Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism

Summary

The role of antiprothrombin (aPT) antibodies in the development of venous thromboembolism (VTE) is still uncertain. The aim of this study was to evaluate the potential role of aPT antibodies in the development of recurrent thromboembolism. Out of 236 consecutive symptomatic patients with an episode of acute VTE, antiphospholipid antibodies were found in 85 (36.0%), of whom 24 were carriers of aPT antibodies (10.2% of the entire cohort). A history of previous thromboembolism was identified in 56 patients (23.7%). The prevalence of previous thromboembolism was significantly higher in carriers than in non-carriers of antiphospholipid antibodies (OR=2.4; 95% CI, 1.3 to 4.4). Of the 24 patients with aPT antibodies, 12 had a history of previous thromboembolism. In a multivariate logistic regression analysis, in which the other categories of antiphospholipid antibodies were taken into account, as well as the patient’s age, sex, and the modality of clinical presentation, it was found that the presence of aPT antibodies was significantly associated with the prevalence of prior thromboembolism (OR=3.3; 95% CI, 1.3 to 8.6). Since aPT antibodies are more commonly identifiable in patients with multiple thrombotic episodes, they are a likely risk factor for recurrent thromboembolism.

Keywords

Anti-phospholipid antibodies - anti-prothrombin antibodies - venous thromboembolism

• References

• 1 Triplett DA. Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. Thromb Res 1995; 78: 1-31.
• 2 McNeil HP, Simpson RJ, Chesterman CN. et al. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: B2-glicoprotein I (apolipoprotein H). Proct Natl Acad Sci 1990; 87: 4120-4.
• 3 Galli M, Confurius P, Maassen C. et al. Anticardiolipin antibodies (ACA) direct not to cardiolipin but to plasma protein cofactor. Lancet 1990; 335: 1544-7.
• 4 Arvieux J, Darnige L, Reber G. et al. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulant. Thromb Haemost 1995; 74: 1120-5.
• 5 Loeliger A. Prothrombin as co-factor of the circulating anticoagulant in systemic lupus erythematosus?. Thromb Diath Haemorrh 1959; 03: 237-56.
• 6 Guerin J, Smith W, White B. et al. Antibodies to prothrombin in antiphospholipid syndrome and inflammatory disorder. Br J Haematol 1998; 102: 896-902.
• 7 Simioni P, Prandoni P, Zanon E. et al. Deep vein thrombosis and lupus anticoagulant: a case control study. Thromb Haemost 1996; 76: 187-9.
• 8 Ginsberg JS, Wells PS, Brill-Edwards P. et al. Antiphospholipid antibodies and venous thromboembolism. Blood 1995; 86: 3685-91.
• 9 Prandoni P, Simioni P, Girolami A. Antiphospholipid antibodies, recurrent thromboembolism and intensity of oral anticoagulation. Thromb Haemost 1996; 75: 859.
• 10 Levine SR, Salowich-Palm L, Sawaya K. et al. IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent trombo-occlusive events and death. Stroke 1997; 28: 1660-5.
• 11 Ginsburg KS, Liang MH, Newcomer L. etal Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992; 117: 997-1002.
• 12 Schulman S, Svenungsson E, Granqvist S. and the Duration of Anticoagulation Study Group Anticardiolipin Antibodies predict early recurrence thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med. 1998; 104: 332-8.
• 13 Wahl DG, De Maistre E, Guillemin F. et al. Antibodies against phospholipids and β-2 glycoprotein I increase the risk of recurrent venous thromboembolism in patient without systemic lupus erythematosus Q J Med. 1998; 91: 125-30.
• 14 Zanon E, Prandoni P, Vianello F. et al. Anti-β2-Glycoprotein I antibodies in patients with acute thromboembolism: prevalence and association with recurrent thromboembolism. Thromb Res 1999; 96: 269-74.
• 15 Previtali S, Barbui T, Galli M. Anti-beta2-glycoprotein I and anti-prothrombin antibodies in antiphospholipid-negative patients with thrombosis: a case control study. Thromb Haemost 2002; 88: 729-32.
• 16 Nojima J, Kuratsune H, Suehisa E. et al. Antiprothrombin 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.
• 17 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.
• 18 Pasquier E, Amiral J, de Saint LMartin. et al. A cross sectional study of antiphospholipidprotein antibodies in patients with venous thromboembolism. Thromb Haemost 2001; 86: 538-42.
• 19 Donohoe S, Mackie IJ, Isenberg D. et al. Antiprothrombin antibodies: assay conditions and clinical associations in the anti-phospholipid syndrome. Br J Haematol 2001; 113: 544-9.
• 20 Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood 1999; 93: 2149-57.
• 21 Cogo A, Lensing AWA, Wells PS. et al. Noninvasive diagnostic tests for the diagnosis of clinically suspected deep-vein thrombosis. Haemostasis 1995; 25: 27-39.
• 22 Koopman MMW, Büller HR, ten Cate JW. Diagnosis of recurrent deep vein thrombosis. Haemostasis 1995; 25: 49-57.
• 23 Kearin C, Hirsh J. The diagnosis of pulmonary embolism. Haemostasis 1995; 25: 72-87.
• 24 Brandt JT, Triplett DA, Alving B. et al. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995; 74: 1185-90.
• 25 Horbach DA, Oort E, Donders R. 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.