Details:

Alternative Title:
J Thromb Haemost
Publisher's site:
http://dx.doi.org/10.1111/jth.12768
Personal Author:
Boylan, Brian ; Rice, Anne S. ; Dunn, Amy L. ; Tarantino, Michael D. ; Brettler, Doreen B. ; ... More +
Boylan, Brian ; Rice, Anne S. ; Dunn, Amy L. ; Tarantino, Michael D. ; Brettler, Doreen B. ; Barrett, John C. ; Miller, Connie H. ; Less -
Corporate Authors:
Hemophilia Inhibitor Research Study Investigators ;
Description:
Background The development of neutralizing antibodies, referred to as inhibitors, against factor VIII (FVIII) is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective Assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2, or IgG4 correlated qualitatively and quantitatively with the presence of a FVIII inhibitor as reported by the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and a positive anti-FVIII IgG1 later developed an inhibitor, compared to 2 of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.
Subject:
[+]
Adolescent
Article
Autoantibodies
Biomarkers
Factor VIII
Factor VIII Deficiency
Fluorescence Polarization Immunoassay
Hemophilia A
Humans
Immunoassay
Immunoglobulin G
Inherited Blood Coagulation Disorders
Male
Predictive Value Of Tests
Prognosis
Spectrometry, Fluorescence
Time Factors
Young Adult

Source:
J Thromb Haemost. 13(1):47-53. ;
Pubmed ID:
25354263
Pubmed Central ID:
PMC4383171
Document Type:
Journal Article ;
Funding:
CC999999/Intramural CDC HHS/United States ;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:9d3479c397e2ab72f2ab0113b65ec9e4fdbaccca22049db957b8d2dafcbceeaa
File Type:

Supporting Files

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