A person may not always have clear symptoms associated with the presence of an inhibitor. In cases where individuals are symptomatic, an inhibitor is usually suspected when bleeding does not stop even after treatment doses.
Once an inhibitor is suspected, the only way to confirm a case is through laboratory testing during a regular physician visit. Confirmation is made using a blood test called the “Bethesda (inhibitor) assay.” This test measures the presence and amount of antibodies directed against a coagulation factor in a person's blood after being exposed to factor.
If the results of the Bethesda assay are positive, it means that there is a detectable level of antibodies working against the deficient coagulation factor being produced as a result of being treated with factor. The degree to which this affects a person is measured in "units." Inhibitors are classified into two categories based upon unit levels achieved. Those with a ‘5 or higher’ Bethesda units test result are classified as having a "high-responding" inhibitor level; those who measure ‘below 5 Bethesda units’ despite repeated exposure to factor concentrate, are classified as having a "low-responding" inhibitor level.
People with ‘high-responding’ inhibitor levels often have quick and strong immune system responses directed against Factor (VIII or IX), meaning that the inhibitor level can increase to very high levels of antibodies.
In cases where a person has a ‘low-responding’ inhibitor level, the body's immune response to factor is slow—and it produces a persistently low level of antibodies despite the person's continual exposure to factor concentrate.
A positive test result does not mean a person will always have an inhibitor. Treatments may work to keep the inhibitor in check. In certain cases, inhibitor levels may drop over a period of months to years, to an undetectable range. Some inhibitors may reappear with further exposure, often months later. These cases are often a special type of ‘low-responding’ inhibitor cases, classified as ‘transient’ inhibitors.
Inhibitors pose a very challenging medical complication because of the uncertainty of how they can spontaneously disappear, respond to various treatments or in other cases require ongoing management for years.
Copyright National Hemophilia Foundation
Last Updated May 2022