Inhibitors

People with hemophilia have a higher quality of life today than ever before, but complications can still occur. Approximately 15-20% of people with hemophilia will develop an  antibody—called an inhibitor—to the product used to treat or prevent bleeding episodes. Developing an inhibitor is one of the most serious and costly complications of hemophilia.

About Inhibitors

People with hemophilia use treatment products called clotting factor concentrates. This treatment improves blood clotting and is used to stop or prevent a bleeding episode. Inhibitors develop when the body’s immune system stops accepting the factor (factor VIII for hemophilia A and factor IX for hemophilia B) as a normal part of blood. The body thinks the factor is a foreign substance and tries to destroy it using inhibitors. The inhibitors stop the factor from working. This makes it more difficult to stop a bleeding episode. People with hemophilia who develop an inhibitor do not respond as well to treatment. Inhibitors most often appear during the first year of treatment but they can appear at any time.

Cost of Care

Caring for people with inhibitors poses a special challenge. The health care costs associated with inhibitors can be staggering because of the cost and amount of treatment product required to stop bleeding. Also, people with hemophilia who develop an inhibitor are twice as likely to be hospitalized for a bleeding complication.

Risk Factors and Causes

Scientists do not know exactly what causes inhibitors. Risk factors that have been shown in some studies to possibly play a role include:

·         Age

·         Race/ethnicity

·         Type of hemophilia gene defect

·         Frequency and amount of treatment (inhibitors typically occur within the first 50 times factor is used)

·         Family history of inhibitors

·         Type of factor treatment product

·         Presence of other immune disorders

Diagnosis

A blood test is used to diagnose inhibitors. The blood test measures inhibitor levels (called inhibitor titers) in the blood. The amount of inhibitor titers is measured in Bethesda units (BU). The higher the number of Bethesda units, the more inhibitor is present. “Low titer” inhibitor has a very low measurement, usually less than 5 BU. “High titer” inhibitor has a very high measurement, usually much higher than 5 BU.

Inhibitors are also labeled “low responding” or “high responding” based on how strongly a person’s immune system reacts or responds to repeated exposure to factor concentrate. When people with high-responding inhibitors receive factor concentrates, the inhibitor titer measurement increases quickly. The increased inhibitor titer prevents the clotting factor concentrates from stopping or preventing a bleeding episode. Repeated exposure to clotting factor concentrates will cause more inhibitors to develop.

When people with low-responding inhibitors receive factor concentrates, the inhibitor titers do not rise. Therefore, people with low-responding inhibitors can usually still use clotting factor concentrates to stop or prevent a bleeding episode.
 

Treatment

Treating people who have inhibitors is complex and remains one of the biggest challenges in hemophilia care today. If possible, a person with inhibitors should be cared for at a hemophilia treatment center (HTC). HTCs are specialized health care centers that bring together a team of doctors, nurses, and other health professionals experienced in treating people with hemophilia.

Some treatments for people with inhibitors include the following:

·         High-Dose Clotting Factor Concentrates: People who have low responding inhibitors may be treated with higher amounts of factor concentrate to overcome the inhibitor and yet have enough left over to form a clot. It is important to test the blood and measure the factor level after this new treatment schedule is established to see if the inhibitor is gone.

·         Bypassing Agents: Special blood products are used to treat bleeding in people with high titer inhibitors. They are called bypassing agents. Instead of replacing the missing factor, they go around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot. People taking bypassing agents should be monitored closely to make sure the blood is not clotting too much or clotting in the wrong place in the body.

·         Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from happening in the blood and to teach the body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor concentrates every day for many weeks or months.

ITI therapy requires specialized medical expertise, is costly, and may take a long time to work. In many cases, ITI gets rid of the inhibitor. However, patients may need to continue taking frequent, large amounts of factor concentrates for many years to keep the inhibitor from coming back. HTCs can serve a vital role in supporting patients who undergo a treatment regimen as intensive as ITI.

CDC Research

CDC is interested in learning more about why some people develop inhibitors and how they could be prevented. The Inhibitor Project began in 2005 and was implemented to explore the following questions:

·         Does a change in treatment products (from one type of factor product to another) lead to an inhibitor?

·         Are people with specific gene mutations more likely to develop an inhibitor?

·         What characteristics make some people more likely to develop an inhibitor than others?

·         Why do some people develop inhibitors and others do not?

·         How often do inhibitors occur?

In the Inhibitor Project, a limited number of federally funded hemophilia treatment centers across the United States enroll study participants who have hemophilia A or hemophilia B. Detailed information about their hemophilia, their complications, and their treatment is collected and studied over time. The CDC laboratory tests each participant’s blood and determines if he or she has an inhibitor. Testing all of the blood at the CDC laboratory, rather than using several different labs throughout the country, ensures that the testing procedures are consistent and reliable for analysis. The blood samples are also used to study hemophilia-related genes and gene mutations to learn more about who is more likely to develop an inhibitor even before treatment is started. The laboratory results are shared with the study participant’s physician.

Through additional research, we hope to increase our understanding of inhibitors. Knowing more about why some people develop inhibitors and others do not may help us predict who will develop an inhibitor before treatment is started. This may lead to a decreased rate of inhibitors, decreased health care costs, and the licensure of safe and more effective treatment products for people with hemophilia.

Did You Know?

When people are being treated for an inhibitor, they receive frequent, large amounts of clotting factor concentrates and therefore may need a central venous access device (CVAD). A CVAD is a small tube placed in a vein. It can stay in the vein for a long time. Clotting factor concentrates can be given through the CVAD instead of by injection or infusion through a painful needle stick. A downside of having a CVAD is that people with CVADs are more likely to develop infections, blood clots, and other complications than those without CVADs. It is important for people with hemophilia and their caregivers to learn how to care for the device.

Source : http://www.cdc.gov/ncbddd/hemophilia/inhibitors.html