on a regular basis in an effort to prevent excessive bleeding episodes. For others, this is only necessary when bleeding occurs. These infusions can take place at home or at an infusion center.
Another treatment that is used in individuals with mild to moderate hemophilia is called Desmopressin (DDAVP). DDAVP is a hormone that stimulates the release of stored F8. It is typically given as an injection or nasal spray. Because it is possible to become resistant to DDAVP, it is generally given only in specific situations where the risk of bleeding is likely to be increased.
Is preimplantation genetic testing (PGT) available for hemophilia A or B?
Yes. PGT (also referred to as preimplantation genetic diagnosis or PGD) is available for couples who are at increased risk to have a child with hemophilia A or B. Historically, PGT has been done primarily through sex selection of embryos. Since hemophilia is X-linked, selecting only female embryos effectively prevents transmission of the disease. However, this limits couples to only having female children. Research shows that testing each embryo for hemophilia status instead of general sex selection greatly increases the number of embryos available for transfer and allows prioritization of unaffected male and female embryos. This is advantageous as transferring the embryos of carrier females could result in the condition being passed down to the next generation. Hemophilia is commonly included by fertility clinics in their PGT program.
Jessica Greenwood is an independent consultant to Sharing Health Genes. As a licensed genetic counselor and digital health consultant, she works with health-related organizations looking to deliver memorable messages of health in the digital space. Mrs. Greenwood started her career in a clinical role, working for eight years as a preconception and prenatal genetic counselor before transitioning to industry. Mrs. Greenwood completed a year-long certificate program in Digital Health Communication at Tufts University that spearheaded her work in digital health. She now consults with health-related organizations, assisting with the creation and execution of a digital strategy including the development of health literate patient-centered educational materials. Mrs. Greenwood earned a Bachelor of Science degree from North Carolina State University with a minor in Genetics and a Master of Science in Genetic Counseling from the University of North Carolina at Greensboro.