Inhibitors are relatively uncommon. If one develops, it’s usually detected when a child with hemophilia is young, usually in the first one to three years of life. The median time to development of an inhibitor is about nine to eleven exposure days— days on which the child received one or more infusions of factor VIII or factor IX. Parents may suspect that something is wrong, usually because a bleed will not resolve, or takes significantly longer to resolve, after an infusion of factor. Several situations might indicate that a child has an inhibitor:

Unresolved bleeds

All HTCs routinely monitor their patients for inhibitors, and many do so more frequently in the first months of treatment. But not every child with hemophilia is seen at an HTC, and older children may go only once a year for their annual comprehensive visit. You may learn that your child has an inhibitor the hard way: when factor no longer works well to stop bleeds. How do you know when factor isn’t working well? If you’re new to hemophilia, this may not be easy—you may not be sure how long it should take a bleed to stop after an infusion. You’re still getting used to identifying symptoms of different bleeds, learning about your child’s individual bleeding pattern, and determining whether a “normal” muscle or joint bleed takes one day or four days to resolve. With so much to learn, it may not immediately dawn on you that the infused factor isn’t working properly, and a bleed is taking much longer than it should to heal. It’s common for parents to think that they simply need to give their child more frequent infusions, or give a higher dose per infusion. Continued bleeding, even with repeated infusions of factor, is the primary way that parents discover their child has an inhibitor.

Increased bruising

Bruising in young children with severe hemophilia is common. But if your child uses factor frequently and you notice increased bruising, this may be a sign of an inhibitor. One mother commented that her doctor noticed increased, repeated bruising at her child’s infusion site, and suspected an inhibitor.

Routine clinic visit

Ideally, you’d like to learn that your child has an inhibitor before an emergency happens and before he gets a major bleed. A blood test at your child’s HTC comprehensive clinic visit can identify an inhibitor. It’s wise to have a child with hemophilia tested for inhibitors routinely: learning that he has an inhibitor in advance of surgery or a major bleed allows parents to have a plan in place and the correct treatment on hand.

Breakthrough bleeds while on prophylaxis

Prophylaxis is the scheduled infusion of factor to help prevent bleeding. Many children with hemophilia on prophylaxis receive factor two to three times a week, enough to keep the lowest level—called the trough level—of factor in the blood above 1%. Children on “prophy” usually will have enough circulating factor to prevent most spontaneous bleeds and abnormal bruising. When a child on prophy starts bruising or even bleeding more often than usual, an inhibitor may be inactivating some of the factor, thus lowering his factor level and increasing his risk of bleeding.

Bleeding after surgery

Because surgery often involves blood loss, it requires special precautions for children with hemophilia. A common first surgery is circumcision. In families with no history of hemophilia, elective circumcision is usually performed soon after birth, and prolonged bleeding that results from the surgery may indicate hemophilia. A blood test will confirm the diagnosis. Depending on the circumcision method, some babies with hemophilia have no bleeding problem with circumcision—even without an

infusion of factor. Others bleed profusely and need factor to control bleeding. Any kind of surgery on a child with hemophilia requires careful planning and monitoring of factor levels, and any child who continues to bleed following surgery, even with adequate factor, should be immediately tested for an inhibitor. Ideally, all children with hemophilia should be tested for an inhibitor before any surgery of any kind.

Allergic reaction following infusion

Inhibitor development in children with hemophilia B is rare—only 1% to 3% of people with hemophilia B get them. Unlike people with hemophilia A and inhibitors, about 45% of people with hemophilia B and inhibitors also develop allergic reactions at about the same time that they develop inhibitors. Allergic reactions may start out mild, and then increase in severity after repeated exposure to products containing factor IX, often to the point of a serious, life-threatening allergic reaction called anaphylaxis. Allergic reactions in hemophilia B patients are not in themselves an inhibitor, but are a sign that an inhibitor has developed.

Later in life

If an inhibitor is going to develop, it will usually do so within twenty exposure days, and almost always before the hundredth exposure day. And the patient will probably have severe hemophilia. Only about 1% to 2% of people with mild hemophilia develop inhibitors. Although most inhibitors occur early in life, in rare cases an inhibitor develops when a child is older, sometimes a teen or an adult. Unlike people with severe hemophilia, people with mild hemophilia who develop inhibitors tend to develop them later in life, usually after intensive exposure to factor during and after surgery or traumatic injury.

Regardless of how you discover your child’s inhibitor, the diagnosis can be both a relief—now you know what’s wrong—and a worry. What will happen next? Your HTC is the best place to turn to for treatments to help manage the inhibitor.