Healthcare professionals face major therapeutic challenges when hemophilic patients develop inhibitors or antibodies that develop following replacement therapy.
The incidence of hemophilia is estimated to be 1:10,000 live male births. While an X-linked disorder, as many as 1/3 of new cases may have been caused from a spontaneous mutation. Within this population, inhibitors develop in approximately 15% to 30% of patients with hemophilia A and in 2% to 5% of patients with hemophilia B. These antibodies are alloimmune. Development of inhibitors may also occur in previously normal (nonhemophilic individuals) and is called acquired hemophilia. These antibodies are autoimmune. The kinetics of inhibitors vary between alloimmune and autoimmune; Type 1 kinetics with rapid binding and removal of the replacement coagulation factor representing those most commonly seen in hemophilia or alloimmune antibodies, and Type 2 kinetics seen in autoimmune antibodies or acquired hemophilia. Alloimmune antibodies in hemophilia are most commonly IgG immunoglobulins, most commonly subtype 1 and 4.