Download PDF
Thromb Haemost 2000; 83(05): 704-708
DOI: 10.1055/s-0037-1613896
Review Article
Schattauer GmbH

The Lupus Ratio Test – An Interlaboratory Study on the Detection of Lupus Anticoagulants by an APTT-based, Integrated, and Semi-quantitative Test

From the Fifth International Survey of Lupus Anticoagulants - ISLA 5
E. M. Jacobsen
1   From the Haematological Research Lab., Medical Clinic, Ullevål University Hospital, Oslo, Norway
,
L. Barna-Cler
2   Midwest Hemostasis and Thrombosis Laboratory, Ball Memorial Hospital, Muncie, IN, USA
,
J. M. Taylor
2   Midwest Hemostasis and Thrombosis Laboratory, Ball Memorial Hospital, Muncie, IN, USA
,
D. A. Triplett
2   Midwest Hemostasis and Thrombosis Laboratory, Ball Memorial Hospital, Muncie, IN, USA
,
F. Wisløff
1   From the Haematological Research Lab., Medical Clinic, Ullevål University Hospital, Oslo, Norway
› Author Affiliations
Further Information

Publication History

Received 30 June 1999

Accepted after resubmission 17 December 1999

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The Lupus Ratio (LR) test for lupus anticoagulants integrates screening, mixing with normal plasma and confirmation procedures into one assay. The sensitivity and reproducibility of the APTT based version of this assay was tested in an interlaboratory study that was part of the Fifth International Survey of Lupus Anticogulants (ISLA-5).

One LA negative plasma containing heparin, six LA positive plasmas and a normal pooled plasma (NP) were distributed to 31 laboratories world-wide together with two APTT reagents, one with a high and one with a low phospholipid concentration. The laboratories performed two APTTs, one with each reagent, on 1 : 1 mixtures of test plasma and NP. The ratio between the two clotting times was divided by the corresponding ratio for the NP. This final ratio is the LR of that plasma. The overall sensitivity was found to be 95.1%, and the normal, heparin-containing sample was reported to be negative by all the laboratories.

When the results were grouped in low, medium and high positive plasmas, a “consensus” regarding the strength of each plasma was easily found. 85.0% of the results were in agreement with this consensus.

This study shows that with the LR test, it is possible to obtain high interlaboratory agreement regarding the presence or absence of LA as well as the semi-quantification of this inhibitor.

Appendix, please see p. 708.

Keywords

Lupus anticoagulants - activated partial thromboplastin time (APTT) - reproducibility of results
 

  • References

  • 1 McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-Glycoprotein I (apolipoprotein H). Proc Natl Acad Sci 1990; 87: 4120-4.
    CrossrefPubMedGoogle Scholar
  • 2 Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van BredaVriesman PJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-7.
    CrossrefPubMedGoogle Scholar
  • 3 Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RFA. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66 (06) 629-32.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Vermylen J, Arnout J. Is the antiphospholipid syndrome caused by antibodies directed against physiologically relevant phospholipid-protein complexes?. J Lab Clin Med 1992; 120 (01) 10-2.
    PubMedGoogle Scholar
  • 5 Triplett DA. Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. Thromb Res 1995; 78 (01) 1-31.
    CrossrefPubMedGoogle Scholar
  • 6 Machin SJ, Giddings JC, Greaves M, Hutton RA, Mackie IJ, Malia RG, Taberner DA. Guidelines on testing for the lupus anticoagulant. Lupus Anticoagulant Working Party on behalf of the BCSH Haemostasis and Thrombosis Task Force. J Clin Pathol 1991; 44: 885-9.
    CrossrefPubMedGoogle Scholar
  • 7 Brandt JT, Triplett DA, Alving B, Scharrer I. 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 (04) 1185-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Jacobsen EM, Wislcff F. False negative screening tests for lupus anticoagulants – an unrecognized problem?. Thromb Res 1996; 82 (05) 445-51.
    CrossrefPubMedGoogle Scholar
  • 9 Hemostasis Committee of the “Societe Francaise de Biologie Clinique”. Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Thromb Res 1992; 66 (04) 349-64.
    CrossrefPubMedGoogle Scholar
  • 10 Peaceman AM, Silver RK, MacGregor SN, Socol ML. Interlaboratory variation in antiphospholipid antibody testing. Am J Obstet Gynecol 1992; 166 (06) 1780-4.
    CrossrefPubMedGoogle Scholar
  • 11 Roussi J, Roisin JP, Goguel A. Lupus anticoagulants. First French Interlaboratory Etalonorme Survey. Am J Clin Pathol 1996; 105 (06) 788-93.
    CrossrefPubMedGoogle Scholar
  • 12 Jennings I, Kitchen S, Woods TAL, Preston FE, Greaves M. 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 (05) 934-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Schjetlein R, Sletnes KE, Wislcff F. A quantitative, semi-automated and computer-assisted test for lupus anticoagulant. Thromb Res 1993; 69 (02) 239-50.
    CrossrefPubMedGoogle Scholar
  • 14 Rosner E, Pauzner R, Lusky A, Modan M, Many A. Detection and quantitative evaluation of lupus circulating anticoagulant activity. Thromb Haemost 1987; 57 (02) 144-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Speck R. New method for quantifying lupus anticoagulant. Clin Appl Thrombosis/Hemostasis 1996; 02 (04) 237-40.
    CrossrefPubMedGoogle Scholar
  • 16 Exner T, Triplett DA, Taberner DA, Machin SJ. Scientific and Standardization Committee Communications. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost 1991; 65 (03) 320-2.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Schjetlein R, Wislcff F. An evaluation of two commercial test procedures for the detection of lupus anticoagulant. Am J Clin Pathol 1995; 103 (01) 108-11.
    CrossrefPubMedGoogle Scholar
  • 18 Exner T, Triplett DA, Taberner DA, Howard MA, Harris EN. Scientific and Standardization Committee Communications. Comparison of test methods for the lupus anticoagulant: International survey on lupus anticoagulants-I (ISLA-1). Thromb Haemost 1990; 64 (03) 478-84.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Brandt JT, Barna LK, Triplett DA. Laboratory identification of lupus anticoagulants: results of the Second International Workshop for Identification of Lupus Anticoagulants. On behalf of the Subcommittee on Lupus Anticoagulants/Antiphospholipid Antibodies of the ISTH. Thromb Haemost 1995; 74 (06) 1597-603.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Brandt JT, Triplett DA, Musgrave K, Orr C. The sensitivity of different coagulation reagents to the presence of lupus anticoagulants. Arch Pathol Lab Med 1987; 111: 120-4.
    PubMedGoogle Scholar
  • 21 Arnout J, Vanrusselt M, Wittevrongel C, Vermylen J. Monoclonal antibodies against beta-2-glycoprotein I: use as reference material for lupus anticoagulant tests. Thromb Haemost 1998; 79 (05) 955-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Oosting JD, Derksen RHWM, Entjes HTI, Bouma BN, de Groot PG. Lupus anticoagulant activity is frequently dependent on the presence of β2-glycoprotein I. Thromb Haemost 1992; 67 (05) 499-502.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Ogasawara M, Aoki K, Matsuura E, Sasa H, Yagami Y. Anti β2glycoprotein I antibodies and lupus anticoagulant in patients with recurrent pregnancy loss: prevalence and clinical significance. Lupus 1996; 5 (06) 587-92.
    CrossrefPubMedGoogle Scholar
  • 24 Triplett DA. Coagulation assays for the lupus anticoagulant: Review and critique of current methodology. Stroke. 1992 23. Suppl. I I-11-I-14.
    PubMedGoogle Scholar