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3515 Diagnostic and Prognostic Value of Factor VIII Binding Antibodies in Acquired Hemophilia A: Data from the GTH-AH 01/2010 StudyClinically Relevant Abstract

Disorders of Coagulation or Fibrinolysis
Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Andreas Tiede, MD, PhD1, Sonja Werwitzke, MD, PhD1*, Ulrich Geisen, MD, PhD2*, Ulrike Nowak-Göttl, MD, PhD3*, Hermann Eichler, MD, PhD4*, Bernhard Stephan, MD4*, Ute Scholz, MD5*, Holstein Katharina, MD6*, Robert Klamroth7*, Paul Knöbl, MD, PhD8*, Angela Huth-Kühne, MD9* and Barbara Bomke, MD10*

1Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
2Freiburg University Hospital, Freiburg, Germany
3University Medical Center Schleswig-Holstein, Lübeck, Germany
4Saarland University Hospital, Homburg/S., Germany
5Center of Coagulation Disorders, Leipzig, Germany
6Eppendorf University Hospital, Hamburg, Germany
7Vivantes Clinic Friedrichshain, Berlin, Germany
8Medical University Vienna, Vienna, Austria
9Gerinnungsambulanz und Hämophiliezentrum am SRH Kurpfalzkrankenhaus, Heidelberg, Germany
10Heinrich Heine University Medical Center, Düsseldorf, Germany

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.

Disclosures: 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 .

*signifies non-member of ASH