Treating “bleeds” when inhibitors are present takes into account two things: the titer (the amount of inhibitors) and the anamnestic response (the strength) of the immune response. Some of the options available to treat bleeds in people with inhibitors include:

High doses of factor

Bleeds in “low responders” may be treated with higher doses of factor concentrate. This is not effective in people with high titer inhibitors because it is not feasible to infuse a large or frequent enough to overcome the strength of the inhibitor antibody.

Bypassing agents

To form a stable clot, multiple proteins must work together. These proteins are called “clotting factors” and they activate each other one after the other.  The end result is fibrin, which forms a net to stabilize the clot.  If one of the clotting factors is missing, the sequence is interrupted.  That means you have a weak clot that will break apart because the fibrin net wasn’t formed to help hold it together.  This process is called the coagulation cascade. (See here for a brief description of the coagulation cascade.) In short, factor VIII and factor IX eventually trigger the production of factor VIIa to continue the coagulation process and form a clot. Since people with inhibitors cannot replace the missing factor VIII or factor IX (because the antibodies destroy it), they must use a different product called bypassing agents. These products “bypass” the factors that are blocked by the inhibitor to continue the cascade and help form a clot.

Porcine factor VIII

The original plasma porcine factor VIII was made from pig plasma and was similar to the human factor VIII and was effective in treating bleeds in people with inhibitors. This product was discontinued in 2004. A new recombinant porcine factor VIII was approved for use in adults with acquired hemophilia A, but not congenital hemophilia A. This product has been used in congenital FVIII patients with inhibitors and found to be effective, but is not yet FDA-approved for this indication, although it has been accepted for publication.

Is Prophylaxis an Option for Those with Inhibitors?

Currently, one bypassing agent for those with inhibitors is FDA approved for prophylaxis. Concerns about prophylaxis for inhibitor patients include the cost of treatment, volume and length of infusion time, the short-half life, the burden of treatment, and the risk of thrombosis.

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