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International Recommendations on the Diagnosis and Treatment of Acquired Hemophilia A

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Tiede, Andreas, Collins, Peter, Knoebl, Paul, Teitel, Jerome, Kessler, Craig, Shima, Midori, Di Minno, Giovanni, d’Oiron, Roseline +4 more·2020·Haematologica
DOI 10.3324/haematol.2019.230771PMC PMC7327664
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Abstract

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors' clinical experience in treating patients with AHA.

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  • Italian, British, and international guidelines on the diagnosis of AHA indicate the need to exclude the presence of LA and investigate an isolated prolonged aPTT that does not correct with a mixing test.

    “Italian, British, and international guidelines on the diagnosis of AHA indicate the need to exclude the presence of LA and investigate an isolated prolonged aPTT that does not correct with a mixing test [101,102,103].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [103]

    The Diagnosis and Mixing tests sections support investigating unexplained, isolated APTT prolongation and considering LA in the differential diagnosis. But the recommendations say LA testing may be performed, not that LA must be absent; they also note that LA can coexist with AHA. A mixing test that does not correct warrants further investigation but cannot itself establish or exclude AHA. (LLM, conf=0.86)

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  • Lupus Anticoagulant Detection under the Magnifying Glass

    Molinari, A. C., Martini, T., Banov, L., Ierardi, A., Leotta, M., Strangio, A., & Santoro, R. C. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206654 · Cited by 9 · see citing works

    “Italian, British, and international guidelines on the diagnosis of AHA indicate the need to exclude the presence of LA and investigate an isolated prolonged aPTT that does not correct with a mixing test [101–103].”
    Background

Authors
Tiede, A., Collins, P., Knoebl, P., Teitel, J., Kessler, C., Shima, M., Di Minno, G., d’Oiron, R., Salaj, P., Jiménez-Yuste, V., Huth-Kühne, A., & Giangrande, P.
Affiliations
  • Medizinische Hochschule Hannover (DE)
  • University Hospital of Wales (GB)
  • St. Michael's Hospital (CA)
  • Georgetown University (US)
  • Nara Medical University (JP)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Institute of Haematology and Blood Transfusion (CZ)
  • University of Oxford (GB)
Corresponding author
Tiede, Andreas
ORCID
Venue
Haematologica
Publisher
Ferrata Storti Foundation (Haematologica)
Published
2020-05-07
Volume
105
Issue
7
Pages
1791-1801
ISSN
  • 0390-6078 (ISSN-L)
  • 1592-8721
DOI
10.3324/haematol.2019.230771
PMC
PMC7327664
OpenAlex
W3021433538
Cited by
401
References
2
Citations by year
2026: 64 · 2025: 62 · 2024: 69 · 2023: 69 · 2022: 74 · 2021: 50 · 2020: 12
FWCI
32.37
Type
journal article
Language
en
Open access
Locations
  • Haematologica (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Novo Nordisk
Topics
  • Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Keywords
acquired hemophilia A, factor VIII inhibitors, neutralizing autoantibodies, activated partial thromboplastin time, bypassing agents, recombinant factor VIIa, activated prothrombin complex concentrate, immunosuppressive therapy, rituximab, cyclophosphamide, corticosteroids, hemorrhage control, prognostic factors, remission
MeSH terms
Rituximab, Animals, Autoantibodies, Blood Coagulation Tests, Factor VIII, Female, Hemophilia A, Hemorrhage, Humans, Male, Swine

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