Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study
Beteiligte Einrichtungen
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.
Bibliografische Daten
Originalsprache | Englisch |
---|---|
ISSN | 1538-7933 |
DOIs | |
Status | Veröffentlicht - 01.2020 |
Anmerkungen des Dekanats
© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of InternationalSociety on Thrombosis and Haemostasis.
PubMed | 31448877 |
---|