Characterization of the anti‐factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence‐based immunoassay. (11th December 2014)

• Record Type: Journal Article
• Authors: Boylan, B.; Rice, A. S.; Dunn, A. L.; Tarantino, M. D.; Brettler, D. B.; Barrett, J. C.; Miller, C. H.; Abshire, T. C.; Kempton, C. L.; Bockenstedt, P. L.; Di Paola, J. A.; Radhi, M.; Lentz, S. R.; Massey, G.; Neff, A. T.; Shapiro, A. D.; Wicklund, B. M.; Manco‐Johnson, M. J.; Knoll, C.; Escobar, M. A.; Elaine Eyster, M.; Gill, J. C.; Leissinger, C.; Yaish, H.; the Hemophilia Inhibitor Research Study Investigators
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 1(2015:Jan.)
• Page Start: 47
• Page End: 53
• Publication Date: 2014-12-11
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12768
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12768-abs-0001"> <title>Summary</title> <sec id="jth12768-sec-0001" sec-type="section"> <title>Background</title> <p>The development of neutralizing antibodies, referred to as inhibitors, against factor VIII 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.</p> </sec> <sec id="jth12768-sec-0002" sec-type="section"> <title>Objective</title> <p>To assess HA patients' anti‐FVIII antibody profiles as potential predictors of clinical outcomes.</p> </sec> <sec id="jth12768-sec-0003" sec-type="section"> <title>Methods</title> <p>A fluorescence immunoassay (FLI) was used to detect anti‐FVIII antibodies in 491 samples from 371 HA patients.</p> </sec> <sec id="jth12768-sec-0004" sec-type="section"> <title>Results</title> <p>Assessments of antibody profiles showed that the presence of anti‐FVIII IgG<sub>1</sub>, IgG<sub>2</sub> or IgG<sub>4</sub> correlated qualitatively and quantitatively with the presence of an FVIII inhibitor as determined with 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 being NBA‐positive. The FLI detected anti‐FVIII IgG<sub>1</sub> 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 had anti‐FVIII IgG<sub>1</sub> later developed an inhibitor, as compared with two of 33 patients with a negative inhibitor history without anti‐FVIII IgG<sub>1</sub>.</p> </sec> <sec id="jth12768-sec-0005" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>