Acquired Inhibitors Against Factor VIII and Factor IX

Summary

Patients with spontaneously acquired factor VIII and factor IX inhibitors generally have a severe, diffuse bleeding diathesis. These inhibitors occur with equal frequency in men and women and are most common in the ranges of 20–30 and 60–80 years of age. The hemorrhagic diathesis is usually manifested by cutaneous and muscular bleeding, intra- and postoperative bleeding, and intraabdominal hemorrhage. Hemarthrosis is far less common than in patients with therapy-induced isoantibodies. The underlying disease may be an autoimmune disorder or a solid neoplasm. Postpartum inhibitors and drug-induced autoantibodies are usually transient but may cause a severe bleeding diathesis. Diagnosis starts with the PTT, and abnormal mixing tests in the PTT screen can suggest the presence of an inhibitor-associated hemorrhagic disorder. The diagnosis is established by the Bethesda assay. The autoantibodies are distinguished from the therapy-induced inhibitors in hemophilia by their complex kinetics. The mortality rate is very high, ranging from 20% to 30%. The first treatment priority is the control of bleeding. This can be accomplished with activated PCC (Feiba), porcine factor VIII (Hyate C), or recombinant factor VIIa. Experimental therapies for antibody elimination involve the use of γ-globulins and/or immunosuppressant therapy.

Acquired antibodies against coagulation factors can occur in healthy individuals as well as in patients with underlying diseases. As a rule, spontaneously acquired inhibitors to factors VIII and IX are associated with severe, life-threatening hemorrhage. The autoantibodies differ from the therapeutically induced isoantibodies in hemophilia both in their kinetics and in their clinical manifestations.