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

Details

• Alternative Title:
  Am J Hematol
• Personal Author:
  Miller, Connie H. ; Rice, Anne S. ; Boylan, Brian ; Payne, Amanda B. ; Kelly, Fiona M. ; Escobar, Miguel A. ; Gill, Joan ; Leissinger, Cindy ; Soucie, J. Michael
• Corporate Authors:
  Hemophilia Inhibitor Research Study Investigators
• Description:
  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.
• Subjects:
  Adolescent Adult Autoantibodies Blood Coagulation Factor Inhibitors Child Child, Preschool Factor VIII Female Hemophilia A Humans Immunoglobulin G Infant Male Middle Aged Prospective Studies

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• Source:
  Am J Hematol. 90(10):871-876
• Pubmed ID:
  26147783
• Pubmed Central ID:
  PMC4642843
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHSUnited States/
• Volume:
  90
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:45edc3ab17f9a5c7e3b101b4ad66c354845ee9f2b4ee5edd60f9cb6c4af45089
• Download URL:
  https://stacks.cdc.gov/view/cdc/36468/cdc_36468_DS1.pdf
• File Type:
  [PDF - 391.88 KB ]