title: Investigations from external quality assurance programs reveal a high degree of variation in the laboratory identification of coagulation factor inhibitors.
abstract: The laboratory has a key role in the initial detection of factor inhibitors and an ongoing role in the measurement of inhibitor titers during the course of inhibitor eradication therapy. The most commonly seen factor inhibitors are those directed against factor VIII (FVIII), usually detected either with the original or the Nijmegen-modified Bethesda assay. In addition, several circumstances can arise in which the laboratory may test samples that potentially reflect false identification of factor inhibitors. These include lupus anticoagulants and other events generally related to preanalytical variables, including incorrect sample presentations. This article reviews each of these elements, largely from the perspective of cross-laboratory studies undertaken within the framework of external quality assurance (EQA), a peer-laboratory process that aims to assess the ongoing performance of groups of similar laboratories. This review details the experience of the Royal College of Pathologists of Australasia Haematology Quality Assurance Program, and it also reflects on the experience of other EQA organizations. Our analysis reveals a wide variety of test practice among inhibitor testing laboratories, a wide variation in detected inhibitor levels in cross-tested samples, and substantial evidence of false-positive and false-negative detection of factor inhibitors. These findings hold some significance for the clinical management of patients affected by these inhibitors. There is still much need for standardization and improvement in factor inhibitor detection, and we hope that this report provides a basis for future improvements in this area.
authors.affiliation: Department of Haematology, NSW, Australia.
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Favaloro
authors.forename: Roslyn
authors.initials: R
authors.lastname: Bonar
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kershaw
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Duncan
authors.forename: John
authors.initials: J
authors.lastname: Sioufi
authors.forename: Katherine
authors.initials: K
authors.lastname: Marsden
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis*; D001779:Blood Coagulation Factors; D001780:Blood Coagulation Tests / Q000592:standards*; D001800:Blood Specimen Collection / Q000379:methods; D005169:Factor VIII / Q000037:antagonists & inhibitors; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000032:analysis; D015588:Observer Variation; D011785:Quality Assurance, Health Care; D012680:Sensitivity and Specificity; D013048:Specimen Handling
chemical_list: D001323:Autoantibodies; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D016682:Lupus Coagulation Inhibitor; D005169:Factor VIII