Factor VIII Inhibitoren


Synonym Antibodies 

Alloantibodies of different immonoglobulin categories Autoantibodies

Incidence 5 - 52 % in patients with hemophilia A

Clinical Significance

A complication of factor VIII replacement therapy is the development of alloantibodies that inhibit factor VIII activity. The formation is triggered by a neoantigen formation of the substituted factor, gene defects or vaccinations at the beginning of therapy. The alloantibodies usually occur within 20 days of exposure. This neutralizes factor VIII, leading to massive bleeding complications.
True autoantibodies against factor VIII are very rare and exhibit second-order inhibition kinetics.


  • Bleeding complications despite theoretically adequate substitution
  • Determination of the inhibitor titer (Bethesda units)
  • The type of therapy (e.g. immune tolerance therapy, Bonner protocol) depends on the titer of the factor VIII inhibitors
  • The therapy as well as the selection of the blood components and plasma derivatives is dependent on the classification in low and high responders:
                                  Low responder: < 5 Bethesda Units
                                  High responder: > 5 Bethesda Units


  1. Rosen S et al. Clinical application of a chromogenic substrate method for determination of factor VIII activity. Thromb Haemost 54, 818-823, 1985.
  2. Barnett B, Kruse-Jarres R, Leissinger CA. Current management of acquired factor VIII inhibitors.  15(5):451-5, 2008
  3. Astermark J. FVIII inhibitors: pathogenesis and avoidance Blood  125:2045-205, 2015.
  4. Wittmer, C, Young G. F VIII Inhibitors in Hemophilia A: rationale and latest evidence. Ther. Adv. Hematol. 4: 59-72, 2013.
Test kits
Inhibitor Assays

Factor VIII Inhibitor Kit

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Factor VIII Inhibitor Kit HCV negative

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