title: Measurement of von Willebrand factor-cleaving protease (ADAMTS-13) activity in plasma: a multicenter comparison of different assay methods.
abstract: A severely deficient ADAMTS-13 activity (<5%) is a key laboratory finding confirming the diagnosis of thrombotic thrombocytopenic purpura (TTP), whereas a mildly or moderately decreased activity is found in various other conditions. Laboratory tests for ADAMTS-13 activity must reliably identify a severe deficiency and detect inhibitory antibodies against ADAMTS-13. We carried out a multicenter comparison of different assays for ADAMTS-13 activity in plasma, including the quantitative immunoblotting of degraded von Willebrand factor (VWF) substrate, the residual collagen binding activity and ristocetin cofactor activity of degraded VWF, and an immunoradiometric assay. The main goal was to investigate whether all assays concordantly identified severe ADAMTS-13 deficiency and detected inhibitory antibodies. ADAMTS-13 activity was determined by five laboratories in 30 plasma samples of patients with hereditary and acquired TTP and other conditions. ADAMTS-13 activity values of the samples ranged from <3% to > 100%. Concerning the identification of a severe ADAMTS-13 deficiency, good interassay and interlaboratory agreement was observed with only one false-negative and two false-positive results by two laboratories using a collagen binding assay. For samples with normal or mildly to moderately reduced ADAMTS-13 activity, results were less concordant. There was good agreement for the detection of strong inhibitors. We conclude that all assays investigated are useful as a screening test in suspected TTP. Further assay improvement is needed, however.
authors.affiliation: Central Hematology Laboratory, Inselspital, University Hospital, Bern, Switzerland.
authors.forename: J-D
authors.initials: JD
authors.lastname: Studt
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: J-P
authors.initials: JP
authors.lastname: Girma
authors.forename: K
authors.initials: K
authors.lastname: Varadi
authors.forename: B
authors.initials: B
authors.lastname: Lämmle
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D001323:Autoantibodies / Q000097:blood; D004796:Clinical Enzyme Tests / Q000379:methods* / Q000592:standards; D003951:Diagnostic Errors; D006801:Humans; D008666:Metalloendopeptidases / Q000097:blood* / Q000172:deficiency / Q000276:immunology; D015588:Observer Variation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human