Comparison Between a One-Point Dilute Phospholipid APTT and the Dilute Russell Viper Venom Time for Verification of Lupus Anticoagulants

Summary

In the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RWT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of ≥1.3 for the PL-APTT with liposomes and ≥1.2 for the PL-APTT with Thrombofax and the RWT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RWT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies.

• References

• 1 Thiagarajan P, Shapiro SS, DeMarco L. Monoclonal immunoglobulin M ^-coagulation inhibitor with phospholipid specificity: mechanism of a lupus anticoagulant. J Clin Invest 1980; 66: 397-405
• 2 Alving BM, Banerji B, Fogler WE, Alving CR. Lupus anticoagulant activities of murine monoclonal antibodies to liposomal phosphatidyl inositol phosphate. Clin Exp Immunol 1987; 69: 403-408
• 3 Exner T, Triplett DA, Taberner D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC subcommittee for the standardization of lupus anticoagulants. Thromb Haemostas 1991; 65: 320-322
• 4 Harris EN, Asherson RA, Hughes GRV. Antiphospholipid anti-bodies-autoantibodies with a difference. Annu Rev Med 1988; 39: 261-271
• 5 Alving BM, Barr CF, Tang DB. Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times. Am J Med 1990; 88: 112-116
• 6 Harris EN. Annotation: antiphospholipid antibodies. Br J Haematol 1990; 74: 1-9
• 7 Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med 1990; 112: 682-698
• 8 Sammaritano LR, Gharavi AE, Lockshin MD. Antiphospholipid antibody syndrome: immunologic and clinical aspects. Sem Arthritis Rheum 1990; 20: 81-96
• 9 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
• 10 Rosove MH, Ismail M, Koziol BJ, Runge A, Kasper CK. Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations. Blood 1986; 68: 472-478
• 11 Alving BM, Baldwin PE, Richards RL, Jackson BJ. The dilute phospholipid APTT: a sensitive assay for verification of lupus anticoagulants. Thromb Haemostas 1985; 54: 709-712
• 12 Exner T. Comparison of two simple tests for the lupus anticoagulant. Am J Clin Pathol 1985; 83: 215-218
• 13 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 1986; 68: 869-874
• 14 Exner T, Papadopoulos G, Koutts J. Use of a simplified dilute Russell’s viper venom time (DRWT) confirms heterogeneity among “lupus anticoagulants”. Blood Coagul Fibrinol 1990; 1: 259-266
• 15 Exner T, Triplett DA, Taberner DA, Howard MA, Harris EN. Comparison of test methods for the lupus anticoagulant: international survey on lupus anti-coagulants-I (ISLA-1). Thromb Haemostas 1990; 64: 478-484
• 16 Triplett DA, Brandt JT, Musgrave KA, Orr CA. The relationship between lupus anticoagulants and antibodies to phospholipid. JAMA 1988; 259: 550-554
• 17 O’Leary DS, Ruymann FB, Conrad ME. Therapeutic approaches to factor X deficiency with emphasis on the use of a new clotting factor concentrate (Konyne). J Lab Clin Med 1971; 77: 23-32
• 18 Clyne LP, White PF. Time dependency of lupuslike anticoagulants. Arch Intern Med 1988; 148: 1060-1063
• 19 Triplett DA, Brandt JT, Maas RL. The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med 1985; 109: 946-951
• 20 Kasper CK, Aledort LM, Counts RB. et al A more uniform measurement of Factor VIII inhibitors. Thromb Diathes Haemorrh (Stuttg) 1975; 34: 869-872
• 21 Harris EN. The second international anti-cardiolipin standardization workshop. The Kingston Anti-Phospholipid Antibody Study (KAPS) Group. Am J Clin Pathol 1990; 94: 476-484
• 22 Dixon WJ, Massey Jr FJ. Introduction to Statistical Analysis. McGraw-Hill Book Co., Inc.; New York: 2nd ed. 1957. pp 174-176
• 23 Griner PF, Mayewski RJ, Mushlin AI, Greenland P. Selection and interpretation of diagnostic tests and procedures. Principles and applications. Ann Intern Med 1981; 94: 553-570
• 24 Hanely JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143: 29-36
• 25 Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemostas 1990; 16: 1-20
• 26 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: 120-124
• 27 Kitchens CS. Prolonged activated partial thromboplastin time of unknown etiology: a prospective study of 100 consecutive cases referred for consultation. Am J Clin Pathol 1988; 27: 38-45
• 28 Galli M, Comfurius P, Maassen C, Hemker HC, deBaets MH, van Breda-Vriesman PJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-1547
• 29 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: (3₂-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120-4124
• 30 Exner T, Sahman N, Trudinger B. Separation of anticardiolipin antibodies from lupus anticoagulant on a phospholipid-coated polystyrene column. Biochem Biophys Res Commun 1988; 155: 1001-1007
• 31 McNeil HP, Chesterman CN, Krilis SA. Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics. Br J Haematol 1989; 73: 506-513
• 32 McNeil HP, Chesterman CN, Krilis SA. Binding specificity of lupus anticoagulants and anticardiolipin antibodies. Thromb Res 1988; 52: 609-619
• 33 Rauch J, Tannenbaum M, Tannenbaum H, Ramelson H, Cullis PR, Tilcock CPS, Hope NJ, Janoff AS. Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems. J Biol Chem 1986; 261: 9672-9677