Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study

J Thromb Haemost. 2020 Jan;18(1):36-43. doi: 10.1111/jth.14618. Epub 2019 Sep 12.


Background: Recombinant porcine factor VIII (rpFVIII, OBI-1, susoctocog alfa) is used for the treatment of acute bleeds in patients with acquired hemophilia A (AHA). Inhibitors in AHA can sometimes cross-react with rpFVIII.

Objectives: To assess the frequency, strength, and determinants of cross-reactivity.

Patients/methods: Baseline samples from 70 patients of the prospective, observational cohort study GTH-AH 01/2010 were assessed for anti-human FVIII and anti-rpFVIII inhibitors using modified Nijmegen-Bethesda assays, as well as anti-human FVIII domain reactivity using enzyme-linked immunoassay (ELISA).

Results: Anti-human FVIII inhibitors were present in all samples ranging between 0.7 and 3891 Bethesda Units (BU)/mL. Inhibitors from 31 of 70 patients (44%) partially inhibited rpFVIII with anti-rpFVIII titers ranging between 0.5 and 471 BU/mL. Anti-rpFVIII titers were ≤5 BU in most patients. Patients with cross-reacting inhibitors, as compared to patients without, had significantly higher anti-human FVIII titers (27.8 versus 5.4 BU/mL) and lower baseline FVIII activity (<1 versus 2.6 IU/dL). The ratio between anti-rpFVIII to anti-human titers was highest for inhibitors involving the C1 domain. Cross-reactivity was very rare, if inhibitors reacted only with the C2 domain of FVIII (6%). An anti-human FVIII titer of >100 BU/mL predicted cross-reactivity with 97% likelihood, whereas an anti-human FVIII titer of <3.8 BU/mL predicted absent cross-reactivity with 90% likelihood.

Conclusion: Cross-reacting inhibitors should be considered when choosing a treatment for bleeding patients with AHA. Cross-reactivity is frequent in patients with anti-human FVIII titers of >100 BU/mL.

Keywords: acquired hemophilia; bleeding; inhibitor; porcine factor VIII; susoctocog alfa.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation Tests
  • Cross Reactions
  • Factor VIII*
  • Hemophilia A* / diagnosis
  • Hemophilia A* / drug therapy
  • Humans
  • Prospective Studies
  • Swine


  • Factor VIII