Comparison of Clot-based, Chromogenic, and Fluorescence Assays for Measurement of Factor VIII Inhibitors in the U.S. Hemophilia Inhibitor Research Study

Details

• Alternative Title:
  J Thromb Haemost
• Personal Author:
  Miller, Connie H. ; Rice, Anne S. ; Boylan, Brian ; Shapiro, Amy D. ; Lentz, Steven R. ; Wicklund, Brian M. ; Kelly, Fiona M. ; Soucie, J. Michael
• Corporate Authors:
  Hemophilia Inhibitor Research Study Investigators
• Description:
  Background ; Detection and validation of inhibitors (antibodies) to hemophilia treatment products are important for clinical care, evaluation of product safety, and assessment of population trends. ; Methods ; Centralized monitoring for factor VIII (FVIII) inhibitors was conducted for patients in the Hemophilia Inhibitor Research Study using a previously reported modified Nijmegen-Bethesda clotting assay (NBA), a chromogenic Bethesda assay (CBA), and a novel fluorescence immunoassay (FLI). ; Results ; NBA and CBA were performed on 1005 specimens and FLI on 272 specimens. CBA was negative on 880/883 specimens (99.7%) with Nijmegen-Bethesda units (NBU)<0.5 and positive on 42/42 specimens (100%) with NBU≥2.0 and 43/80 specimens (53.8%) with NBU 0.5–1.9. Among specimens with positive NBA and negative CBA, 58.1% were FLI-negative, 12.9% had evidence of lupus anticoagulant, and 35.5% had non-time-dependent inhibition. CBA and FLI were positive on 72.4% and 100% of 1.0–1.9 NBU specimens and 43.1% and 50.0% of 0.5–0.9 NBU specimens. FLI detected antibodies in 98.0% of CBA-positive and 81.6% of NBA-positive specimens (P=0.004). Among 21 new inhibitors detected by NBA, 5 (23.8%) with 0.7–1.3 NBU did not react in CBA or FLI. Among previously positive patients with 0.5–1.9 NBU, 7/25 (28%) were not CBA or FLI positive. FLI was positive on 36/169 NBU-negative specimens (21.3%). ; Conclusions ; FVIII specificity could not be demonstrated by CBA or FLI for 26% of inhibitors of 0.5–1.9 NBU; such results must be interpreted with caution. Low titer inhibitors detected in clot-based assays should always be repeated, with consideration given to evaluating their reactivity with FVIII using more specific assays.
• Subjects:
  • Adolescent
  • Adult
  • Autoantibodies
  • Biomarkers
  • Blood Coagulation
  • Blood Coagulation Tests
  • Child
  • Child, Preschool
  • Chromogenic Compounds
  • Factor VIII
  More +
• Keywords:
  • factor VIII inhibitor
  • Nijmegen-Bethesda assay
  • chromogenic factor VIII assay
  • fluorescence immunoassay
• Source:
  J Thromb Haemost. 11(7):1300-1309
• Pubmed ID:
  23601690
• Pubmed Central ID:
  PMC4477744
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHSUnited States/
• Volume:
  11
• Issue:
  7
• Download URL:
  https://stacks.cdc.gov/view/cdc/31742/cdc_31742_DS1.pdf
• File Type:
  [PDF - 849.05 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5e149ffc937bc976965f534081301015d47f3f1fa3caa682d7c8274d2972e734