Immune Tolerance Induction (ITI) in Hemophilia A and Inhibitors using VWF Containing Factor VIII Concentrates.

Immune tolerance induction using the Bonn protocol (ITI) is the most successful approach to eliminate inhibitors in hemophilia A patients. The influence of the type of concentrate, particularly the content of von-Willebrand-Factor (VWF) used for ITI is under discussion and has never been investigated comparatively.

A longitudinal study at the Frankfurt center on the influence of VWF on ITI using the Bonn protocol (low responder: 50–100 IU FVIII/kg bw daily or every other day; high responder: 100–150 IU FVIII/kg bw every 12 hours; according to the bleeding tendency concomitant treatment with FEIBA®/Baxter) showed a significantly decreased success rate since the introduction of high purity plasma derived (pd) and recombinant (rec) F VIII products (success rate with pd VWF-F VIII 91% vs ultrapure F VIII 29%). Similar observations have been reported by the Bonn and Bremen centers (success rate with pd VWF-F VIII 87% vs ultrapure F VIII 54%). A meta-analysis of different ITI studies revealed a higher success rate with the use of VWF-FVIII concentrates (88% using VWF-FVIII and 63% using rec and pd/monoclonal purified F VIII).

The change to VWF-FVIII concentrates during ITI in inhibitor patients who showed an unsatisfactory treatment course with ultrapure F VIII concentrates (n=12 high responders) led to success in 10 out of 12 patients after a median treatment period of 17 months (5–36 months). Successful IT after changing to VWF-F VIII concentrates was evaluated by a questionnaire in another 10 high responders who had unsatisfactory treatment courses with ultrapure F VIII concentrates.

These observations indicate that VWF has a major impact on the success of ITI.