Assay discrepancy in mild haemophilia A: entire population study in a National Haemophilia Centre

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 15; no. 1; pp. 285 - 289
• Main Authors: POULSEN, A. L., PEDERSEN, L. H., HVAS, A.-M., POULSEN, L. H., THYKJÆR, H., INGERSLEV, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2009
• Subjects: assay discrepancy; Blood Coagulation Tests - methods; Chromogenic Compounds; Factor VIII - analysis; haemophilia; Hemophilia A - blood; Hemophilia A - genetics; Humans; Male; mild haemophilia; Patient Selection; Reproducibility of Results
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/j.1365-2516.2008.01899.x

Assay discrepancy in mild haemophilia, here defined by a significantly higher factor VIII (FVIII):C response by the one‐stage procoagulant assay as compared with a two‐stage enzymatic method, has repeatedly been reported in literature. The purpose of this study was to determine the overall prevalence of this phenomenon amongst mild haemophilia families from a population of 2.95 million inhabitants in the Western Danish region. Information was collected retrospectively through a thorough search of archives of the National Haemophilia Centre in Aarhus. We identified 109 patients with mild haemophilia A amongst whom 92 were eligible to enter the study. These represent a total of 53 unrelated families. Our data illustrate that this assay discrepancy pattern is found quite frequently amongst our mild haemophilia A families. While the ratio of FVIII:C chromogenic/FVIII:C clot values was quite consistent amongst patients belonging to same family pattern, ratios in the entire cohort of families ranged from 0.18 to 1.00. Selecting a cut‐off level for the FVIII:C chromogenic/FVIII:C clot ratios at 0.7, 0.6 and 0.5, respectively, we found that 38 (72%), 27 (51%) and 19 (36%) of families, respectively, displayed this assay discrepancy. In 10 patients, the FVIII:C chromogenic level was inside the category of moderate haemophilia at >0.01–<0.05 IU mL−1, pointing to a class‐shift in the biochemical phenotype. In conclusion, our data illustrate a substantial prevalence of the assay discrepancy phenomenon amongst mild haemophilia A patients in our geographical area.