Download PDF
Thromb Haemost 1995; 74(06): 1597-1603
DOI: 10.1055/s-0038-1649988
Scientific and Standardization Committee Communication
Schattauer GmbH Stuttgart

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
John T Brandt
1   The Department of Pathology, Ohio State University, Columbus, OH, USA
,
Linda K Barna
2   The Department of Pathology, Ball Memorial Hospital, Muncle, IN, USA
,
Douglas A Triplett
2   The Department of Pathology, Ball Memorial Hospital, Muncle, IN, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
10 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Lupus anticoagulants (LAs) are antibodies that interfere with phospholipid dependent coagulation reactions in vitro. This workshop was designed to provide the participants with an experience in identification of LAs, to evaluate different criteria for mixing studies, to assess the performance of recently introduced confirmatory studies and to assess the performance of two potential surrogate LA control plasmas. The results demonstrate that there continues to be significant variation in the sensitivity and responsiveness of APTT reagents to the presence of LAs, confirming the need for more than one screening assay before the presence of a LA can be ruled out. In this workshop, the best distinction between factor deficiency and inhibitors was obtained using a 1:1 mix of normal plasma with patient plasma and the criterion defining correction as shortening of the APTT to within 5 s of the APTT of pooled normal plasma. A 4:1 mix of patient to normal plasma did not work well in distinguishing factor deficiency from inhibitors. The platelet neutralization procedure, DVVconfirm® and StaClot LA® all gave positive results with the LA samples. False positive platelet neutralization procedures were seen with the samples from patients on oral anticoagulants and a factor V inhibitor. False positive StaClot LA results were obtained with high titer factor VIII inhibitors. Both of the potential surrogate plasmas gave variable results with multiple assays; they can not be recommended for routine use at present.

 

  • References

  • 1 Triplett DA, Brandt JT. Laboratory identification of the lupus anticoagulant. Br J Haematol 1989; 73: 139-142
    CrossrefPubMedSearch in Google Scholar
  • 2 Bevers EM, Galli M, Barbui T, Comfurious P, Zwaal RF A. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629-632
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Oosting JD, Derksen RH W M, Bobbink IW G, Hackeng TM, Bouma BN, deGroot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism. Blood 1993; 81: 2618-2625
    PubMedSearch in Google Scholar
  • 4 Galli M, Beguin S, Lindhout T, Hemker CH. Inhibition of phospholipid and platelet-dependent prothrombinase activity in the plasma of patients with lupus anticoagulants. Br J Haematol 1989; 72: 549-555
    CrossrefPubMedSearch in Google Scholar
  • 5 McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193-280
    PubMedSearch in Google Scholar
  • 6 Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Ann Intern Med 1990; 112: 682-698
    CrossrefPubMedSearch in Google Scholar
  • 7 Harris EN. Antiphospholipid antibodies. Br J Haematol 1990; 74: 1-9
    PubMedSearch in Google Scholar
  • 8 Triplett DA. Antiphospholipid-protein antibodies: laboratory diagnosis and clinical relevance. Thromb Res 1995; 78: 1-31
    CrossrefPubMedSearch in Google Scholar
  • 9 Mueh JR, Herbst KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Int Med 1980; 92: 156-159
    CrossrefPubMedSearch in Google Scholar
  • 10 Nilsson IM, Astedt B, Hedner U, Berezin D. Intrauterine death and circulating anticoagulant, “antithromboplastin”. Acta Med Scand 1975; 197: 153-159
    PubMedSearch in Google Scholar
  • 11 Levine SR, Welch KM A. The spectrum of neurologic disease associated with antiphospholipid antibodies: lupus anticoagulants and anticardiolipin antibodies. Arch Neurol 1987; 44: 876-883
    CrossrefPubMedSearch in Google Scholar
  • 12 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. A study of 25 cases and review of the literature Haemost 1985; 15: 254-262
    CrossrefPubMedSearch in Google Scholar
  • 13 Exner T, Triplett DA, Tabemer D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost 1991; 65: 320-322
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Lupus Anticoagulant Working Parly. Guidelines on testing for the lupus anticoagulant J Clin Pathol 1991; 44: 885-889
    CrossrefPubMed
  • 15 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom lime lor (he diagnosis of lupus anticoagulants. Blood 1986; 68: 869-874
    PubMedSearch in Google Scholar
  • 16 Triplett DA, Brandt JT, Kaczor D, Schaeffer J. Laboratory diagnosis of lupus inhibitors. A comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure Am J Clin Pathol 1983; 79: 678-682
    CrossrefPubMedSearch in Google Scholar
  • 17 Triplett DA, Barna LK, Unger GA. A hexagonal (II) phase phospholipid neutralization assay for lupus anticoagulant identification. Thromh Haemost 1993; 70: 787-793
    PubMedSearch in Google Scholar
  • 18 Uchman B, Triplett DA. Inhibitor effect of polymyxin B on the X-ase and prothrombinase complex formation. Thromb Haemost 1989; 62: 375 (abstract)
    PubMedSearch in Google Scholar
  • 19 McGlasson DL, Babeock JL, Berg L, Triplett DA. ARACHnasc; an evaluation of a positive control for platelet neutralization procedure testing with seven commercial activated partial thromboplastin time reagents. Am J Clin Pathol 1993; 100: 576-578
    CrossrefPubMedSearch in Google Scholar
  • 20 Rosner E, Pauzner R, Lusky A, Modan M, Many A. Detection and quantitative evaluation of lupus circulating anticoagulant activity. Thromb Haemost 1987; 57: 144-147
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Kasper CK. Laboratory tests for factor VIII inhibitors, their variation, significance and interpretation. Blood Coag Fibrinol 1991; 2 Suppl (Suppl. 01) 7-10
    CrossrefPubMedSearch in Google Scholar
  • 22 Triplett DA, Brandt JT, Maas RL. The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med 1985; 109: 946-951
    PubMedSearch in Google Scholar
  • 23 Brandt JT, Britton A, Kraut EA. Spontaneous factor V inhibitor with unexpected laboratory features. Arch Pathol Lab Med 1986; 110: 224-227
    PubMedSearch in Google Scholar
  • 24 Brandt JT, Triplett DA, Musgrave K, Orr CA. The sensitivity of different coagulation reagents to the presence of lupus anticoagulants. Arch Pathol Lab Med 1987; 111: 120-124
    PubMedSearch in Google Scholar
  • 25 Adcock DM, Marlar RA. Activated partial thromboplastin time reagent sensitivity to the presence of lupus anticoagulants. Arch Pathol Lab Med 1992; 116: 837-840
    PubMedSearch in Google Scholar
  • 26 Hemostasis Committee of the “Societè Francaise de Biologie Clinique”: Laboratory heterogencity of the lupus anticoagulant, a multicenlrc study using different clotting assays on a panel of 78 samples. Thromb Res 1992; 66: 349-364
    CrossrefPubMed
  • 27 Forastiero RR, Cerrato GS, Carreras LO. Evaluation of recently described tests for detection of the lupus anticoagulant. Thromb Haemost 1994; 72: 728-733
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Johns AS, Chamley L, Ockelford PA, Pattison NS, McKay EJ, Corkill M, Hart H. Comparison of tests for the lupus anticoagulant and antiphospholipid antibodies in systemic lupus erythematosus. Clin Exper Rheumatol 1994; 12: 523-526
    PubMedSearch in Google Scholar
  • 29 Kaczor DA, Bickford NN, Triplett DA. Evaluation of different mixing study reagents and dilution effect in lupus anticoagulant testing. Am J Clin Pathol 1991; 95: 408-411
    CrossrefPubMedSearch in Google Scholar
  • 30 Clyne LP, White PF. Time dependency of lupus-like anticoagulants. Arch hit Med 1988; 148: 1060-1063
    PubMedSearch in Google Scholar
  • 31 Lazarchick J, Kizer J. The laboratory diagnosis of lupus anticoagulants. Arch Pathol Lab Med 1989; 113: 177-180
    PubMedSearch in Google Scholar
  • 32 Rauch J, Tannenbaum M, Tannenbaum H, Ramelson H, Cullis PR, Tilcock CP S, Hope MJ, Janoff AS. Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems. J Biol Chcm 1986; 261: 9672-9677
    PubMedSearch in Google Scholar
  • 33 Rauch J, Tannenbaum M, Janoff AS. Distinguishing plasma lupus anticoagulants from anti-factor antibodies using Hexagonal(II) phase phospholipids. Thromb Haemost 1989; 62: 892-896
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Ballard HS, Nyamuswa G. Life-threatening haemorrhage in a patient with rheumatoid arthritis and a lupus anticoagulant coexisting with acquired autoantibodies against factor VIII. Br J Rheumatol 1993; 32: 515-517
    CrossrefPubMedSearch in Google Scholar