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DOI: 10.1055/s-0037-1616765
The Type of Factor VIII Deficient Plasma Used Influences the Performance of the Nijmegen Modification of the Bethesda Assay for Factor VIII Inhibitors
Publication History
Received
30 November 2000
Accepted after revision
10 September 2001
Publication Date:
12 December 2017 (online)
Summary
We have investigated the influence of the type of factor VIII deficient plasma used on the assay results of the Nijmegen modification of the Bethesda method for factor VIII inhibitors. Immuno depleted factor VIII deficient plasmas, lacking besides factor VIII also von Willebrand factor, gave decreased inhibitor titres compared to assay results with factor VIII deficient plasmas containing von Willebrand factor suggesting the need of the latter in the test system for the stability of factor VIII:C. Moreover the performance of the assay with immuno depleted plasma was contaminated in a certain type of this plasma by the presence of a factor VIII:C inhibitor. Chemically depleted factor VIII deficient plasma appeared to give falsely elevated titres when used in combination with other types of deficient plasmas as substrate plasma in the factor VIII:C assay due to the presence of activated factor Va in the preparation. Suggestions are described with respect to the observed limitations in order to obtain reliable results.
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References
- 1 Rasi V, Ikkala E. Haemophiliacs with factor VIII inhibitors in Finland: prevalence, incidence and outcome. Brit J Haemat 1990; 76 (Suppl. 03) 369-71.
- 2 Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Gungor T, Krachhardt B, Kornhuber B. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. The Lancet 1992; 339: 594-8.
- 3 Addiego J, Kasper C, Abildgaard C, Hilgartner M, Lusher J, Glader B, Aledort L. Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII. The Lancet 1993; 342: 462-4.
- 4 Lusher JM, Arkin S, Abildgaard CF, Schwarz RS. Recombinant factor VIII for the treatment of previously untreated patients with haemophilia A. N Engl J Med 1993; 328: 453-9.
- 5 Vermylen J. How do some haemophiliacs develop inhibitors?. Haemophilia 1998; 4: 538-42.
- 6 Bert Verbruggen, Irena Novákovà, Hans Wessels, Jan Boezeman, Marijke van den Berg, Eveline Mauser-Bunschoten. The Nijmegen Modification of the Bethesda Assay for Factor VIII:C Inhibitors: Improved Specificity and Reliability. Thromb Haemost 1995; 73 (Suppl. 02) 247-51.
- 7 Kasper C, Aledort L, Counts R, Edson J, Fratantone J, Green D, Hempton J, Hilgartner M, Lazarson J, Levin P, Macmillan C, Pool J, Shapiro S, Schulman N, Eyes J. A more uniform measurement of factor VIII-inhibitors. Thromb Diath Haemorrh 1975; 34: 869-72.
- 8 Alan R, Giles AR, Bert Verbruggen, Georges E, Rivard Jerome Teitel, Irwin Walker. and the Association of Hemophilia Centre Directors of Canada A Detailed Comparison of the Performance of the Standard versus The Nijmegen Modification of the Bethesda Assay in Detecting Factor VIII:C Inhibitors in the Haemophilia A Population of Canada. Thromb Haemost 1998; 79: 872-5.
- 9 Van den Brink EN, Turenhout EAM, Davies J, Bovenschen N, Fijnvandraat K, Ouwehand WH, Peters M, Voorberg J. Human Antibodies with Specificity for the C2 domain of factor VIII are derived from germline genes. Blood 2000; 95: 558-63.
- 10 Nesheim ME, Katzmann JA, Tracy PB, Mann KG. “Factor V” in. Methods in Enzymology 1981; 80: 249-74.
- 11 Macfarlane DE, Stibbe J, Zucker MB, Grant RA, McPherson J. A Method for Assaying von Willebrand Factor (Ristocetin Cofactor). Thromb Haemost 1975; 34: 306-8.
- 12 Chantarangkul V, Ingram GIC, Thorn MB, Darby SC. An Artificial ‘Haemophilic’ Plasma for One-Stage Factor-VIII Assay. British Journal of Haematology 1978; 40: 471-88.