title: Mixing test specific cut-off is more sensitive at detecting lupus anticoagulants than index of circulating anticoagulant.
abstract: BACKGROUND
  Recent guidelines for lupus anticoagulant (LA) detection recommend mixing test interpretation with either a mixing test-specific cut-off (MTC) or index of circulating anticoagulant (ICA). Few studies directly compare efficacy of these approaches. We retrospectively applied MTC and ICA assessment to raw data of 350 LA-positive plasmas from non-anticoagulated patients to compare detection rates of inhibition.
  
  
  METHODS
  Screen and confirm dRVVT and dilute APTT assays were performed on undiluted plasma and 1:1 mixtures with normal pooled plasma. Samples were considered LA-positive if one or both screening test ratios were elevated and corrected by ≥10% with the confirmatory test. Mixing tests were assessed against locally derived cut-offs for MTC (dRVVT >1.13, dAPTT >1.15) and ICA (dRVVT >11.9%, dAPTT >13.2%).
  
  
  RESULTS
  105 of 350 (30%) were positive in dRVVT and dAPTT, 109/350 (31.1%) were dRVVT positive only and 136/350 were dAPTT positive only (38.9%), from undiluted plasma results. Of the 214 dRVVT positive plasmas, 53 (24.8%) were negative for inhibition by MTC and 65 (30.4%) negative by ICA. Of the 241 dAPTT positive plasmas, 48 (19.2%) were negative by MTC and 97 (40.2%) negative by ICA.
  
  
  CONCLUSIONS
  Whilst integrated testing often detects LA without mixing tests they are diagnostically useful in certain circumstances. Thus, it is valuable to maximise mixing test interpretation as the dilution can lead to false-negative results. These data on a large cohort of LA-positive plasmas reveal that, with the reagents and equipment employed, MTC is superior to ICA in detecting the in vitro inhibition of LA.
authors.affiliation: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK. Electronic address: gary.moore@viapath.co.uk.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Moore
authors.affiliation: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Culhane
authors.affiliation: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Daw
authors.affiliation: Department of Haemostasis and Thrombosis, Viapath Analytics, Guy's & St. Thomas' Hospitals, London, UK.
authors.forename: Charlotte P
authors.initials: CP
authors.lastname: Noronha
authors.affiliation: Haemostasis Product Engineering, Sysmex Corporation, Kobe, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kumano
mesh_terms: D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000175:diagnosis; D001780:Blood Coagulation Tests / Q000379:methods*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis*; D016682:Lupus Coagulation Inhibitor / Q000032:analysis*; D010314:Partial Thromboplastin Time
chemical_list: D007136:Immunoglobulins; D016682:Lupus Coagulation Inhibitor; C019158:circulating anticoagulants
keywords: APTT; Antiphospholipid antibodies; Index of circulating anticoagulant; Mixing tests; dRVVT