Laboratory diagnostic outcome applying detection criteria recommended by the Scientific and Standardization Committee of the ISTH on Lupus Anticoagulant

Summary

This study shows the diagnostic outcome of an APTT-based and two dRVVT-based commercial confirmatory integrated tests with the application of the recommendations by the Scientific and Standardization Committee (SSC) on Lupus anticoagulant (LA)/antiphospholipid syndrome (APS) of the International Society on Thrombosis and Haemostasis (ISTH) issued in 2009 concerning the cut-off values for the screening, mixing and confirmatory tests for the detection of LA and the mandatory need to perform mixing tests of patient plasma with pooled normal plasma. The study population included 565 patients collected from a large central coagulation laboratory, for which the attending physicians requested LA detection. One-hundred-six healthy subjects (HS) and 131 selected patients on oral anticoagulant therapy (OAT) were included as negative controls. The results suggest that the performance of mixing tests is indicated for those methods with relatively poor specificity, but is less needed for those methods with high specificity. Furthermore, the SSC recommendation to use normal mid-value (i.e. the 50th percentile of distribution of results from healthy subjects) as the cut-off to interpret results of confirmatory tests, showed a modest increase in LA detection rate (sensitivity) but at the expense of specificity, particularly in methods with low specificity.

Keywords

Lupus anticoagulant - laboratory diagnosis criteria - cut-off values - mixing test

• References

• 1 Pengo V, Tripodi A, Reber G. et al. Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2009; 07: 1737-1740.
• 2 Brandt JT, Triplett DA, Alving B. et al. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 1995; 74: 1185-90.
• 3 Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun 2000; 15: 145-151.
• 4 Pengo V, Biasiolo A, Gresele P. et al. Survey on lupus anticoagulant diagnosisby central evaluation of positive plasma samples. J Thromb Haemost 2007; 05: 925-930.
• 5 Rosner E, Pauzner R, Lusky A. et al. Detection and quantitative evaluation of lupus circulating anticoagulant activity. Thromb Haemost 1987; 57: 144-147.
• 6 Devreese KMJ. No more mixing tests required for integrated assay systems in the laboratory diagnosis of lupus anticoagulants?. J Thromb Haemost 2010; 08: 1120-1122.
• 7 Chantarangkul V, Tripodi A, Arbini A. et al. Silica clotting time (SCT) as a screening and confirmatory test for detection of the lupus anticoagulants. Thromb Res 1992; 67: 355.
• 8 Tripodi A, Chantarangkul V, Clerici M. et al. Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA. Thromb Haemost 2002; 88: 583-586.
• 9 Thom J, Ivey L, Eikelboom J. Normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulant. J Thromb Haemost 2003; 01: 2689-2691.
• 10 Devreese KM. Interpretation of normal plasma mixing studies in the laboratory diagnosis of lupus anticoagulants. Thromb Res 2007; 119: 369-376.
• 11 Aboud M, Roddie C, Ward C. et al. To Mix with Pooled Normal Plasma or Not to Mix: A Comparative Study of 2 Approaches for Assessing Lupus Anticoagulant Inhibitory Activity in the Dilute Russell Viper Venom Method. Clin Chem 2007; 53: 143-145.
• 12 Ledford-Kraemer MR. Laboratory Testing for Lupus Anticoagulants: Preexam-ination Variables, Mixing Studies, and Diagnostic Criteria. Semin Thromb Hemost 2008; 34: 380-388.
• 13 Moore GW, Savidge GF. The dilution effect of equal volume mixing studies compromises confirmation of inhibition by lupus anticoagulants even when mixture specific reference ranges are applied. Thromb Res 2006; 118: 523-528.
• 14 Favaloro EJ, Bonar R, Zebeljan D. et al. Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 2010; 08: 2828-2831.
• 15 Tripodi A, Pengo V. More on: laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 2011; 09: 2126-2127.
• 16 Tripodi A. Laboratory testing for lupus anticoagulants: diagnostic criteria and use of screening, mixing, and confirmatory studies. Semin Thromb Hemost 2008; 34: 373-379.
• 17 Moore GW, Henley A, Greenwood CK. et al. Further evidence of false negative screening for lupus anticoagulants. Thromb Res 2008; 121: 477-484.
• 18 Reber G, Meijer P. In ECAT veritas?. Lupus 2012; 21: 722-724.
• 19 Tripodi A. To mix or not to mix in lupus anticoagulant testing?. That is the question. Semin Thromb Hemost 2012; 38: 385-389.
• 20 Pengo V, Biasiolo A, Gresele P. et al. A comparison of lupus anticoagulant-positive patients with clinical picture of antiphospholipid syndrome and those without. Arterioscler Thromb Vasc Biol 2007; 27: e309-310.