Diagnosis:
Hemophilia A inhibitor
• An alloantibody against factor VIII should be considered when an appropriate dose of factor VIII is administered but the desired increase in factor activity is not reached.
• Anti–factor VIII antibodies can be detected on coagulation studies by performing a mixing study. A mixing study is performed by mixing one volume of patient plasma with one volume of pooled normal plasma. If a factor deficiency is present, the pooled normal plasma will correct the prolonged activated partial thromboplastin time (aPTT). However, the presence of an alloantibody will inhibit the factor VIII in both the patient plasma and the pooled normal plasma.
• Lupus anticoagulants (LACs) can also inhibit coagulation by interfering with the phospholipid surfaces that coagulation factors require for their activity. However, the inhibitor activity is usually seen upon immediate mixing and with incubation. In addition, LACs are more likely to cause thrombosis, not bleeding.
• Anti–factor VIII alloantibodies are generally weaker antibodies than LACs, and with incubation, their inhibition will strengthen. Therefore, the immediate mix may correct, and then with incubation for 1 to 2 hours, the aPTT will prolong as the antibody’s binding is enhanced.
• The strength of an antibody should be determined using a Bethesda assay, which measures the titer of the antibody. The higher the Bethesda units (BUs), the greater the strength of the antibody. A BU reflects the amount of inhibitor that will inactivate half of the factor activity.
• If there are fewer than 5 BUs, then overwhelming the inhibitor with increasing factor replacement can be attempted (i.e., give a very large dose of factor VIII). However, if there are more than 5 BUs, then alternate concentrates (e.g., porcine factor VIII) or bypassing agents (e.g., factor VIII inhibitor bypassing activity, prothrombin complex concentrates, recombinant factor VIIa) should be used to treat active bleeding.
