Laboratory Diagnosis of Acquired Hemophilia A: Limitations, Consequences, and Challenges
Abstract
Acquired hemophilia A (AHA) should be suspected in patients with a new onset of bleeding and an isolated prolongation of activated partial thromboplastin time. About 10% of patients do not bleed at the time of diagnosis, but are at risk of future bleeding, particularly during interventions or surgery. Diagnosis of AHA is confirmed by demonstrating markedly reduced factor VIII activity (FVIII:C) and neutralizing anti-FVIII antibodies, so-called inhibitors. Several limitations and pitfalls exist with the assays used to diagnose AHA. Interference can result from anticoagulants or lupus anticoagulant. The Bethesda assay used to measure inhibitor potency assumes a log-linear relationship between inhibitor concentration and effect on residual FVIII:C activity to allow exact quantification. However, this relationship is not present for the type 2 inhibitors typically seen in AHA. Therefore, this assay only provides a rough estimate of inhibitor potency. These limitations can explain, in part, why laboratory data, such as inhibitor potency, failed to predict bleeding or response to treatment in AHA. This article reviews the diagnostic approach to AHA, discusses assay-specific limitations and addresses some of the challenges for future research.
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Up to 20% of patients with factor VIII inhibitors can show a positive dRVVT test.
“However, up to 20% of patients with factor VIII inhibitors can show a positive dRVVT test [40].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [40]
LA can cause false positives in Bethesda assays.
“Importantly, LA can cause false positives in Bethesda assays [40].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [40]
dRVVT is very useful for excluding the presence of LA, as this test is less sensitive to factor VIII deficiency; however, up to 20% of patients with factor VIII inhibitors show a positive dRVVT.
“dRVVT is very useful for excluding the presence of LA, as this test is less sensitive to factor VIII deficiency; however, it has been demonstrated that up to 20% of patients with factor VIII inhibitors show a positive dRVVT [40].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [40]
Cites
Update of the guidelines for lupus anticoagulant detection
PENGO, V., TRIPODI, A., REBER, G., RAND, J. H., ORTEL, T. L., GALLI, M., & DE GROOT, P. G. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03555.x · Cited by 1,197 · see citing works
Tripodi, A., Mancuso, M. E., Chantarangkul, V., Clerici, M., Bader, R., Meroni, P. L., Santagostino, E., & Mannucci, P. M. (2005) · Clinical Chemistry · doi:10.1373/clinchem.2005.054312 · Cited by 44 · see citing works
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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
“However, up to 20% of patients with factor VIII inhibitors can show a positive dRVVT test [40]. dRVVT is recommended for its specificity and robustness [9].”
Background
- Authors
- Werwitzke, S., Scharf, R., & Tiede, A.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Tiede, Andreas
- Venue
- Seminars in Thrombosis and Hemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2014-10-09
- Volume
- 40
- Issue
- 07
- Pages
- 803-811
- ISSN
- 0094-6176 (ISSN-L)
- 1098-9064
- OpenAlex
- W2317615448
- Cited by
- 114
- References
- 2
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 17 · 2021: 13 · 2020: 13 · 2019: 7 · 2018: 10 · 2017: 13 · 2016: 7 · 2015: 6 · 2014: 3
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Thrombosis and Hemostasis (publishedVersion)
- PubMed (publishedVersion)
- 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, laboratory diagnosis, factor VIII inhibitors, Bethesda assay, inhibitor potency, anticoagulant interference, lupus anticoagulant, bleeding risk, activated partial thromboplastin time, factor VIII activity
- MeSH terms
- Autoantibodies, Blood Coagulation Tests, Factor VIII, Hemophilia A, Humans, Blood Coagulation Factor Inhibitors, Antibodies, Neutralizing
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