Abstract
Background: Acquired hemophilia A (AHA) is a severe bleeding disorder that requires fast and accurate diagnosis as it occurs often unexpectedly in previously healthy men and women of every age. The Nijmegen-modified Bethesda assay (NBA) is the diagnostic gold standard detecting neutralizing anti-FVIII autoantibodies, but is not widely available, not ideal to quantify the complex type 2 inhibitors seen in AHA, and suffers from high inter-laboratory variability.
Objectives: To assess the diagnostic and prognostic value of FVIII binding antibodies as detected by a commercial ELISA (Hyphen Biomed/Coachrom) compared with the NBA.
Methods: Samples and clinical data were available from 102 patients with AHA enrolled in the prospective GTH-AH 01/2010 study. Controls were matched for gender and age. Diagnostic cut-offs were determined by receiver-operator curve (ROC) analysis on training and validation sets, assigned by 1:1 randomization, and by classification and regression tree (CRT) analysis. Prognostic value was assessed by Cox regression analysis of time to partial remission.
Results: Anti-FVIII IgG above the 99th percentile (>15 AU/ml) revealed high sensitivity (1.0, 95% confidence interval [CI] 0.92-1.0) and specificity (1.0, CI 0.92-1.0) to diagnose AHA. The likelihood of achieving remission was strongly related to antibody concentration (anti-FVIII IgG <100 AU/ml: 1.0; 100-<1000 AU/ml: 0.40; ≥1000 AU/ml: 0.21). This association was stronger than that between NBA inhibitor titer and likelihood of remission.
Conclusion: Although the NBA is the gold standard for demonstrating neutralizing antibodies in AHA, the detection of FVIII-binding antibodies by anti-FVIII IgG ELISA is similarly sensitive and specific to diagnose AHA. In addition, anti-FVIII IgG provides important prognostic information.
Tiede:CSL Behring: Consultancy, Honoraria, Research Funding; Baxter: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Investigator, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria; SOBI: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; Biogen Idec: Consultancy, Honoraria; Coachrom: Research Funding; Octapharma: Other: Investigator, Speakers Bureau. Geisen:Roche Diagnostics International AG, Switzerland: Research Funding; Baxalta: Honoraria; Bayer: Research Funding; Novo Nordisk: Consultancy, Honoraria. Nowak-Göttl:Bayer: Consultancy; LFB: Consultancy; Octapharma: Consultancy. Eichler:CSL Behring: Consultancy, Research Funding; Biotest: Consultancy, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Consultancy, Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Klamroth:Bayer, Baxter, CSL Behring, Pfizer, Novo Nordisk, and Octapharma: Honoraria, Research Funding, Speakers Bureau; Biogen and SOBI: Honoraria, Speakers Bureau. Huth-Kühne:Biotest: Consultancy; Baxalta: Consultancy; CSL: Consultancy; Bayer: Consultancy.
Author notes
Asterisk with author names denotes non-ASH members.
![](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/126/23/10.1182_blood.v126.23.3515.3515/3/m_inf01.jpeg?Expires=1722336881&Signature=sQoSDKqzunJv-Oo53CfCoJb8ncmPPk3jWKFtrM6XXQ7ihQK5D7v17hVyRPMfF-sRZdH4-iqz0O5vsRxY2TK2aTMDhbm8426sn4uSfHsqz59RbqTDe5cgFZkYuoecpl9sjH-k38RbN1amoc~hiVtvrK5FKwVHTrG~sNxkjMeNa3W53RCaD-KmIy3hoab77u8vsk6QGv84cFxHpunhShnu5N-7N81jFoS-Tn4ouZq7Sd-js~~E2IB-vn4gE7cIrqM-FpT3-Tx41fsPgfOgZX6u0Jmd1gKL2QVJCIi~n2EiUMdTOBNvYAfY0pPE~HULD6I-Ra3NJdh2iNq5T8RPa6fF4g__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
This icon denotes a clinically relevant abstract
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal