Acquired Inhibitors of Coagulation Factors
GENERAL PRINCIPLES
Acquired inhibitors of coagulation factors may occur de novo (autoantibodies) or may develop in hemophiliacs (alloantibodies) following factor VIII or IX infusions.
Of the acquired inhibitors, those directed against factor VIII occur most commonly. De novo inhibitors often arise in patients who have underlying lymphoproliferative or autoimmune disorders.DIAGNOSIS
Patients who have a factor VIII inhibitor typically present with an abrupt onset of bleeding or bruising, a prolonged aPTT that does not correct after 1:1 mixing with normal plasma, a markedly decreased factor VIII activity, and a normal PT. Patients rarely develop autoantibodies that inhibit other factors (II, V, X) and subsequently prolong aPTT and PT, which do not correct after mixing studies.
TREATMENT
• rFVIIa (NovoSeven) or aPCC, used in a similar manner as for hemophiliacs who have alloantibodies to factor VIII (see Inherited Bleeding Disorders section), treats bleeding problems.
• Recombinant porcine factor VIII (OBI-1) lacks the B domain allowing low cross-reactivity to antiFactor VIII antibodies. In addition, efficacy can be monitored with Factor VIII activity levels in conjunction with clinical evaluation. In an initial trial of patients with acquired hemophilia A, bleeding control was achieved in 86% of patients.47
• Immunosuppression with rituximab,48 prednisone, or prednisolone ± cyclophosphamide49 can eradicate inhibitors.