Understanding hemophilia treatment options if you have inhibitors
Fact-checked by Some people taking standard therapies for the bleeding disorder hemophilia will develop inhibitors. Inhibitors are antibodies that can reduce treatment effectiveness. While this can be a stressful aspect of the hemophilia treatment journey, there are options to control and prevent bleeds after hemophilia inhibitor formation.
People with hemophilia lack certain blood-clotting proteins, or clotting factors, leading to symptoms of excessive and prolonged bleeding. The standard treatment approach is factor replacement therapy, which provides the body with a working version of the missing clotting factor.
Sometimes, the immune system recognizes the supplied clotting factor as a harmful invader and develops antibodies to block its activity. These neutralizing antibodies are known as inhibitors. Occurring in up to 30% of people with severe hemophilia A and less than 5% of those with hemophilia B, inhibitors are a major reason why factor treatment stops working for some people.
If not properly managed, inhibitors can leave patients at risk of serious bleeding complications. Understanding the treatment options for patients with inhibitors will help ensure they maintain the best possible bleed control and quality of life.
How inhibitors are diagnosed and monitored
The presence of inhibitors and their level (titer) can be identified with a simple blood test. When inhibitors are found, they may be classified as high-titer (higher levels) or low-titer (lower levels).
Experts recommend, at a minimum, once yearly inhibitor testing for most patients on factor replacement therapies. More frequent testing is recommended:
- when first starting treatment (once every three to six months for the first 150 doses)
- before and after switching factor products
- before elective invasive procedures
- after intensive treatment or surgery
Providers should test for inhibitors whenever the response to replacement therapy is suboptimal, such as when clotting factor levels are lower than expected or when bleeds occur more frequently.
After an inhibitor diagnosis, patients should speak with their healthcare providers about hemophilia inhibitor management. Their hemophilia inhibitor care plan will likely include medication changes to help ensure bleeds are effectively controlled.
While living with hemophilia and inhibitors, patients will also likely undergo regular blood tests to monitor inhibitor titers and treatment efficacy.
Bypassing agents
Bypassing agents for hemophilia are an alternative to factor replacement therapy. They are most often used on-demand to manage active bleeding, but can also be used prophylactically to prevent bleeding in some cases.
There are two types of approved bypassing agents:
- recombinant activated factor VII (rFVIIa)
- activated prothrombin complex concentrate (aPCC)
Rather than supplying a working version of the required clotting factor, these medications activate other steps in the clotting process, essentially enabling bleed control without the need for the clotting factor that the inhibitors are targeting.
Nonfactor therapies for hemophilia with inhibitors
Another alternative treatment approach for people with inhibitors is nonfactor therapy for hemophilia, which is usually used prophylactically to prevent bleeding.
Like bypassing agents, nonfactor therapies don’t replace missing or dysfunctional clotting factors; instead, they promote clotting in other ways. Nonfactor therapies typically work in one of two ways:
- factor mimicking: work in a similar way to the missing clotting factor to replace its function
- rebalancing: work to reduce natural processes that regulate or inhibit clotting
Immune tolerance induction (ITI)
Immune tolerance induction therapy, or ITI, is a therapeutic approach that aims to re-educate the immune system to reduce inhibitor production. It is often recommended for treating hemophilia with inhibitors because, if successful, patients can continue with standard factor replacement therapies.
The specific ITI protocol can vary, but it typically involves administration of a replacement therapy as frequently as twice daily. It is sometimes given alongside a bypassing agent or medications to suppress the immune system. ITI may be stopped once inhibitors are eliminated and the response to replacement therapies is good, which could take months or years.
ITI is successful in about 60% to 80% of people with hemophilia A and 50% or less of those with hemophilia B. Various factors can influence whether ITI will be successful, including:
- inhibitor titer: lower inhibitor titer at the start of treatment and lower peak titer are associated with a higher chance of success
- length of exposure to factor replacement: people who develop inhibitors later in factor replacement treatment often have better outcomes
- ethnicity: Hispanic or Latino ethnicity may be associated with a lower success rate
- genetic variant: some disease-causing genetic mutations may affect the outcomes of ITI
Managing breakthrough bleeds and emergencies
Even with preventive therapies and ITI, breakthrough bleeds with inhibitors are still possible and should be treated immediately. The preferred method for treating bleeding with inhibitors is bypassing agents, which may be repeatedly administered until bleeding is under control.
Recombinant activated factor VII products are the preferred first-line treatment in these emergency situations. While aPCC is also an option, it can lead to serious complications in people using certain prophylactic therapies.
In cases of severe and life-threatening bleeding, plasmapheresis may be used to quickly manage the crisis. This is a blood-filtering procedure that helps remove inhibitors from the blood.
Treatment considerations for children vs. adults
Inhibitors can develop at any time, but are most often detected in younger children with severe hemophilia. Diagnosing and treating hemophilia inhibitors in children involves a process similar to that in adults, but there are some unique treatment considerations for young patients.
As in adults, bleeding control and prevention for a child with inhibitors may involve bypassing agents and nonfactor therapies, but the following considerations must be made:
- some specific medications are not approved for use in children younger than 12
- children may need higher doses or more frequent administration of certain medications than adults because they’re cleared from the body more quickly
ITI is also commonly used in children. In a small study of pediatric and adult patients with high-titer hemophilia A inhibitors undergoing ITI, treatment was started, on average, more quickly in children than in adults. Children also had higher treatment success rates than adults, and successful ITI took less time on average in children.
Treatment priorities may also vary with age. If a child is very young, they may not be involved in many activities yet. The focus of their treatment is to prevent serious bleeds and preserve healthy joints. As children grow, a major treatment goal may be to preserve their ability to participate in physical and social activities.
Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
