Faculty Collaboration Database

Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening. Am J Hematol 2015 Oct;90(10):871-6

Date

07/07/2015

Pubmed ID

26147783

Pubmed Central ID

PMC4642843

DOI

10.1002/ajh.24104

Scopus ID

2-s2.0-84942196481 (requires institutional sign-in at Scopus site)   10 Citations

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.

Author List

Miller CH, Rice AS, Boylan B, Payne AB, Kelly FM, Escobar MA, Gill J, Leissinger C, Soucie JM, Hemophilia Inhibitor Research Study Investigators

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Autoantibodies
Blood Coagulation Factor Inhibitors
Child
Child, Preschool
Factor VIII
Female
Hemophilia A
Humans
Immunoglobulin G
Infant
Male
Middle Aged
Prospective Studies