Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2015 Oct;90(10):871-6.
doi: 10.1002/ajh.24104. Epub 2015 Sep 10.

Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening

Connie H Miller  1 , Anne S Rice  1 , Brian Boylan  1 , Amanda B Payne  1 , Fiona M Kelly  1 , Miguel A Escobar  2 , Joan Gill  3 , Cindy Leissinger  4 , J Michael Soucie  1 ; Hemophilia Inhibitor Research Study Investigators
Affiliations
Comparative Study

Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening

Connie H Miller et al. Am J Hematol. 2015 Oct.

Abstract

Characteristics of inhibitors identified by prospective screening may differ from those detected clinically. In a prospective study at 17 hemophilia centers with central inhibitor measurement by Nijmegen-Bethesda assay, 23 (2.8%) of 824 hemophilia A patients had new inhibitors detected: nine high-titer inhibitors (HTI: 7 ≥ 5.0 NBU plus 2 of 2.6 and 3.4 NBU at immune tolerance induction initiation) and 14 low-titer inhibitors (LTI: 0.5-1.9 NBU). HTI occurred at an earlier age (median 2 years, range 1-18, vs. median 11 years, range 2-61, P = 0.016). Both HTI (22%) and LTI (43%) occurred in non-severe patients. All HTI, but only 64% of LTI, were found to be FVIII-specific by chromogenic Bethesda assay or fluorescence immunoassay (FLI), indicating a high rate of false-positive LTI. Repeat specimens confirmed all HTI, 7/9 LTI, and 7/7 FVIII-specific LTI. FLI results were similar between HTI and FVIII-specific LTI; all included IgG1 and IgG4 subclasses. A comparable prospective study conducted from 1975 to 1979 at 13 U.S. centers found 31 (2.4%) new inhibitors among 1,306 patients. In both studies, one-third of inhibitors occurred in non-severe patients and one-quarter after 150 exposure days (ED). Significant differences were seen in the age at which inhibitors occurred (median 16 years in the older study vs. 5 years currently, P = 0.024) and in ED before inhibitor development, 10% in the older study and 43% currently study occurring within 20 ED, suggesting a temporal change in inhibitor development. Prospective screening detects inhibitors in patients of all severities, ages, and ED. Some LTI, however, are false positives.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: Nothing to report.

Figures

Figure 1
Figure 1
Comparison of high titer and low titer inhibitors for age at inhibitor detection (A) and exposure days before inhibitor detection (B). Bar represents the median.
Figure 2
Figure 2
Comparison of 1975–1979 study [2] and current study for age at inhibitor detection (A) and exposure days before inhibitor detection (B). Bar represents the median.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Soucie JM, Miller CH, Kelly FM, Aschman D, DiMichele D, Konkle BA, Kulkarni R Monahan PE the CDC. Inhibitor Surveillance Working Group. National surveillance for hemophilia inhibitors in the United States: summary report of an expert meeting. Am J Hematol. 2014;89:621–625. - PMC - PubMed
    1. McMillan CW, Shapiro SS, Whitehurst D, Hoyer LW, Rao AV, Lazerson J. The natural history of factor VIII:C inhibitors in patients with hemophilia A: A national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors. Blood. 1988;71:344–348. - PubMed
    1. Soucie JM, Miller CH, Kelly FM, Payne AB, Creary M, Bockenstedt PL, Kempton CL, Manco-Johnson MJ, Neff AT the Haemophilia Inhibitor Research Study Investigators. A study of prospective surveillance for inhibitors among persons with haemophilia in the United States. Haemophilia. 2014;20:230–237. - PMC - PubMed
    1. Miller CH, Platt SJ, Rice AS, Kelly F, Soucie JM the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen–Bethesda assay modifications to allow inhibitor measurement during replacement therapy and facilitate inhibitor surveillance. J Thromb Haemost. 2012;10:1055–1061. - PMC - PubMed
    1. Miller CH, Rice AS, Boylan B, Shapiro AD, Lentz SR, Wicklund BM, Kelly FM, Soucie JM the Hemophilia Inhibitor Research Study Investigators. Comparison of clot-based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the U.S. Hemophilia Inhibitor Research Study. J Thromb Haemost. 2013;11:1300–1309. - PMC - PubMed

Publication types