If you are infusing clotting factor replacement products, you can develop an inhibitor. Health care providers are not completely sure why this happens, but they know certain people are more likely to develop an inhibitor than others.
Each individual has different genetic and treatment-related factors that may make an inhibitor more or less likely. Those factors usually don’t stand alone and can be impacted by other aspects. These are some of the known factors:
Inhibitors occur in 1 out of 10 people with hemophilia A, whereas they happen in 3 out of 100 people with hemophilia B. Therefore, it is more likely for you to develop an inhibitor if you have hemophilia A. While some people with type 3 VWD get an inhibitor, it is substantially less likely to happen than in people with hemophilia A or B.
People with a severe level of their bleeding disorder are more likely to develop an inhibitor than people with a moderate or mild level of severity. Often, people with severe hemophilia will infuse more frequently, especially once they are starting prophylaxis, which increases the exposure to factor replacement products.
People who are black/African American are more likely to develop an inhibitor than people who are white. People who are Asian are more likely to develop an inhibitor than people who are white, but less likely than people who are black/African American. This is possibly due to the genetic mutation causing the bleeding disorder and treatment-related factors.
People who are of Hispanic ethnicity are more likely to develop an inhibitor than people who are non-Hispanic. This is possibly due to the genetic mutation causing the bleeding disorder and treatment-related factors.
People who have a blood relative with a bleeding disorder and inhibitor are more likely to develop an inhibitor themselves in comparison to people, who do not have a blood relative with a bleeding disorder and inhibitor. This is possibly due to the genetic mutation causing the bleeding disorder.
Some inheritable bleeding disorders are caused by variations in genes. For people with hemophilia A, people with certain genetic variations appear to be more prone to develop an inhibitor in comparison to others. A person with hemophilia A caused by a large deletion genetic variation (removal of an entire gene, several genes, or a section of the chromosome) is more likely to develop an inhibitor than a somebody with a nonsense genetic variation (change in one DNA part leading to an early signal to stop building a protein). On the other hand, a person with a missense genetic variation (change in one DNA part leading to the wrong amino acid being included in the protein) is less likely to develop an inhibitor than a person with a nonsense genetic variation.
The impact of genetic variations on the development of inhibitors in other bleeding disorders is currently unclear.
For more information about genetic mutations, please visit the National Human Genome Research Institute.
Most often inhibitors develop during the first 50 treatments with clotting factor replacement products. During this time it is more likely for your body to see the treatment as a foreign body, which will lead to the inhibitor response. The likelihood of developing an inhibitor decreases with the number of infusions. After 150 infusions it is substantially less likely that a person would develop an inhibitor, but it can still happen. Also, people with a high frequency of factor replacement infusions, for example in response to surgery, are at a higher risk of inhibitor development than people who are on a standard prophylaxis treatment regime.