title: Interlaboratory variation in factor VIII:C inhibitor assay results is sufficient to influence patient management: data from the UK national quality external assessment scheme for blood coagulation.
abstract: We report the results of external quality assessment exercises in which 60 to 120 centers performed factor VIII (FVIII) inhibitor testing on a series of samples over a 13-year period. Samples from seven different subjects were distributed for analysis comprising the following: four different subjects with severe hemophilia A with antibodies following replacement therapy, one subject with acquired hemophilia A and antibodies to FVIII, one subject with normal FVIII and an easily detected lupus anticoagulant, and one subject with mild hemophilia A and a difficult-to-detect lupus anticoagulant but without antibodies to FVIII. In all of the surveys the results obtained in different centers analyzing the same sample varied to an extent that would influence patient management decisions. In the UK National External Quality Assessment Scheme surveys reported here, there was considerable interlaboratory variation in the results of FVIII inhibitor testing that did not improve over the survey period. The coefficient of variation of results in different centers was between 33% and 106% in samples from patients with severe congenital hemophilia A. In some cases, results were affected by assay components. For one plasma, the mean FVIII inhibitor results in centers using one source of normal plasma was 3.9 Bethesda unit (BU)/mL compared with a mean of 5.7 BU/mL in centers using a different normal plasma source ( P = 0.04). Our data indicate that the detection of FVIII inhibitors is not the same in different centers, and the degree of variability noted makes it likely that assay variability has contributed to the lack of international consensus in relation to the real incidence of FVIII inhibitors in different clinical settings. Improvements in assay standardization are urgently needed.
authors.affiliation: United Kingdom National External Quality Assessment Scheme (Blood Coagulation), Sheffield, United Kingdom. steve.kitchen@sth.nhs.uk
authors.forename: Steve
authors.initials: S
authors.lastname: Kitchen
authors.forename: Ian
authors.initials: I
authors.lastname: Jennings
authors.forename: F Eric
authors.initials: FE
authors.lastname: Preston
authors.forename: Dianne P
authors.initials: DP
authors.lastname: Kitchen
authors.forename: Tim A L
authors.initials: TA
authors.lastname: Woods
authors.forename: Isobel D
authors.initials: ID
authors.lastname: Walker
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D001780:Blood Coagulation Tests / Q000592:standards*; D005169:Factor VIII / Q000276:immunology; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D011785:Quality Assurance, Health Care; D012680:Sensitivity and Specificity; D006113:United Kingdom
chemical_list: D001323:Autoantibodies; D001779:Blood Coagulation Factors; D005169:Factor VIII; C065655:anti-inhibitor coagulant complex