Halet Türkantoz1, Christoph Königs2, Paul Knöbl3, Robert Klamroth4, Katharina Holstein5, Angela Huth-Kühne6, Jürgen Heinz7, Hermann Eichler8, Andreas Tiede1. 1. Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 2. Department of Pediatrics, Clinical and Molecular Hemostasis, University Hospital, Goethe University, Frankfurt am Main, Germany. 3. Hematology and Hemostasis, Vienna Medical University, Vienna, Austria. 4. Internal Medicine, Vivantes Clinic Friedrichshain, Berlin, Germany. 5. Hematology and Clinical Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6. Hemophilia Care Center, SRH Kurpfalzkrankenhaus Heidelberg, Heidelberg, Germany. 7. Hematology and Oncology, Freiburg University Hospital, Freiburg, Germany. 8. Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University and Saarland University Hospital, Homburg/Saar, Germany.
Abstract
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.
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-humanFVIII and anti-rpFVIII inhibitors using modified Nijmegen-Bethesda assays, as well as anti-humanFVIII domain reactivity using enzyme-linked immunoassay (ELISA). RESULTS: Anti-humanFVIII 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-humanFVIII 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-humanFVIII titer of >100 BU/mL predicted cross-reactivity with 97% likelihood, whereas an anti-humanFVIII 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 bleedingpatients with AHA. Cross-reactivity is frequent in patients with anti-humanFVIII titers of >100 BU/mL.
Authors: Claude Négrier; Johannes Oldenburg; Gili Kenet; Shannon L Meeks; Jean-Claude Bordet; Jens Müller; Sandra Le Quellec; Peter L Turecek; Nikola Tripkovic; Yesim Dargaud Journal: Res Pract Thromb Haemost Date: 2022-06-19
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Authors: Andreas Tiede; Peter Collins; Paul Knoebl; Jerome Teitel; Craig Kessler; Midori Shima; Giovanni Di Minno; Roseline d'Oiron; Peter Salaj; Victor Jiménez-Yuste; Angela Huth-Kühne; Paul Giangrande Journal: Haematologica Date: 2020-05-07 Impact factor: 9.941