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

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Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study. / Türkantoz, Halet; Königs, Christoph; Knöbl, Paul; Klamroth, Robert; Holstein, Katharina; Huth-Kühne, Angela; Heinz, Jürgen; Eichler, Hermann; Tiede, Andreas.

In: J THROMB HAEMOST, Vol. 18, No. 1, 01.2020, p. 36-43.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Türkantoz, H, Königs, C, Knöbl, P, Klamroth, R, Holstein, K, Huth-Kühne, A, Heinz, J, Eichler, H & Tiede, A 2020, 'Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study', J THROMB HAEMOST, vol. 18, no. 1, pp. 36-43. https://doi.org/10.1111/jth.14618

APA

Türkantoz, H., Königs, C., Knöbl, P., Klamroth, R., Holstein, K., Huth-Kühne, A., Heinz, J., Eichler, H., & Tiede, A. (2020). Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study. J THROMB HAEMOST, 18(1), 36-43. https://doi.org/10.1111/jth.14618

Vancouver

Türkantoz H, Königs C, Knöbl P, Klamroth R, Holstein K, Huth-Kühne A et al. 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. https://doi.org/10.1111/jth.14618

Bibtex

@article{d8cc3ddd6dae4616911744670b299260,
title = "Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study",
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.",
author = "Halet T{\"u}rkantoz and Christoph K{\"o}nigs and Paul Kn{\"o}bl and Robert Klamroth and Katharina Holstein and Angela Huth-K{\"u}hne and J{\"u}rgen Heinz and Hermann Eichler and Andreas Tiede",
note = "{\textcopyright} 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of InternationalSociety on Thrombosis and Haemostasis.",
year = "2020",
month = jan,
doi = "10.1111/jth.14618",
language = "English",
volume = "18",
pages = "36--43",
journal = "J THROMB HAEMOST",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: Data from the GTH-AH 01/2010 Study

AU - Türkantoz, Halet

AU - Königs, Christoph

AU - Knöbl, Paul

AU - Klamroth, Robert

AU - Holstein, Katharina

AU - Huth-Kühne, Angela

AU - Heinz, Jürgen

AU - Eichler, Hermann

AU - Tiede, Andreas

N1 - © 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of InternationalSociety on Thrombosis and Haemostasis.

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

U2 - 10.1111/jth.14618

DO - 10.1111/jth.14618

M3 - SCORING: Journal article

C2 - 31448877

VL - 18

SP - 36

EP - 43

JO - J THROMB HAEMOST

JF - J THROMB HAEMOST

SN - 1538-7933

IS - 1

ER -