Journal article
Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening
American journal of hematology, Vol.90(10), pp.871-876
10/2015
DOI: 10.1002/ajh.24104
PMCID: PMC4642843
PMID: 26147783
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.
Details
- Title: Subtitle
- Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening
- Creators
- Connie H Miller - National Center on Birth Defects and Developmental DisabilitiesAnne S Rice - National Center on Birth Defects and Developmental DisabilitiesBrian Boylan - National Center on Birth Defects and Developmental DisabilitiesAmanda B Payne - National Center on Birth Defects and Developmental DisabilitiesFiona M Kelly - National Center on Birth Defects and Developmental DisabilitiesMiguel A Escobar - Gulf States Hemophilia and Thrombophilia Center, Houston, TexasJoan Gill - Medical College of WisconsinCindy Leissinger - Louisiana Center for Bleeding and Clotting Disorders, New Orleans, LouisianaJ Michael Soucie - National Center on Birth Defects and Developmental DisabilitiesHemophilia Inhibitor Research Study Investigators
- Contributors
- Steven R Lentz (Contributor) - University of Iowa, Hematology, Oncology, and Blood & Marrow Transplantation
- Resource Type
- Journal article
- Publication Details
- American journal of hematology, Vol.90(10), pp.871-876
- DOI
- 10.1002/ajh.24104
- PMID
- 26147783
- PMCID
- PMC4642843
- NLM abbreviation
- Am J Hematol
- ISSN
- 0361-8609
- eISSN
- 1096-8652
- Grant note
- CC999999 / Intramural CDC HHS
- Language
- English
- Date published
- 10/2015
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359765602771
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