(Level 4) [[63, 68]] Porcine factor VIII prepared from the plasma of pigs has been effective in halting bleeding in some patients. The plasma-derived preparation is being superceded by a recombinant porcine factor VIII concentrate currently in clinical trials. With an inhibitor level ≥5 BU, the likelihood is low that specific factor replacement FDA approved Drug Library cost will be effective in overwhelming the inhibitor without ultra high dose continuous infusion therapy. Alternative agents include bypassing agents such as recombinant factor VIIa (rFVIIa)

and prothrombin complex concentrates (PCC), including the activated forms (APCC). The efficacy of two doses of rFVIIa and one dose of APCC for management of joint bleeding has been shown to be essentially equivalent. (Level 2) [[69]] Notably, however, some patients respond better to one agent than the other, highlighting the need to individualize therapy. (Level 2) [[69, 70]] An

anamnestic immune response should be expected in patients with hemophilia Sirolimus B and a FIX inhibitor treated with prothrombin complex concentrates––whether activated or not––since these concentrates all contain FIX. On the other hand, the risk of anamnesis in patients with hemophilia A and an inhibitor treated with a(n) (activated) prothrombin complex concentrate will vary depending on the concentrate and its content of FVIII, which is generally minimal. It is estimated that APCC leads to an anamnestic response in approximately 30% of FVIII inhibitor patients. Although there has been interest in the use of immunosuppressive therapies in patients with inhibitors, their role is not yet defined, and

there is no consensus as to whether they have a place in the management of these patients. Up to 50% of hemophilia B patients with inhibitors may have severe allergic reactions, including anaphylaxis, to FIX administration. Such reactions can be the first symptom of inhibitor development. Newly diagnosed hemophilia B patients, particularly those with a family history and/or with genetic defects predisposed to inhibitor development, should be treated in a clinic or hospital 上海皓元 setting capable of treating severe allergic reactions during the initial 10–20 treatments with FIX concentrates. Reactions can occur later, but may be less severe. (Level 4) [[71, 72]] In patients with severe hemophilia A, eradication of inhibitors is often possible by immune tolerance induction (ITI) therapy. (Level 2) [[73, 74]] Before ITI therapy, high-responding patients should avoid FVIII products to allow inhibitor titers to fall and to avoid persistent anamnestic rise. As noted, some patients may develop an anamnestic response to the inactive FVIII molecules in APCC as well. (Level 2) [[75]] Optimal regimen (product or dose) for ITI remains to be defined.