LA detection with new taipan snake venom time and ecarin time reagents insensitive to warfarin, heparin and direct FXa inhibitors.

Introduction Lupus anticoagulant (LA) detection by coagulation assays is compromised by other causes of elevated clotting times. Preponderance of thrombosis in the population warranting LA analysis leads to many requests for testing after initiation of anticoagulation, increasing the likelihood of false positive and negative interpretations in commonly used assays. Taipan snake venom time (TSVT) screening and ecarin time (ET) confirmatory assays are insensitive to vitamin K antagonist and direct factor Xa inhibitors, and all factor deficiencies except prothrombin.

Method TSVT/ET assays were performed on Ceveron s100 (Technoclone). TSVT ratio, ET ratio,% correction, and normalised screen/confirm ratio (NSCR) reference intervals (RI) were derived from 43 normal donors and calculated as±2 standard deviations of the mean. TSVT and ET ratios were derived using RI mean clotting time denominators. TSVT/ET analysis was undertaken on 16 plasmas from non-anticoagulated patients known to have LA, 1 normal and 1 positive control, 10 from warfarinised non-LA patients (INRs 1.90-4.69), 1 warfarinised patient with an LA (INR 4.1), and six non-LA plasmas containing anti Xa DOACs.

Results TSVT ratio, ET ratio,% correction and NSCR RIs all had Gaussian distributions, and upper limits for cut-offs were 1.12/1.09/10.9/1.11 respectively. 14/16 (87.5%) non-anticoagulated LA-positive plasmas had elevated TSVT ratios (range 1.16-1.6) all with confirmed phospholipid dependence via elevated NSCRs (range 1.12-1.53). One of the normal TSVT ratio samples nonetheless returned an elevated NSCR of 1.14, indicating positivity with the integrated interpretive model. Normal control TSVT ratio was 1.06, and positive control TSVT ratio was 1.68 with NSCR of 1.31. All DOAC plasmas had normal TSVT ratios (range 0.90-1.09) and ET ratios (range 0.95-1.06) and no elevated NSCRs. 6/10 of non-LA warfarinised plasmas (INRs 1.90-2.26) had normal TSVT and ET ratios and NSCRs, whilst 4/10 (INRs 3.32-4.69) had elevated TSVT ratios (range 1.25-1.35) but correspondingly elevated ET ratios (range 1.28-1.39), and consequently, no false-positive interpretations as NSCRs were normal. The plasma from a warfarinised patient with an LA returned a TSVT ratio of 1.80 and NSCR of 1.16.

Conclusion Standard LA detection with dilute Russell’s viper venom time and activated partial thromboplastin time is commonly compromised by anticoagulants, and affected by factor deficiencies to which each assay is sensitive. Although charcoal adsorbents can remove direct oral anticoagulants prior to analysis they have their own limitations, whilst TSVT/ET analysis offers a direct route to LA detection in many anticoagulated patients, and is affected by fewer factor deficiencies. TSVT screen has good LA-sensitivity, warranting consideration as first-line assay in appropriately anticoagulated patients before initiating other, less reliable strategies, to reduce anticoagulant interference, and can also be used in non-anticoagulated patients.

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Artikel online veröffentlicht:
26. Februar 2024