Researchers have discovered that plasma-derived factor VIII/von Willebrand factor (FVIII/VWF) complex demonstrates greater protection against the formation of inhibitors than isolated FVIII in patients with hemophilia, as published in Haemophilia.

One of the most severe complications of FVIII replacement therapy is the formation of neutralizing autoantibodies. Studies show that around 1 in 4 patients with hemophilia experience this complication. The unintended formation of inhibitors in FVIII replacement therapy imposes a significant burden on patients, both physiologically and in terms of additional healthcare costs.

Studies have suggested that different commercial FVIII preparations influence whether inhibitors are formed. Although the underlying mechanisms of this phenomenon remain a mystery, it appears that concentrates containing native plasma-derived FVIII/VWF complexes offer greater protection against inhibitors than complexes produced by the combination of isolated proteins in a laboratory setting.

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The authors of the study set out to evaluate whether plasma-derived FVIII/VWF complexes indeed offer better protection against the formation of inhibitors compared to recombinant FVIII products. To carry out their study, they used FVIII deficient mouse models for in vivo studies and plasma samples from patients with hemophilia A for ex vivo studies. Both mouse models and plasma samples were infused with different FVIII products, and inhibitor activities were later determined.

The results demonstrated that in hemophilia A mouse models preinfused with inhibitors, VWF-containing FVIII concentrate was more effective in restoring circulating levels of FVIII compared to concentrates composed of isolated FVIII. As for the plasma samples from patients with hemophilia A, plasma-derived FVIII/VWF complexes were more effective in offering protection against inhibitors compared to recombinant FVIII concentrates.

“Our results reveal intrinsic differences in the neutralizing effects of FVIII inhibitors against various FVIII concentrates in an animal model and in plasma from [hemophilia A] patients treated with various FVIII products,” the authors concluded.


Bravo MI, Pérez A, Raventós A, et al. Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: a translational studyHaemophilia. Published online June 2, 2022. doi:10.1111/hae.14589