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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-G�ttl, MD, PhD3*, Hermann Eichler, MD, PhD4*, Bernhard Stephan, MD4*, Ute Scholz, MD5*, Holstein Katharina, MD6*, Robert Klamroth7*, Paul Kn�bl, MD, PhD8*, Angela Huth-K�hne, 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, L�beck, 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 H�mophiliezentrum am SRH Kurpfalzkrankenhaus, Heidelberg, Germany
10Heinrich Heine University Medical Center, D�sseldorf, 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-G�ttl: 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-K�hne: Biotest: Consultancy ; Baxalta: Consultancy ; CSL: Consultancy ; Bayer: Consultancy .

*signifies non-member of ASH