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January 22, 1988, Vol 259, No. 4 >
ARTICLE | January 22, 1988

The Relationship Between Lupus Anticoagulants and Antibodies to Phospholipid FREE

Douglas A. Triplett, MD; John T. Brandt, MD; Kim A. Musgrave, MT; Carol A. Orr, MT
[+] Author Affiliations

Reprint requests to Ball Memorial Hospital Inc, Department of Pathology, 2401 University Ave, Muncie, IN 47303-3499 (Dr Triplett).


JAMA. 1988;259(4):550-554. doi:10.1001/jama.1988.03720040042024
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References

The relationship between lupus anticoagulants and antibodies directed against negatively charged phospholipids, as measured by an enzyme-linked immunosorbent assay, was explored in a series of plasma samples from 100 patients with well-characterized lupus anticoagulants. Only 73% of the patients had detectable IgG, IgM antibodies, or both, to one or more of four phospholipids. Of these patients, 29% had IgG-type antibodies only, 56% had both IgG and IgM antibodies, and 15% had IgM antibodies only. Of the 100 patients, 19% had a history of thrombosis, 8% had a history of spontaneous abortion, and 6% had a history of seizure disorder. These complications occurred in the presence (80%) and absence (20%) of detectable antiphospholipid antibodies. Drug-related antibodies were observed in 34 patients; of these, 71% had detectable antiphospholipid antibodies and 24% had a history of thrombosis. There were ten patients with lupus anticoagulants associated with infections; none of these patients had a history of thrombosis. The results indicate that antiphospholipid antibodies are not present in all patients with lupus anticoagulants, that the presence of antiphospholipid antibodies in patients with lupus anticoagulants does not increase the risk of thrombosis in these patients, and that drug-related antibodies are associated with an increased risk of thrombosis. Lupus anticoagulants and antiphospholipid antibodies seem to define two distinct but related patient populations, each associated with an increased risk of thrombosis.

(JAMA 1988;259:550-554)

REFERENCES

1 +
Shapiro SS,  Thiagarajan P: Lupus anticoagulants , in Spaet TH (ed): Progress in Hemostasis and Thrombosis . New York, Grune & Stratton, 1982;, vol 6, pp 263-285.
2 +
Espinoza LR, Hartmann RC:  Significance of the lupus anticoagulant. Am J Hematol 1986;;22:331-337.
3 +
Mueh JR, Herbst KD, Rapaport SI:  Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980;;92:156-159.
4 +
Elias M, Eldor A:  Thromboembolism in patients with the 'lupus'-type circulating anticoagulant. Arch Intern Med 1984;;144:510-515.
5 +
Fisher M, McGehee W:  Cerebral infarct, TIA, and lupus inhibitor. Neurology 1986;;36:1234-1237.
6 +
Carreras LO, DeFreyn G, Machin SJ, et al:  Arterial thrombosis, intrauterine death and 'lupus' anticoagulant: Detection of immunoglobulin interfering with prostacyclin production. Lancet 1981;;1: 244-246.
7 +
Conley CL, Hartmann RC:  A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952;;31:621-622.
8 +
Laurell AB, Nilsson IM:  Hypergammaglobulinemia, circulating anticoagulant and biologically false positive Wasserman reaction. J Lab Clin Med 1957;;49:694-707.
9 +
Thiagarajan P, Shapiro SS, DeMarco L:  Monoclonal immunoglobulin Mλ coagulation inhibitor with phospholipid specificity: Mechanism of a lupus anticoagulant. J Clin Invest 1980;;66:397-405.
10 +
Rauch J, Tannenbaum M, Tannenbaum H, et al:  Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems. J Biol Chem 1986;;261:9672-9677.
11 +
Harris EN, Gharavi AE, Boey ML, et al:  Anticardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983;;2: 1211-1214.
12 +
Lockshin MD, Druzin ML, Goei S:  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.
13 +
Hughes GRV, Harris EN, Gharavi AE:  The anticardiolipin syndrome. J Rheumatol 1986;;13: 486-489.
14 +
Harris EN, Chan JKH, Asherson RA, et al:  Thrombosis, recurrent fetal loss, and thrombocytopenia: Predictive value of the anticardiolipin antibody assay. Arch Intern Med 1986;;146: 2153-2156.
15 +
Gharavi AE, Harris EN, Asherson RA, et al:  Anticardiolipin (anti CL) isotypes: A study of their clinical relevance. Clin Rheumatol 1986;;5:154-155.
16 +
Gharavi AE, Harris EN, Asherson RA, et al:  Anticardiolpin antibodies: Isotype distribution and phospholipid specificity. Ann Rheum Dis 1987;;46: 1-6.
17 +
Harris EN, Loizou S, Englert H, et al:  Anticardiolipin antibodies and lupus anticoagulant. Lancet 1984;;2:1099.
18 +
Harris EN, Gharavi AE, Tincani A, et al:  Affinity purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol 1985;;17:155-162.
19 +
Violi F, Valesini G, Ferro D, et al:  Anticoagulant activity of anticardiolipin antibodies. Thromb Res 1986;;44:543-547.
20 +
Triplett DA, Brandt JT, Kaczor D, et al:  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.
21 +
Schleider MA, Nachman RL, Jaffe EA, et al:  A clinical study of the lupus anticoagulant. Blood 1976;;48:499-509.
22 +
Triplett DA, Harms CS: Procedures for the Coagulation Laboratory . Chicago, American Society of Clinical Pathologists Press, 1981;.
23 +
Triplett DA, Brandt JT, Maas RL:  The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med 1985;;109:946-951.
24 +
Loizou S, McCrea JD, Rudge AC, et al:  Measurement of anticardiolipin antibodies by an enzyme linked immunosorbent assay (ELISA): Standardization and quantitation of results. Clin Exp Immunol 1985;;62:738-745.
25 +
Harris EN, Hughes GRV:  Standardizing the anti-cardiolipin antibody test. Lancet 1987;;1:277.
26 +
Gastineau DA, Kazmier FJ, Nichols WL, et al:  Lupus anticoagulant: An analysis of the clinical and laboratory features of 219 cases. Am J Hematol 1985;;19:265-275.
27 +
Lechner K, Pabinger-Fasching I:  Lupus anticoagulants and thrombosis: A study of 25 cases and review of the literature. Haemostasis 1985;;15: 254-262.
28 +
Unander AM, Norberg R, Hahn L, et al:  Anticardiolipin antibodies and complement in 99 women with habitual abortion. Am J Obstet Gynecol 1987;; 156:114-119.
29 +
Canoso RT, Sise HS:  Chlorpromazine induced lupus anticoagulant and associated immunologic abnormalities. Am J Hematol 1982;;13:121-129.
30 +
Freyssinet J-M, Wiesel M-L, Gauchy J, et al:  An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified thrombomodulin activity: A mechanism for thrombosis. Thromb Haemost 1986;;55:309-313.
31 +
Canoso RT, Oliveria RM:  Lack of thrombotic diathesis in patients with chlorpromazine induced lupus anticoagulants and antiphospholipid antibodies, abstracted. Blood 1985;;66( (suppl 1) ):348.
32 +
Zarrabi MH, Zucker S, Miller F, et al:  Immunologic and coagulation disorders in chlorpromazine treated patients. Ann Intern Med 1979;;91: 194-199.
33 +
Davis S, Furie BC, Griffin JH, et al:  Circulating inhibitors of blood coagulation associated with procainamide-induced lupus erythematosus. Am J Hematol 1978;;4:402-410.
34 +
Hamsten A, Norberg R, Bjorkholm M, et al:  Antibodies to cardiolipin in young survivors of myocardial infarction: An association with recurrent cardiovascular events. Lancet 1986;;1:113-115.
35 +
Morton K, Gavaghan TP, Krilis SA, et al:  Coronary artery bypass graft failure: An autoimmune phenomenon? Lancet 1986;;1:1353-1357.
36 +
Vaarala 0, Palosuo T, Kleemola M, et al:  Anticardiolipin response in acute infections. Clin Immunol Immunopathol 1986;;41:8-15.
37 +
Canoso RT, Zon LI, Groopman JE:  Anticardiolipin antibodies associated with HTLV-III infection. Br J Haematol 1987;;65:495-498.
38 +
Bloom EJ, Abrams DI, Rodgers G:  Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986;;256:491-493.
39 +
Gold JE, Haubenstock A, Zalusky R:  Lupus anticoagulant and AIDS. Lancet 1986;;1:1252-1253.
40 +
Lockshin MD, Qamar T, Druzin ML, et al:  Antibody to cardiolipin, lupus anticoagulant, and fetal death. J Rheumatol 1987;;14:259-262.
41 +
Colaco CB, Male DK:  Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: Distinct profiles of epitope specificity. Clin Exp Immunol 1985;;59:449-456.
42 +
Shoenfeld Y, Rauch J, Massicote H, et al:  Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med 1983;;308:414-420.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Shapiro SS,  Thiagarajan P: Lupus anticoagulants , in Spaet TH (ed): Progress in Hemostasis and Thrombosis . New York, Grune & Stratton, 1982;, vol 6, pp 263-285.
2 +
Espinoza LR, Hartmann RC:  Significance of the lupus anticoagulant. Am J Hematol 1986;;22:331-337.
3 +
Mueh JR, Herbst KD, Rapaport SI:  Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980;;92:156-159.
4 +
Elias M, Eldor A:  Thromboembolism in patients with the 'lupus'-type circulating anticoagulant. Arch Intern Med 1984;;144:510-515.
5 +
Fisher M, McGehee W:  Cerebral infarct, TIA, and lupus inhibitor. Neurology 1986;;36:1234-1237.
6 +
Carreras LO, DeFreyn G, Machin SJ, et al:  Arterial thrombosis, intrauterine death and 'lupus' anticoagulant: Detection of immunoglobulin interfering with prostacyclin production. Lancet 1981;;1: 244-246.
7 +
Conley CL, Hartmann RC:  A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest 1952;;31:621-622.
8 +
Laurell AB, Nilsson IM:  Hypergammaglobulinemia, circulating anticoagulant and biologically false positive Wasserman reaction. J Lab Clin Med 1957;;49:694-707.
9 +
Thiagarajan P, Shapiro SS, DeMarco L:  Monoclonal immunoglobulin Mλ coagulation inhibitor with phospholipid specificity: Mechanism of a lupus anticoagulant. J Clin Invest 1980;;66:397-405.
10 +
Rauch J, Tannenbaum M, Tannenbaum H, et al:  Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems. J Biol Chem 1986;;261:9672-9677.
11 +
Harris EN, Gharavi AE, Boey ML, et al:  Anticardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983;;2: 1211-1214.
12 +
Lockshin MD, Druzin ML, Goei S:  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.
13 +
Hughes GRV, Harris EN, Gharavi AE:  The anticardiolipin syndrome. J Rheumatol 1986;;13: 486-489.
14 +
Harris EN, Chan JKH, Asherson RA, et al:  Thrombosis, recurrent fetal loss, and thrombocytopenia: Predictive value of the anticardiolipin antibody assay. Arch Intern Med 1986;;146: 2153-2156.
15 +
Gharavi AE, Harris EN, Asherson RA, et al:  Anticardiolipin (anti CL) isotypes: A study of their clinical relevance. Clin Rheumatol 1986;;5:154-155.
16 +
Gharavi AE, Harris EN, Asherson RA, et al:  Anticardiolpin antibodies: Isotype distribution and phospholipid specificity. Ann Rheum Dis 1987;;46: 1-6.
17 +
Harris EN, Loizou S, Englert H, et al:  Anticardiolipin antibodies and lupus anticoagulant. Lancet 1984;;2:1099.
18 +
Harris EN, Gharavi AE, Tincani A, et al:  Affinity purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol 1985;;17:155-162.
19 +
Violi F, Valesini G, Ferro D, et al:  Anticoagulant activity of anticardiolipin antibodies. Thromb Res 1986;;44:543-547.
20 +
Triplett DA, Brandt JT, Kaczor D, et al:  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.
21 +
Schleider MA, Nachman RL, Jaffe EA, et al:  A clinical study of the lupus anticoagulant. Blood 1976;;48:499-509.
22 +
Triplett DA, Harms CS: Procedures for the Coagulation Laboratory . Chicago, American Society of Clinical Pathologists Press, 1981;.
23 +
Triplett DA, Brandt JT, Maas RL:  The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med 1985;;109:946-951.
24 +
Loizou S, McCrea JD, Rudge AC, et al:  Measurement of anticardiolipin antibodies by an enzyme linked immunosorbent assay (ELISA): Standardization and quantitation of results. Clin Exp Immunol 1985;;62:738-745.
25 +
Harris EN, Hughes GRV:  Standardizing the anti-cardiolipin antibody test. Lancet 1987;;1:277.
26 +
Gastineau DA, Kazmier FJ, Nichols WL, et al:  Lupus anticoagulant: An analysis of the clinical and laboratory features of 219 cases. Am J Hematol 1985;;19:265-275.
27 +
Lechner K, Pabinger-Fasching I:  Lupus anticoagulants and thrombosis: A study of 25 cases and review of the literature. Haemostasis 1985;;15: 254-262.
28 +
Unander AM, Norberg R, Hahn L, et al:  Anticardiolipin antibodies and complement in 99 women with habitual abortion. Am J Obstet Gynecol 1987;; 156:114-119.
29 +
Canoso RT, Sise HS:  Chlorpromazine induced lupus anticoagulant and associated immunologic abnormalities. Am J Hematol 1982;;13:121-129.
30 +
Freyssinet J-M, Wiesel M-L, Gauchy J, et al:  An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified thrombomodulin activity: A mechanism for thrombosis. Thromb Haemost 1986;;55:309-313.
31 +
Canoso RT, Oliveria RM:  Lack of thrombotic diathesis in patients with chlorpromazine induced lupus anticoagulants and antiphospholipid antibodies, abstracted. Blood 1985;;66( (suppl 1) ):348.
32 +
Zarrabi MH, Zucker S, Miller F, et al:  Immunologic and coagulation disorders in chlorpromazine treated patients. Ann Intern Med 1979;;91: 194-199.
33 +
Davis S, Furie BC, Griffin JH, et al:  Circulating inhibitors of blood coagulation associated with procainamide-induced lupus erythematosus. Am J Hematol 1978;;4:402-410.
34 +
Hamsten A, Norberg R, Bjorkholm M, et al:  Antibodies to cardiolipin in young survivors of myocardial infarction: An association with recurrent cardiovascular events. Lancet 1986;;1:113-115.
35 +
Morton K, Gavaghan TP, Krilis SA, et al:  Coronary artery bypass graft failure: An autoimmune phenomenon? Lancet 1986;;1:1353-1357.
36 +
Vaarala 0, Palosuo T, Kleemola M, et al:  Anticardiolipin response in acute infections. Clin Immunol Immunopathol 1986;;41:8-15.
37 +
Canoso RT, Zon LI, Groopman JE:  Anticardiolipin antibodies associated with HTLV-III infection. Br J Haematol 1987;;65:495-498.
38 +
Bloom EJ, Abrams DI, Rodgers G:  Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986;;256:491-493.
39 +
Gold JE, Haubenstock A, Zalusky R:  Lupus anticoagulant and AIDS. Lancet 1986;;1:1252-1253.
40 +
Lockshin MD, Qamar T, Druzin ML, et al:  Antibody to cardiolipin, lupus anticoagulant, and fetal death. J Rheumatol 1987;;14:259-262.
41 +
Colaco CB, Male DK:  Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: Distinct profiles of epitope specificity. Clin Exp Immunol 1985;;59:449-456.
42 +
Shoenfeld Y, Rauch J, Massicote H, et al:  Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med 1983;;308:414-420.

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