The Activated Seven Lupus Anticoagulant Assay Detects Clinically Significant Antibodies

Abstract

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay.

Keywords

activated seven lupus anticoagulant assay antiphospholipid syndrome lupus anticoagulants

References

Arnout J. Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. Thromb Haemost. 2001; 86:83-91.

Bick RL The antiphospholipid thrombosis syndromes: a common multidisciplinary medical problem. Clin Appl Thromb Haemost. 1997;3:270-283.

Öztürk MA , Haznedaroğlu IC , Turgut M. , et al. Current debates in antiphospholipid syndrome: the acquired antibody-mediated thrombophilia. Clin Appl Thromb Haemost. 2004 ;10:89-126.

Lawrie AS , Mackie IJ , Purdy G. , et al. The sensitivity and specificity of commercial reagents for the detection of lupus anticoagulant show marked differences in performance between photo-optical and mechanical coagulometers. Thromb Haemost . 1999;81:758-762.

Moore GW , Smith MP , Patel Y. , et al. The Activated Seven Lupus Anticoagulant (ASLA) assay: a new test for lupus anticoagulants (LAs). Evidence that some LAs are detectable only in extrinsic pathway based assays. Blood Coagul Fibrinolysis . 2002;13:261-269.

Jennings I. , Kitchen S. , Woods TA , et al. Potentially clinically important inaccuracies in testing for the lupus anticoagulant: an analysis of results from three surveys of the UK National External Quality Assessment Scheme (NEQAS) for blood coagulation . Thromb Haemost. 1997;77:934-937.

Brandt JT , Triplett DA , Alving B. , et al. Criteria for the diagnosis of lupus anticoagulants: an update . Thromb Haemost. 1995;74:1185-1190.

Greaves M. , Cohen H. , Machin SJ , et al. Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol. 2000;109:704-715.

Greaves M. Antiphospholipid syndrome. J Clin Pathol. 1997;50:973-974.

10.

Lillicrap DP , Pinto M. , Benford K. , et al. Heterogeneity of laboratory test results for antiphospholipid antibodies in patients treated with chlorpromazine and other phenothiazines. Am J Clin Pathol. 1990 ;93:771-775.

11.

Male C. , Lechner K. , Eichinger S. , et al. Clinical significance and course of lupus anticoagulants in children. J Pediatr. 1999;134:199-205.

12.

Miyakis S. , Lockshin MD , Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295-306.

13.

Machin SJ , Giddings JC , Greaves M. , et al. Guidelines on testing for the lupus anticoagulant. J Clin Pathol. 1991;44:885-889.

14.

Moore GW , Smith MP , Savidge GF The Ecarin time is an improved confirmatory test for the Taipan snake venom time in warfarinised patients with lupus anticoagulants. Blood Coagul Fibrinolysis. 2003;14:307-312.

15.

Gardiner C. , Mackie IJ , Malia RG , et al. The importance of locally derived reference ranges and standardised calculation of dilute Russell's viper venom time results in screening for lupus anticoagulant. Br J Haematol . 2000; 111:1230-1235.

16.

Galli M. , Luciani D. , Bertolini G. , et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003;101: 1827-1832.

17.

Brouwer JL , Bijl M. , Veeger NJ , et al. The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus. Blood. 2004;104:143-148.

18.

Calvo-Alen J. , Toloza SM , Fernandez M. , et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients. Arthritis Rheum. 2005;52:2060-2068.

19.

Somers E. , Magder LS , Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol . 2002;29:2531-2536.

20.

Male C. , Foulton D. , Hoogendoorn H. , et al. Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in paediatric patients with systemic lupus erythematosus. Blood. 2005;106:4152-4158.

21.

Schjetlein R. , Wisløff F. An evaluation of two commercial test procedures for the detection of lupus anticoagulant. Am J Clin Pathol . 1995;103:108-111.

22.

Martinuzzo M. , Adamczuk Y. , Iglesias Varela ML , et al. The Activated Seven Lupus Anticoagulant (ASLA) test has comparable sensitivity to classical assays for screening of lupus anticoagulant. Thromb Haemost . 2005;93:1007-1009.

23.

Arnout J. , Vermylen J. Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic disease. J Thromb Haemost. 2003;1:931-942.

24.

Pengo V. , Biasiolo A. , Pegoraro C. , et al. A two-step coagulation test to identify antiβ2-glycoprotein I lupus anticoagulants. J Thromb Haemost. 2004;2:702-707.

25.

de Laat HB , Derksen RH , Urbanus RT , et al. β2-glycoprotein I-dependent lupus anticoagulant activity highly correlates with thrombosis in the antiphospholipid syndrome. Blood. 2004;104:3598-3602.

26.

Le Querrec A. , Arnout J. , Arnoux D. , et al. Quantification of lupus anticoagulants in clinical samples using antiβ2GPI and anti-prothrombin monoclonal antibodies . Thromb Haemost. 2001;86:584-589.

27.

Arnout J. , Wittevrongel C. , Vanrusselt M. , et al. Beta-2-glycoprotein I dependent lupus anticoagulants form stable bivalent antibody Beta-2-Glycoprotein I complexes on phospholipid surfaces . Thromb Haemost. 1998;79:79-86.

28.

Simmelink MJ , Horbach DA , Derksen RH , et al. Complexes of anti-prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces. Br J Haematol. 2001;113:621-629.

29.

Willems GM , Janssen MP , Pelsers MM , et al. Role of divalency in the high-affinity binding of anticardiolipin antibody-β2-glycoprotein I complexes to lipid membranes. Biochemistry 1996;35:13833-13842.

30.

Bidot CJ , Jy W. , Horstman LL , et al. Factor VII/VIIa: a new antigen in the anti-phospholipid antibody syndrome. Br J Haematol. 2003;120:618-626.

31.

Wahl DG , Guillemin F. , de Maistre E. , et al. Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus. 1998;7: 15-22.

32.

Wahl DG , Bounameaux H. , de Moerloose P. , et al. Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus with or without antiphospholipid antibodies: do the benefits outweigh the risks? A decision analysis. Arch Intern Med. 2000;160:2042-2048.