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. 1992 Apr;45(4):332–338. doi: 10.1136/jcp.45.4.332

Methods for detecting lupus anticoagulants and their relation to thrombosis and miscarriage in patients with systemic lupus erythematosus.

D Ferro 1, M Saliola 1, C Quintarelli 1, G Valesini 1, S Basili 1, A M Grandilli 1, M S Bonavita 1, F Violi 1
PMCID: PMC495275  PMID: 1577971

Abstract

AIMS: To examine the sensitivity and specificity to past thrombotic events of four different coagulation tests, which screen for lupus anticoagulant (LA), and of anticardiolipin antibodies in patients with systemic lupus erythematosus. METHODS: Fifty three consecutive patients with systemic lupus erythematosus were studied of whom three males and 21 females, aged 21-60 years, had a history of venous and arterial thrombosis, or miscarriage, or both. Activated partial thromboplastin time (aPTT), dilute Russell's viper venom time (dRVVT), kaolin clotting time (KCT), dilute aPTT and the circulating titre of anticardiolipin antibodies were investigated in the two groups of patients and in 20 healthy control subjects. RESULTS: The prolonged dilute aPTT was more sensitive to thromboses or miscarriages, or both than dRVVT (p less than 0.05), KCT (p less than 0.01), and aPTT (p less than 0.001). No significant differences in specificity were found among aPTT (100%), dRVVT (93%), KCT (93%) and dilute aPTT (86.2%); but aPTT and dRVVT were significantly more specific (p less than 0.01, p less than 0.05, respectively) than anticardiolipin antibodies. CONCLUSIONS: The study shows a strong association between lupus anticoagulant and thrombosis when a very sensitive test such as the dilute aPTT is used. The combination of this assay with a very specific test such as dRVVT might enable patients with SLE at high risk of thrombosis to be identified.

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Selected References

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  1. Alving B. M., Baldwin P. E., Richards R. L., Jackson B. J. The dilute phospholipid APTT: a sensitive assay for verification of lupus anticoagulants. Thromb Haemost. 1985 Oct 30;54(3):709–712. [PubMed] [Google Scholar]
  2. Alving B. M., Barr C. F., Tang D. B. Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times. Am J Med. 1990 Feb;88(2):112–116. doi: 10.1016/0002-9343(90)90458-p. [DOI] [PubMed] [Google Scholar]
  3. Angles-Cano E., Sultan Y., Clauvel J. P. Predisposing factors to thrombosis in systemic lupus erythematosus: possible relation to endothelial cell damage. J Lab Clin Med. 1979 Aug;94(2):312–323. [PubMed] [Google Scholar]
  4. Boey M. L., Colaco C. B., Gharavi A. E., Elkon K. B., Loizou S., Hughes G. R. Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. Br Med J (Clin Res Ed) 1983 Oct 8;287(6398):1021–1023. doi: 10.1136/bmj.287.6398.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Branch D. W. Immunologic disease and fetal death. Clin Obstet Gynecol. 1987 Jun;30(2):295–311. doi: 10.1097/00003081-198706000-00009. [DOI] [PubMed] [Google Scholar]
  6. Brandt J. T., Triplett D. A., Musgrave K., Orr C. The sensitivity of different coagulation reagents to the presence of lupus anticoagulants. Arch Pathol Lab Med. 1987 Feb;111(2):120–124. [PubMed] [Google Scholar]
  7. Brandt J. T., Triplett D. A., Rock W. A., Bovill E. G., Arkin C. F. Effect of lupus anticoagulants on the activated partial thromboplastin time. Results of the College of American Pathologists survey program. Arch Pathol Lab Med. 1991 Feb;115(2):109–114. [PubMed] [Google Scholar]
  8. Canoso R. T., Sise H. S. Chlorpromazine-induced lupus anticoagulant and associated immunologic abnormalities. Am J Hematol. 1982 Sep;13(2):121–129. doi: 10.1002/ajh.2830130204. [DOI] [PubMed] [Google Scholar]
  9. Cohen A. J., Philips T. M., Kessler C. M. Circulating coagulation inhibitors in the acquired immunodeficiency syndrome. Ann Intern Med. 1986 Feb;104(2):175–180. doi: 10.7326/0003-4819-104-2-175. [DOI] [PubMed] [Google Scholar]
  10. Derksen R. H., Bouma B. N., Kater L. The striking association between lupus anticoagulant and fetal loss in systemic lupus erythematosus patients. Arthritis Rheum. 1986 May;29(5):695–696. doi: 10.1002/art.1780290520. [DOI] [PubMed] [Google Scholar]
  11. Derksen R. H., Hasselaar P., Blokzijl L., Gmelig Meyling F. H., De Groot P. G. Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients. Ann Rheum Dis. 1988 May;47(5):364–371. doi: 10.1136/ard.47.5.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Derksen R. H., Kater L. Lupus anticoagulant: revival of an old phenomenon. Clin Exp Rheumatol. 1985 Oct-Dec;3(4):349–357. [PubMed] [Google Scholar]
  13. Exner T. Comparison of two simple tests for the lupus anticoagulant. Am J Clin Pathol. 1985 Feb;83(2):215–218. doi: 10.1093/ajcp/83.2.215. [DOI] [PubMed] [Google Scholar]
  14. Exner T., McRea J. Studies on the relationship between 'antiphospholipid' antibodies and the lupus anticoagulant. Blood Coagul Fibrinolysis. 1990 Mar-Apr;1(1):17–21. doi: 10.1097/00001721-199003000-00004. [DOI] [PubMed] [Google Scholar]
  15. Exner T., Papadopoulos G., Koutts J. Use of a simplified dilute Russell's viper venom time (DRVVT) confirms heterogeneity among 'lupus anticoagulants'. Blood Coagul Fibrinolysis. 1990 Aug;1(3):259–266. doi: 10.1097/00001721-199008000-00002. [DOI] [PubMed] [Google Scholar]
  16. Exner T., Rickard K. A., Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol. 1978 Sep;40(1):143–151. doi: 10.1111/j.1365-2141.1978.tb03648.x. [DOI] [PubMed] [Google Scholar]
  17. Exner T., Triplett D. A., Taberner D., Machin S. J. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost. 1991 Mar 4;65(3):320–322. [PubMed] [Google Scholar]
  18. FRICK P. G. Acquired circulating anticoagulants in systemic collagen disease; auto-immune thromboplastin deficiency. Blood. 1955 Jul;10(7):691–706. [PubMed] [Google Scholar]
  19. Feinstein D. I., Rapaport S. I. Acquired inhibitors of blood coagulation. Prog Hemost Thromb. 1972;1:75–95. [PubMed] [Google Scholar]
  20. Ferro D., Saliola M., Quintarelli C., Carlucci M., Valesini G., Violi F. Specificity and sensitivity of diluted aPTT and anticardiolipin antibodies towards thrombosis and miscarriages in patients with systemic lupus erythematosus. Thromb Res. 1990 Aug 1;59(3):609–617. doi: 10.1016/0049-3848(90)90419-d. [DOI] [PubMed] [Google Scholar]
  21. Gastineau D. A., Kazmier F. J., Nichols W. L., Bowie E. J. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985 Jul;19(3):265–275. doi: 10.1002/ajh.2830190308. [DOI] [PubMed] [Google Scholar]
  22. Glueck H. I., Kant K. S., Weiss M. A., Pollak V. E., Miller M. A., Coots M. Thrombosis in systemic lupus erythematosus. Relation to the presence of circulating anticoagulants. Arch Intern Med. 1985 Aug;145(8):1389–1395. [PubMed] [Google Scholar]
  23. Harris E. N., Chan J. K., Asherson R. A., Aber V. R., Gharavi A. E., Hughes G. R. Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test. Arch Intern Med. 1986 Nov;146(11):2153–2156. [PubMed] [Google Scholar]
  24. Harris E. N., Gharavi A. E., Boey M. L., Patel B. M., Mackworth-Young C. G., Loizou S., Hughes G. R. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet. 1983 Nov 26;2(8361):1211–1214. doi: 10.1016/s0140-6736(83)91267-9. [DOI] [PubMed] [Google Scholar]
  25. Harris E. N., Loizou S., Englert H., Derue G., Chan J. K., Gharavi A. E., Hughes G. R. Anticardiolipin antibodies and lupus anticoagulant. Lancet. 1984 Nov 10;2(8411):1099–1099. doi: 10.1016/s0140-6736(84)91537-x. [DOI] [PubMed] [Google Scholar]
  26. Harris E. N. Solid-phase anti-cardiolipin test revisited. Am J Med. 1988 Nov;85(5):599–601. doi: 10.1016/0002-9343(88)90678-x. [DOI] [PubMed] [Google Scholar]
  27. Hughes G. R., Harris N. N., Gharavi A. E. The anticardiolipin syndrome. J Rheumatol. 1986 Jun;13(3):486–489. [PubMed] [Google Scholar]
  28. Hughes G. R. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J (Clin Res Ed) 1983 Oct 15;287(6399):1088–1089. doi: 10.1136/bmj.287.6399.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Jungers P., Liote F., Dautzenberg M. D., Gazengel C., Dougados M., Tron F., Bach J. F. Lupus anticoagulant and thrombosis in systemic lupus erythematosus. Lancet. 1984 Mar 10;1(8376):574–575. doi: 10.1016/s0140-6736(84)90982-6. [DOI] [PubMed] [Google Scholar]
  30. Lazarchick J., Kizer J. The laboratory diagnosis of lupus anticoagulants. Arch Pathol Lab Med. 1989 Feb;113(2):177–180. [PubMed] [Google Scholar]
  31. Lesperance B., David M., Rauch J., Infante-Rivard C., Rivard G. E. Relative sensitivity of different tests in the detection of low titer lupus anticoagulants. Thromb Haemost. 1988 Oct 31;60(2):217–219. [PubMed] [Google Scholar]
  32. Lo S. C., Oldmeadow M. J., Howard M. A., Firkin B. G. Comparison of laboratory tests used for identification of the lupus anticoagulant. Am J Hematol. 1989 Apr;30(4):213–220. doi: 10.1002/ajh.2830300405. [DOI] [PubMed] [Google Scholar]
  33. Lockshin M. D., Druzin M. L., Goei S., Qamar T., Magid M. S., 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 Jul 18;313(3):152–156. doi: 10.1056/NEJM198507183130304. [DOI] [PubMed] [Google Scholar]
  34. Loizou S., McCrea J. D., Rudge A. C., Reynolds R., Boyle C. C., Harris E. N. Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp Immunol. 1985 Dec;62(3):738–745. [PMC free article] [PubMed] [Google Scholar]
  35. Love P. E., Santoro S. A. 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 May 1;112(9):682–698. doi: 10.7326/0003-4819-112-9-682. [DOI] [PubMed] [Google Scholar]
  36. Lubbe W. F., Butler W. S., Palmer S. J., Liggins G. C. Fetal survival after prednisone suppression of maternal lupus-anticoagulant. Lancet. 1983 Jun 18;1(8338):1361–1363. doi: 10.1016/s0140-6736(83)92141-4. [DOI] [PubMed] [Google Scholar]
  37. MARGOLIS J. The kaolin clotting time; a rapid one-stage method for diagnosis of coagulation defects. J Clin Pathol. 1958 Sep;11(5):406–409. doi: 10.1136/jcp.11.5.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mackworth-Young C. G., Loizou S., Walport M. J. Antiphospholipid antibodies and disease. Q J Med. 1989 Sep;72(269):767–777. [PubMed] [Google Scholar]
  39. Mannucci P. M., Canciani M. T., Mari D., Meucci P. The varied sensitivity of partial thromboplastin and prothrombin time reagents in the demonstration of the lupus-like anticoagulant. Scand J Haematol. 1979 May;22(5):423–432. doi: 10.1111/j.1600-0609.1979.tb00440.x. [DOI] [PubMed] [Google Scholar]
  40. Peck B., Hoffman G. S., Franck W. A. Thrombophlebitis in systemic lupus erythematosus. JAMA. 1978 Oct 13;240(16):1728–1730. [PubMed] [Google Scholar]
  41. Pengo V., Thiagarajan P., Shapiro S. S., Heine M. J. Immunological specificity and mechanism of action of IgG lupus anticoagulants. Blood. 1987 Jul;70(1):69–76. [PubMed] [Google Scholar]
  42. 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 Apr;106(4):524–531. doi: 10.7326/0003-4819-106-4-524. [DOI] [PubMed] [Google Scholar]
  43. Prentice R. L., Gatenby P. A., Loblay R. H., Shearman R. P., Kronenberg H., Basten A. Lupus anticoagulant in pregnancy. Lancet. 1984 Aug 25;2(8400):464–464. doi: 10.1016/s0140-6736(84)92938-6. [DOI] [PubMed] [Google Scholar]
  44. Ramsey-Goldman R. Pregnancy in systemic lupus erythematosus. Rheum Dis Clin North Am. 1988 Apr;14(1):169–185. [PubMed] [Google Scholar]
  45. Regan M. G., Lackner H., Karpatkin S. Platelet function and coagulation profile in lupus erythematosus. Studies in 50 patients. Ann Intern Med. 1974 Oct;81(4):462–468. doi: 10.7326/0003-4819-81-4-462. [DOI] [PubMed] [Google Scholar]
  46. Schleider M. A., Nachman R. L., Jaffe E. A., Coleman M. A clinical study of the lupus anticoagulant. Blood. 1976 Oct;48(4):499–509. [PubMed] [Google Scholar]
  47. Staub H. L., Harris E. N., Khamashta M. A., Savidge G., Chahade W. H., Hughes G. R. Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis. Ann Rheum Dis. 1989 Feb;48(2):166–169. doi: 10.1136/ard.48.2.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stevenson K. J., Easton A. C., Curry A., Thomson J. M., Poller L. The reliability of activated partial thromboplastin time methods and the relationship to lipid composition and ultrastructure. Thromb Haemost. 1986 Apr 30;55(2):250–258. [PubMed] [Google Scholar]
  49. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  50. Thiagarajan P., Pengo V., Shapiro S. S. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood. 1986 Oct;68(4):869–874. [PubMed] [Google Scholar]
  51. Thiagarajan P., Shapiro S. S., De Marco L. Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant. J Clin Invest. 1980 Sep;66(3):397–405. doi: 10.1172/JCI109869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Triplett D. A. Antiphospholipid antibodies and recurrent pregnancy loss. Am J Reprod Immunol. 1989 Jun;20(2):52–67. doi: 10.1111/j.1600-0897.1989.tb00639.x. [DOI] [PubMed] [Google Scholar]
  53. Triplett D. A., Brandt J. T. Lupus anticoagulants: misnomer, paradox, riddle, epiphenomenon. Hematol Pathol. 1988;2(3):121–143. [PubMed] [Google Scholar]
  54. Triplett D. A., Brandt J. T., Maas R. L. The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med. 1985 Oct;109(10):946–951. [PubMed] [Google Scholar]
  55. Triplett D. A., Brandt J. T., Musgrave K. A., Orr C. A. The relationship between lupus anticoagulants and antibodies to phospholipid. JAMA. 1988 Jan 22;259(4):550–554. [PubMed] [Google Scholar]
  56. Triplett D. A., Brandt J. Laboratory identification of the lupus anticoagulant. Br J Haematol. 1989 Oct;73(2):139–142. doi: 10.1111/j.1365-2141.1989.tb00242.x. [DOI] [PubMed] [Google Scholar]
  57. Valesini G., Tincani A., Harris E. N., Mantelli P. G., Allegri F., Palmieri G., Hughes G. R., Balsano F., Balestrieri G. Use of monoclonal antibodies to identify shared idiotypes on anticardiolipin and anti-DNA antibodies in human sera. Clin Exp Immunol. 1987 Oct;70(1):18–25. [PMC free article] [PubMed] [Google Scholar]
  58. Violi F., Ferro D., Quintarelli C., Alessandri C., Saliola M., Valesini G., Balsano F. Dilute aPTT prolongation by antiphospholipid antibodies in patients with liver cirrhosis. Thromb Haemost. 1990 Apr 12;63(2):183–186. [PubMed] [Google Scholar]
  59. Violi F., Ferro D., Saliola M., Quintarelli C., Alessandri C. Evaluation of D-dimer in patients with liver cirrhosis. Thromb Haemost. 1989 Dec 29;62(4):1149–1150. [PubMed] [Google Scholar]
  60. Violi F., Ferro D., Valesini G., Quintarelli C., Balsano F. Lupus anticoagulant in liver cirrhosis. Thromb Haemost. 1988 Apr 8;59(2):335–335. [PubMed] [Google Scholar]
  61. Violi F., Ferro D., Valesini G., Quintarelli C., Saliola M., Grandilli M. A., Balsano F. Tissue plasminogen activator inhibitor in patients with systemic lupus erythematosus and thrombosis. BMJ. 1990 Apr 28;300(6732):1099–1102. doi: 10.1136/bmj.300.6732.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Violi F., Valesini G., Ferro D., Tincani A., Balestrieri G., Balsano F. Anticoagulant activity of anticardiolipin antibodies. Thromb Res. 1986 Nov 15;44(4):543–547. doi: 10.1016/0049-3848(86)90332-4. [DOI] [PubMed] [Google Scholar]

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