The rapid Bethesda assay is equivalent to the standard Bethesda assay for detection of factor IX inhibitors in patients with severe haemophilia B

Haemophilia. 2020 Jul;26(4):735-740. doi: 10.1111/hae.14028. Epub 2020 May 18.

Abstract

Introduction: The time-dependent nature of factor VIII (FVIII) inhibitors is well described, and the standard FVIII Bethesda assay used to measure inhibitors incorporates a 2-hour incubation. Despite case reports and reviews describing the immediate-acting nature of factor IX (FIX) inhibitors, many coagulation laboratories continue to use a traditional prolonged incubation for FIX Bethesda assays. To our knowledge, a comprehensive evaluation of the FIX Bethesda assay without incubation has not been reported.

Aim: The goal of this study was to evaluate the performance of a rapid FIX Bethesda (ie no incubation) compared with the standard Bethesda assay (2-hour incubation).

Methods: The analysis used a Bethesda assay configured for either immediate testing or a 2-hour incubation. Samples from 14 haemophilia B patients with inhibitors and 9 non-human controls were tested.

Results: The two assays yielded similar performance overall. The average per cent difference in inhibitor titre between the rapid and standard FIX Bethesda assay was -3% (range -15% to +13%; P = .175) for patient samples and -2% (range -17% to +14%; P = .376) for controls.

Conclusion: The rapid Bethesda assay showed good agreement with the standard Bethesda assay for determination of inhibitor levels in patients with severe haemophilia B. The rapid assay allows for faster assessment of inhibitors in patients with severe haemophilia B and has the potential to improve the ability of the coagulation laboratory to perform testing from a logistical viewpoint. Further studies involving larger numbers of patients would be important to confirm our findings.

Keywords: factor IX; haemophilia; inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Coagulation / physiology
  • Blood Coagulation Factor Inhibitors / analysis*
  • Blood Coagulation Tests / standards*
  • Blood Coagulation Tests / statistics & numerical data
  • Blood Coagulation Tests / trends
  • Factor IX / antagonists & inhibitors*
  • Factor IX / immunology
  • Factor IX / metabolism
  • Goats / blood
  • Hemophilia B / blood*
  • Hemophilia B / diagnosis
  • Humans
  • Indicators and Reagents / chemistry
  • Male
  • Mice / blood
  • Models, Animal
  • Reference Standards
  • Severity of Illness Index
  • Sheep / blood

Substances

  • Blood Coagulation Factor Inhibitors
  • Indicators and Reagents
  • Factor IX