Antiprothrombin antibodies detected in two different assay systems

Maria Laura Bertolaccini; Tatsuya Atsumi; Takao Koike; Graham R. V. Hughes; Munther A. Khamashta

doi:10.1160/TH04-06-0382

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 93(02): 289-297
DOI: 10.1160/TH04-06-0382

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Antiprothrombin antibodies detected in two different assay systems

Prevalence and clinical significance in systemic lupus erythematosus

Maria Laura Bertolaccini

¹Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK

,

Tatsuya Atsumi

²Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan

,

Takao Koike

²Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan

,

Graham R. V. Hughes

¹Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK

,

Munther A. Khamashta

¹Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK

› Institutsangaben

Abstract

Summary

We evaluated the clinical significance of aPT and aPS-PT by testing for the presence of these antibodies in 212 SLE patients and in 100 healthy individuals. Results show that anti-prothrombin antibodies were found in 47% of the patients (aPT in 31% and aPS-PT in 31%). Their presence did not correlate with that of aCL, anti-β 2GPI, LA and/or anti-protein S. IgG but not IgM aPT were more frequently found in patients with thrombosis than in those without. IgG and IgM aPS-PT were also more frequent in patients with thrombosis (venous and/or arterial) than in those without. Levels of IgG aPT and IgG and IgM aPS-PT were higher in patients with thrombosis than in those without. Although aPT and aPS-PT were more frequently found in women with adverse obstetric history than in those without, the differences were not statistically significant. More significantly, 48% of the patients with aPL-related clinical features who were negative for standard tests had antiprothrombin antibodies. We can conclude that aPT and aPS-PT are frequently found in SLE. Their presence is associated with thrombosis, making these antibodies potential markers for the APS. Testing for these antibodies could be of clinical benefit in patients who are negative for the routinely used tests.

Keywords

Antiphospholipid syndrome - pregnancy morbidity - coagulation - thrombosis - lupus anticoagulant

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Referenzen

References
1 Hughes GRV. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant.. Br Med J 1983; 287: 1088-89.
2 Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome.. Blood 1999; 93: 2149-57.
3 Arvieux J, Darnige L, Caron C. et al Development of an ELISA for autoantibodies to prothrombin show- ing their prevalence in patients with lupus anticoagulants.. Thromb Haemost 1995; 74: 1120-25.
4 Galli M, Beretta G, Daldossi M. et al Different anticoagulant and immunological properties of antiprothrombin antibodies in patients with antiphospholipid antibodies.. Thromb Haemost 1997; 77: 486-91.
5 Atsumi T, Ieko M, Bertolaccini ML. et al Association of autoantibodies against the phosphatidylserineprothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant.. Arthritis Rheum 2000; 43: 1982-93.
6 Petri M, Miller J, Goldman D, Ebert R. Anti-plasma protein antibodies are predictive of thrombotic events.. Arthritis Rheum 1994; 37: S281 (abstract)
7 Puurunen M, Vaarala O, Julkunen H. et al Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus.. Clin Immunol Immunopathol 1996; 80: 16-22.
8 Bertolaccini ML, Atsumi T, Khamashta MA. et al Autoantibodies to human prothrombin and clinical manifestations in 207 patients with systemic lupus erythematosus.. J Rheumatol 1998; 25: 1104-08.
9 Tan EM, Cohen AS, Fries JF. et al The 1982 revised criteria for the classification of systemic lupus erythematosus.. Arthritis Rheum 1982; 25: 1271-77.
10 Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.. Arthritis Rheum 1997; 40: 1725
11 Wilson WA, Gharavi AE, Koike T. et al International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.. Arthritis Rheum 1999; 42: 1309-11.
12 Harris EN, Gharavi AE, Patel SP. et al Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986.. Clin Exp Immunol 1987; 68: 215-22.
13 Amengual O, Atsumi T, Khamashta MA. et al Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome.. Br J Rheumatol 1996; 35: 1239-43.
14 Bertolaccini ML, Sanna G, Ralhan S. et al Antibodies directed to protein S in patients with systemic lupus erythematosus: prevalence and clinical significance.. Thromb Haemost 2003; 90: 636-41.
15 Brandt JT, Triplett DA, Alving B. et al Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.. Thromb Haemost 1995; 74: 1185-90.
16 Thiagarajan P, Pengo V, Shapiro S. The use of dilute Russell viper venom time for the diagnosis of lupus anticoagulants.. Blood 1986; 68: 869-74.
17 Pengo V, Biasolo A, Brocco T. et al Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid reactive antibodies.. Thromb Haemost 1996; 75: 721-24.
18 Galli M. Non beta 2-glycoprotein I cofactors for antiphospholipid antibodies.. Lupus 1996; 5: 388-92.
19 Horbach DA, van Oort E, Donders RC. et al Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies.. Thromb Haemost 1996; 76: 916-24.
20 Munoz-Rodriguez FJ, Reverter JC, Font J. et al Prevalence and clinical significance of antiprothrombin antibodies in patients with systemic lupus erythematosus or with primary antiphospholipid syndrome.. Haematologica 2000; 85: 632-37.
21 Galli M, Luciani D, Bertolini G. et al Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome.. Blood 2003; 102: 2717-23.
22 Horbach DA, van Oort E, Derksen RH. et al The contribution of anti-prothrombin-antibodies to lupus anticoagulant activity--discrimination between functional and non-functional anti-prothrombin-antibodies.. Thromb Haemost 1998; 79: 790-95.
23 Vaarala O, Puurunen M, Manttari M. et al Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.. Thromb Haemost 1996; 75: 456-59.
24 Palosuo T, Virtamo J, Haukka J. et al High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men--a nested case-control study.. Thromb Haemost 1997; 78: 1178-82.
25 Forastiero RR, Martinuzzo ME, Cerrato GS. et al Relationship of anti beta2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies.. Thromb Haemost 1997; 78: 1008-14.
26 Forastiero R, Martinuzzo M, Adamczuk Y. et al Occurrence of anti-prothrombin and anti-beta2-glycoprotein I antibodies in patients with history of thrombosis.. J Lab Clin Med 1999; 134: 610-15.
27 Zanon E, Saggiorato G, Ramon R. et al Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism.. Thromb Haemost 2004; 91: 255-8.
28 Amengual O, Atsumi T, Khamashta MA. et al Clinical significance of anti-beta 2-glycoprotein I antibodies.. Ann Med Interne (Paris) 1996; 147: 15-7.
29 Inanc M, Donohoe S, Ravirajan CT. et al Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome.. Br J Rheumatol 1998; 37: 1089-94.
30 Funke A, Bertolaccini ML, Atsumi T. et al Autoantibodies to prothrombin-phosphatidylserine complex: clinical significance in systemic lupus erythematosus.. Arthritis Rheum 1998; 41: S240 (abstract)
31 Bevers EM, Galli M, Barbui T. et al Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin.. Thromb Haemost 1991; 66: 629-32.
32 Nojima J, Kuratsune H, Suehisa E. et al Anti-prothrombin antibodies combined with lupus anti-coagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus.. Br J Haematol 2001; 114: 647-54.