Hemophilia

Hemophilia is a bleeding disorder that slows the body’s ability to form blood clots. When most people bleed, their body naturally forms a clot that stops the bleeding. Creation of a blood clot is made possible by a number of different clotting factor proteins — von Willebrand factor and platelets all working together. In hemophilia, the body doesn't make enough of one of the clotting factors. As a result, a person with hemophilia may bleed for a longer time internally in the joints and muscles, following an injury or — in severe cases — spontaneously.

The two most common types are hemophilia A and hemophilia B. Hemophilia A is diagnosed when the levels of clotting factor VIII (8) are absent or low. Hemophilia B, also known as Christmas disease, is less common and is caused by absent or low levels of clotting factor IX (9). Depending on the level of factor activity measured in the blood, hemophilia can be mild, moderate or severe.  A person born with hemophilia will have it for life.

Hemophilia is usually hereditary and most often occurs in males because the genes for both factor VIII and factor IX are located on the X-chromosome. There is currently no cure for hemophilia, but treatments are available to prevent and treat bleed events and minimize the complications associated with hemophilia.

The symptoms and signs of hemophilia A and B are similar and may include:

• Large bruises, known as a hematoma, caused by bleeding under the skin
• Spontaneous or injury related bleeding into the muscles or joints, causing swelling and tightness
• Bleeding of the mouth and gums following tooth extractions or surgery
• Bleeding following vaccinations or shots
• Blood in the urine or stool
• Frequent and difficult-to-stop nosebleeds

A mutation or change in the gene that regulates the production of factor VIII or IX causes hemophilia. These particular genes related to clotting factors are located on the X chromosome. Females have two X chromosomes (XX), and males have one X and one Y (XY). A father will pass a hemophilia gene only to daughters; however, mothers can pass a hemophilia gene to sons or daughters.

A male who has an abnormal copy of this gene on his x chromosome will not be able to make clotting factor. This is hemophilia. Because females have two x chromosomes, they almost always have at least one working copy of the gene. This is why they are much less likely to have hemophilia.

A female who has the “hemophilia gene” on just one of her X chromosomes is less likely to have hemophilia, because her other X chromosome typically will have a normal copy of the factor gene and allow for normal factor production. While females with the hemophilia gene, called “hemophilia carriers,” have the potential to pass the hemophilia gene to their offspring, it is important to understand that some female carriers may also have low factor VIII or IX levels and have mild hemophilia and abnormal bleeding symptoms. In some rare cases, females can also have more severe forms of hemophilia.

Although hemophilia is primarily an inherited condition, about one third of cases rise from a new mutation, so there will not be any family history of hemophilia or related bleeding symptoms.

Since hemophilia can affect multiple family members and generations of family, the first step to diagnosis is learning more about both the bleeding history and a history of bleeding among immediate and extended family members. This will help your doctor determine if your family has bleeding problems.

Testing for hemophilia typically includes a physical examination to rule out other conditions, routine blood tests, and often more specialized blood tests, specifically for clotting factors. The tests will determine:

• If blood is clotting properly
• Clotting factor levels (low or missing)
• The type of hemophilia
• The severity of hemophilia

The type of treatment you or your child receive is dependent on the type and severity of the hemophilia.

Factor replacement therapy

Concentrated forms for both factor VIII (for hemophilia A) and IX (for hemophilia B) are available, so a missing clotting factor can be simply replaced through an intravenous (IV) infusion. This type of therapy is the most common treatment option for moderate and severe hemophilia. There are many different factor VIII and factor IX clotting factors available. Your clinician will work with you to learn what factor concentrate will work best.

For severe and some moderate hemophilia patients, it is important to regularly provide factor replacement to prevent bleed events. When factor therapy is given on a regular basis to prevent bleeding, it is called prophylaxis or prophylactic therapy. Typically, if you or your child receives prophylaxis, you are able to learn the skills to infuse factor replacement at home.

Generally, those with mild or moderate hemophilia only require factor replacement prior to a known situation that puts them at risk of bleeding, such as a surgery or dental procedure, or if they have an injury. This use of factor replacement is referred to as “on-demand therapy.”

Hemlibra® (emicizumab)

Emicizumab is a new, alterative medication for prophylaxis for patients with hemophilia A. Emicizumab is designed to mimic many of the functions of factor VIII (8). It is given as an injection under the skin rather than into a vein. It is not intended to treat a bleed event or provide adequate bleed protection at the time of surgeries.

Desmopressin (DDAVP or Stimate)

In mild to moderate cases of hemophilia, DDAVP may be another bleed-treatment option. This medication can be given through a vein or nasal spray, and it works by stimulating the release of factor VIII from the body’s cells. DDAVP works well for boosting factor VIII levels prior to minor surgeries for mild to moderate bleed events. Because the body’s extra factor VIII stores are depleted quickly, it cannot be used for more than three consecutive days. Also, DDAVP alters the way the kidney manages water and salt, so caution is needed with fluid intake and physical activity after use.

Antifibrinolytic medications

Antifibrinolytic medicines, including tranexamic acid and epsilon aminocaproic acid, help to make blood clots firmer. They can be used alone or with DDAVP or factor replacement therapy. Antifibrinolytic medications are most frequently used following dental work or to treat mouth or nose bleeding. These medications can be given by mouth or as an IV.

Hemophilia gene therapy

Gene therapy can correct missing or abnormal blood clotting factors at levels sufficient to curb bleeding episodes and reduce or eliminate the need for factor replacement. Boston Children’s Gene Therapy Program is now offering a gene therapy called ROCTAVIAN® for men with severe hemophilia A. Recently approved by the Food and Drug Administration, it uses a viral vector to deliver the gene for the clotting Factor VIII. It is given through an IV infusion.

In addition, Boston Children’s is participating in a clinical trial of a gene therapy treatment for hemophilia A using an adeno-associated viral vector to deliver a healthy factor VIII gene.

Learn more about gene therapy and contact gene.therapy@childrens.harvard.edu for more information.

We care for patients who have hemophilia and other bleeding disorders at the Boston Bleeding Disorders Center, a federally supported hemophilia treatment center (HTC). Our HTC is a joint program between Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Brigham and Women's Physician Organization.

The Boston Bleeding Disorders Center is the largest hemophilia treatment program in New England, offering a comprehensive care model that ensures every aspect of you or your child's health is monitored by experienced pediatric caregivers. Our goal is to enable children, adolescents and young adults with hemophilia and other bleeding disorders to manage their bleeding symptoms as independently as possible and therefore lead more normal, healthy lives.