Inhibitor antibodies to factor VIII and factor IX: Management

Inhibitor antibodies directed against factor VIII or factor IX present chal lenges to the clinician. Fortunately, several management options are availa ble, although each has disadvantages as well as advantages. Alloantibodies against factor VIII (which develop in 25 to 50% of children with severe hem ophilia A, as well as in a small percentage of children with mild or modera te hemophilia A) may be low titer and transient or may be high titer. Most patients with high-titer problematic inhibitors now try to eliminate the in hibitor by using one of several immune tolerance induction (ITI) regimens. For treatment of bleeding episodes in patients who have high-titer (greater than or equal to 5 Bethesda units) inhibitors, one can use a prothrombin c omplex concentrate (PCC) (preferably an activated PCC [APCC]), recombinant (r) factor VIIa, or porcine factor VIII. The choice of product is generally dependent on the type and severity of the patient's bleeding, degree of cr oss-reactivity of the patient's inhibitor with porcine factor VIII, physici an familiarity with the product, product availability, and cost. In persons with hemophilia B, alloantibodies occur in only 1 to 3% of sever ely affected individuals. However, in roughly half of those who develop inh ibitors, anaphylaxis or severe allergic reactions occur on infusion of any type of factor IX-containing product. This phenomenon usually develops afte r relatively few exposures to factor IX; thus it is recommended that the fi rst 10 to 20 infusions of factor IX given to children with severe hemophili a B be given in a setting equipped for treatment of shock. For treatment of bleeding episodes in patients with severe allergic reactions, rF VIIa is t he treatment of choice. ITI has been less successful in hemophilia B patien ts with inhibitors than in those with hemophilia A, and in a subgroup of pa tients with severe allergic reactions who were desensitized to factor IX an d then tried on ITI, results were even poorer. Additionally, several develo ped nephrotic syndrome while on ITI. For hemophilia B patients with inhibit ors who do not have allergic reactions to factor IX, bleeding episodes can be treated with PCC or APCC or with rF VIIa. Autoantibodies directed against factor VIII are rare but can occur in a var iety of settings. They occur mainly in adults, and bleeding is often severe and life threatening. Although some factor VIII autoantibodies disappear s pontaneously, most require immunosuppression. Corticosteroids and cyclophos phamide are generally recommended. For treatment of bleeding, therapeutic o ptions include (human) factor VIII concentrates, porcine factor VIII, APCC, and rFVIIa. The choice of product is generally determined by the consultin g hematologist's familiarity with the product, product availability and cos t, as well as response to treatment.