Complications of Hemophilia A

A person with hemophilia A can live a relatively normal life when their condition is managed well and they receive appropriate checkups at a comprehensive hemophilia treatment center.

But even with good hemophilia care, complications can develop, and when they do, they usually require immediate medical attention. Some can quickly becoming life-threatening without treatment.

According to the National Hemophilia Foundation, excessive internal bleeding is one common complication that requires medical care right away. But since you may not realize you’re bleeding internally, it’s important to talk to your doctor about the symptoms of internal bleeding and when to be concerned.

Head Injury Leading to Bleeding in the Brain

Bumps and bruises that would be minor in the average person can become very serious in a person with hemophilia A, especially if the person’s clotting factors are very low.

One of the most serious potential complications is bleeding in the brain as a result of a head injury. According to Mayo Clinic and the National Hemophilia Foundation, someone with hemophilia A should seek medical attention for a head injury if they experience any of the following symptoms:

• Double vision
• Painful headache that lasts a long time
• Neck stiffness
• Frequent vomiting
• Feeling extra sleepy or lethargic
• Feeling weak, off balance, or clumsy
• Difficulty walking
• Seizures or convulsions
• Unusual changes in behavior

Joint Damage From Repeated Bleeds

Bleeding in the joints and muscles is the most common type of bleeding with hemophilia A. (3) In the short term, this bleeding causes swelling and pain, making it difficult to move the joints.

Over the longer term, swollen muscles and blood trapped in them can put pressure on nerves, which can cause nerve damage.

Repeated bleeding in the same joint can gradually wear down the synovium, the soft tissue that lines a joint’s inner surface. With less joint space, movement becomes difficult and limited.

These problems can compound over time and develop into arthritis. People who develop severe joint damage may need joint replacement or a joint fusion surgery.

Development of Inhibitors, Antibodies to Clotting Factors

About 15 to 20 percent of people with hemophilia A (1 in 5 to 7 people) develop a complication called inhibitors. (4) Inhibitors are antibodies produced by the body’s immune system that attack the clotting factors in hemophilia treatment because the immune system sees them as foreign intruders in the body.

They therefore prevent clotting factors from doing their job — to make blood clot to stop bleeding. Having inhibitors is a bit like developing a resistance to the treatment for hemophilia A.

Bleeding episodes are much more difficult to manage and treat if a person has inhibitors. People with inhibitors may experience more pain, especially in joints and muscles, because of poorly controlled bleeding. People who use a central venous access device (CVAD), such as a Port-A-Cath, for their treatment have a much higher risk of developing an infection if they have inhibitors.

Treatment for Hemophilia A When Inhibitors Are Present

Treatment of hemophilia A with inhibitors is complex and depends on the particular person’s circumstances. (5) If a person’s levels of inhibitors are low enough, then using high doses of clotting factor concentrates can overcome the inhibitor. (6)

Another treatment for inhibitors is using bypassing agents, blood products that help the blood clot using different factors than the one blocked by inhibitors. These therapies “bypass” the blocked factors.

Two bypassing agents include activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rFVIIa), according to the National Hemophilia Foundation. aPCC is made from human plasma and includes a concoction of other clotting factors, such as factors 7 (VII), 9 (IX), and 10 (X). One risk of using it is developing a blood clot.

aPCC is usually given every 8 to 12 hours, while rFVIIa, a synthetic (man-made) product is administered every two to three hours.

Two anti-fibrinolytic (clot-promoting) drugs that can help people with inhibitors are epsilon-aminocaproic acid and tranexamic acid (Lysteda). Both are available as pills or injections. Tranexamic acid and aPCC should not be taken at the same time.

Plasmapheresis is a procedure used when a person’s concentration of inhibitors needs to go down quickly, such as before a surgery or to stop a major bleeding episode. This procedure literally removes inhibitors from the person’s bloodstream.

A more recent therapy for inhibitors is emicizumab (Hemlibra), which mimics factor 8 (VIII) by carrying out the same function but is not blocked by inhibitors.

Emicizumab is an injection given under the skin. It can be administered weekly, every other week, or every four weeks. People taking bypassing agents may need to change their treatment schedule if they begin taking emicizumab, because the risk of blood clots can increase.

The most intensive way to deal with inhibitors is to confront them head-on with immune tolerance induction (ITI) therapy. This therapy teaches the immune system to recognize the factors as a normal part of the body so that the inhibitors stop attacking them.

But ITI therapy is expensive and very involved. It requires daily injections of large amounts of factor for weeks or months, and it can take one to two years to clear a person of inhibitors. (5) It can be risky to take breaks from the therapy or miss treatments because that stops training the immune system to accept the factor as a normal part of the body.

ITI does not work in everyone, and may be less successful for those with mild to moderate hemophilia A. But ITI can be 70 to 80 percent effective for those with severe hemophilia A, according to the World Federation of Hemophilia. ITI is more likely to work in people with any of the following characteristics:

• The person’s inhibitor levels never went higher than 200 BU/mL and have ideally stayed below 50 BU/mL.
• Inhibitor diagnosis was within the previous five years (7)

Causes and Risk Factors for Inhibitors

The reason some people develop inhibitors and others do not is not clear. Some research has shown an increased risk of inhibitors in people with certain gene mutations. (9)

Other research has identified the following risk factors for developing inhibitors:

• Number of times a person has received clotting factor concentrates treatment in their life to date
• Receiving a higher dose of therapy or receiving it more frequently
• Family history of inhibitors
• Being black or Hispanic

People with hemophilia A should be tested for inhibitors once a year. (4) Federally funded hemophilia treatment centers provide free inhibitors testing to people who participate in the CDC’s Community Counts Registry for Bleeding Disorders Surveillance program. ( 10)

A blood test is used to diagnose the presence of inhibitors. The proportion of inhibitors that exist is called the inhibitor titer.