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Semin Thromb Hemost 2009; 35(8): 752-759
DOI: 10.1055/s-0029-1245107
© Thieme Medical Publishers

Improvements in Factor VIII Inhibitor Detection: From Bethesda to Nijmegen

Bert Verbruggen1 , Waander L. van Heerde1 , Britta A.P Laros-van Gorkom2
  • 1Department of Laboratory Medicine, Laboratory of Hematology, Nijmegen, The Netherlands
  • 2Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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Publication History

Publication Date:
18 February 2010 (online)

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ABSTRACT

All methods for the detection of factor VIII (FVIII) inhibitors are based on the measurement of inactivation of FVIII in a mixture of the test plasma containing the putative inhibitor and an exogenous source of FVIII. Various types of assays have been developed since the first inhibitor was described in 1941. Nowadays, two methods are preferably used, the Bethesda assay and the Nijmegen assay. Although the Nijmegen assay shows a better specificity and intra- and interlaboratory variation, it is still hampered by several limitations related to assay characteristics (pH, temperature, and time of incubation), type of control sample, and the von Willebrand factor content of the assay mixture. Epitope specificity plays an important role in the reliability of functional assays because inhibitors against the C2 domain are more difficult to quantify compared with inhibitors against the A2 domain. Finally, lupus anticoagulants can interfere with inhibitor assays, resulting in aberrant results. This report describes in detail the various problems encountered with the assays used in the quantification of functional FVIII inhibitors.

KEYWORDS

Factor VIII - inhibitors - hemophilia - Bethesda assay - Nijmegen assay

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H. VerbruggenM.D. 

468 Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre

Geert Grooteplein 8, 6525 GA Nijmegen, The Netherlands

Email: h.verbruggen@chl.umcn.nl

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