Why Some Patients Develop Inhibitors
Individuals with a severe factor deficiency (FVIII or FIX levels at <0.01 U/mL) have the highest risk of developing inhibitors. Risk factors for inhibitor development include race, with blacks and Hispanics having increased risk; severity of hemophilia, severe being at highest risk; genetic defect, with defects such as large deletions being higher; and family history of inhibitor also increasing the risk. Other factors such as presence of inflammatory states, age at first infusion, intervals between exposures etc., have been suggested but remain unproven.
The immunologic mechanisms regulating inhibitor development are not fully known, but it is clear that certain patients may have traits that put them at higher risk for developing one inhibitor more than another.
There is some evidence that histocompatibility class II gene products, the type of mutation causing the hemophilia, as well as defective functioning of some immunosuppressor mechanisms, can all contribute to the development of inhibitors.