Relative Sensitivity of Different Tests in the Detection of Low Titer Lupus Anticoagulants

Summary

Lupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.

Keywords

Lupus anticoagulant - Coagulation factor assays - Anticardiolipin antibodies - Thrombosis - Fetal loss

• References

• 1 Thiagarajan P, Shapiro SS, De MarcoL. Monoclonal immunoglobulin M coagulation inhibitor with phospholipid specificity: mechanism of a lupus anticoagulant. J Clin Invest 1980; 66: 397-405
• 2 Feinstein DI, Rapaport SI. Acquired inhibitors of blood coagulation. Prog Hemostas Thromb 1972; 1: 75-95
• 3 Conley CL, Hartmann RC. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952; 31: 621-622
• 4 Schleider MA, Nachman RL, Jaffe EA, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976; 499-509
• 5 Shapiro SS, Thiagarajan P. Lupus anticoagulant. Prog Hemostasis Thromb 1982; 6: 263-285
• 6 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. A study of 25 cases and review of the literature. Haemostasis 1985; 15: 254-262
• 7 Gordlund B. The lupus inhibitor in thromboembolic disease and intrauterine death in the absence of systemic lupus. Acta Med Scand 1984; 215: 293-298
• 8 Feinstein DI. Lupus anticoagulant, thrombosis and fetal loss. N Engl J Med 1985; 313: 1348-1350
• 9 Lubbe WF, Liggins GC. Lupus anticoagulant and pregnancy. Am J Obstet Gynecol 1985; 153: 322-327
• 10 Lubbe WF, Butler WS, Palmer SJ, Liggins GC. Lupus anticoagulant in pregnancy. Br J Obstet Gynecol 1984; 91: 357-363
• 11 Branch DW, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med 1985; 313: 1322-1326
• 12 Harris EN, Loizou S, Englert H, Derue G, Chan JK, Gharavi AE, Hughs GRV. Anticardiolipin antibodies and lupus anticoagulant. Lancet 1984; 2: 1099
• 13 Harris EN, Gharavi AE, Boly ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GRV. Anticardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1213
• 14 Loizou S, Mc Créa JD, Rudge AC, Reynolds R, Boyle CC, Harris EN. Measurement of anticardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA); standardisation and quantitation of, results. Clin Exp Immunol 1985; 62: 738-745
• 15 Lockshin M, Druzin ML, Goli S, Qamar T, Magig MS, Jovanovic L, Ferenc M. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med 1985; 313: 152-156
• 16 Hazeltine M, Rauch J, Danoff D, Esdaile JM, Tannenbaum H. Antiphospholipid antibodies in systemic lupus erythematosus: Evidence of an association with positive Coomb’s and hypocomplementenna. J Rheumatol 1988; 15: 80-86
• 17 Green D, Hougie C, Kazmier FJ, Lechner K, Mannucci P, Rizza CR, Sultan Y. Report of the working party on acquired inhibitors of coagulation: studies of the “lupus” anticoagulant. Thromb Haemostas 1983; 49: 144-146
• 18 Exner T, Richard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioral pattern. Br J Haematol 1978; 40: 143-151
• 19 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venon time for the diagnosis of lupus anticoagulants. Blood 1986; 68: 869-874
• 20 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
• 21 Triplett DA, Brandt JT, Kaczor D, Schaeffer J. Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibitor procedure with a new platelet neutralization procedure. Am J Clin Pathol 1983; 79: 678-682
• 22 Elashoff JD. Analysis of repeated measures designs, BMDP Tech Rep No. 83. 1986
• 23 Fleiss JL. The Design and Analysis of Clinical Experiments. John Wiley & Sons; New York : 1986
• 24 Makie IJ, Colaco CB, Machin SJ. Familial lupus anticoagulants. Br J Haematol 1987; 67: 359-363
• 25 Lockwood CJ, Reece EA, Romero R, Hobbins JC. Antiphospholipid antibody and pregnancy wastage. Lancet 1986; 2: 742-743
• 26 Petri M, Rheinschmidt M, Whiting-O’Keefe Q, Hellmann D, Corash L. The frequency of lupus anticoagulant in systemic lupus erythematosus. A study of sixty consecutive patients by activated partial thromboplastin time. Russell viper venom time and anticardiolipin antibody level. Ann Intern Med 1987; 106: 524-531
• 27 Lafer EM, Rauch J, Andrzejwski C, Mudd D, Furie B, Schwartz RS, Stollar D. Polyspecific monoclonal lupus antibodies reactive with both polynucleotides and phospholipids. J Exp Med 1981; 153: 897-909
• 28 Tannenbaum M, Rauch J, Ramelson H, Cullis PR, Tilcock CPS, Hope MJ, Janoff AS. Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid system. J Biol Chem 1986; 261: 9672-9677