Lupus anticoagulant assay cut-offs vary between reagents even when derived from a common set of normal donor plasmas

Background Multicenter studies reveal that diagnostic efficacy of lupus anticoagulant (LA) assays is enhanced if cut-offs are locally generated. However, a potential confounder is the inevitable use of separate normal donor populations. Objectives Generate cut-offs for multiple LA reagents with the same analyzer and normal donor plasmas. Methods Cut-offs for screen ratio, confirm ratio, percent correction of screen ratio by confirm ratio, and normalized screen/confirm ratio (NSCR) were derived from the same 50 normal donor plasmas for screen and confirm pairs for two dilute Russell's viper venom time reagents, LA1/LA2 and HEMOCLOT (TM) LA-S/LA-C, and two APTTs, Actin FSL/FS and Cephen LS/Cephen. The cut-offs were challenged with plasmas from 20 triple-positive APS patients and 25 plasmas from LA-negative, thrombotic patients. Results Cut-offs for screen ratio, confirm ratio, percent correction, and NSCR, respectively, were 1.12/1.08/8.3/1.09 for LA1/LA2; 1.17/1.10/13.6/1.13 for HEMOCLOT (TM) LA-S/LA-C; 1.12/1.13/9.7/1.10 for Actin FSL/FS; 1.09/1.13/11.0/1.11 for Cephen LS/Cephen. LA1 and LA-S screens were elevated in 19/20 and 16/20 triple-positive plasmas, respectively, while 20/20 were detected with both via integrated interpretation ie, percent correction or NSCR irrespective of screen elevation. Actin FSL and Cephen LS screens were elevated in 17/20 and 19/20 triple-positive plasmas, respectively, while one more LA was detected with Actin FSL via integrated interpretation, but not for Cephen LS. Integrated interpretation suggested 5/25 LA-negative plasmas contained weak LA (two with Actin FSL/FS, two with LA1/LA2, one with LA-S/LA-R). Conclusions Employing the same normal donor plasmas and analytical platform does not compensate for between-reagent differences when generating LA assay cut-offs.