A Cross Sectional Study of Antiphospholipid-protein Antibodies in Patients with Venous Thromboembolism

Summary

Objective: To look for an association between venous thromboembolism (VTE) and antiphospholipid antibodies (aPL) in patients without Systemic Lupus Erythematosus (SLE) when implementing, beside conventional assays, new tests for aPL screening directed towards purified proteic targets. Methods: We conducted a cross-sectional, hospital-based study of consecutive unselected outpatients. We compared VTE+ patients to VTE- among 398 consecutive unselected outpatients referred for clinical suspicion of VTE. To detect aPL, the following ELISAs were performed : 1) a conventional standardized ELISA 2) an improved APA assay, 3) an anti-Beta2GPI ELISA, 4) an anti-Annexin V ELISA, 5) an anti-Prothrombin ELISA. We sought an association between VTE and aPL through a quantitative (t-test) and a qualitative comparison (chi-square test, according to the cut-off values set as the 95th percentile of aPL distribution). First we conducted an analysis of all patients. Then we stratified them into 2 subgroups, with or without a wellknown risk factor for VTE (prolonged immobilization >72h, surgery or trauma within the past three months, current malignancy). Results: 61% of patients were classified as VTE-positive. Before stratification, we did not find any significant association between the VTE status and aPL. However, after stratification, in the subgroup without risk factors for VTE, the frequency of positive values as regards the anti Prothrombin antibodies detection was significantly higher in VTE+ patients (p = 0,04). Conclusion: The presence of anti Prothrombin antibodies might be an independent risk factor of VTE. However systematic screening for aPL in non SLE patients referred for VTE suspicion at the time of the thromboembolic event has little clinical relevance.

Keywords

Venous thrombo-embolism - anticardiolipin antibodies - anti annexin V antibodies - anti prothrombin antibodies - anti Beta2GPI antibodies

• References

• 1 Petri M. Diagnosis of Antiphospholipid Antibodies. Rhumatic Disease Clinics of NorthAmerica 1994; 20: 443-69.
• 2 Roubey R. Antigenic specificities of antiphospholipid autoantibodies: implications for clinical laboratory testing and diagnosis of the antiphospholipid syndrome. Lupus 1995; 5: 425-30.
• 3 Galli M. Non Beta2-glycoprotein I cofactors for antiphospholipid antibodies. Lupus 1996; 5: 388-92.
• 4 Piette JC. 1996 diagnostic and classification criteria for the antiphospholipid/cofactors syndrome: a “mission impossible”?. Lupus 1996; 5: 354-63.
• 5 Roubey R. Immunology of the antiphospholipid syndrome. Arthritis Rheum 1996; 39: 1444-54.
• 6 Triplett DA. Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. Thromb Res 1995; 78: 1-31.
• 7 Carreras LO, Forastiero RR. Pathogenic role of antiprotein-phospholipid antibodies. Haemostasis 1996; 26 (Suppl. 04) 340-57.
• 8 Alarcon-Segovia D, Deleze M, Oria CV, Sanchez-Guerrero J, Gomez-Pacheco L, Cabiedes J, Fernandez L, Ponce de Leon S. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erytthematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore) 1989; 68: 353-65.
• 9 Long AA, Ginsberg JS, Brill-Edwards P, Johnston M, Turner C, Denburg JA. et al. The relation of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectionnal study. Thromb Haemost 1991; 66: 520-4.
• 10 Boey ML, Colaco CB, Ghanavi AE, Elkon KB, Loizou S, Hugues GR. Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. Br Med J 1983; 287: 1021-3.
• 11 Gomez-Pacheco L, Villa AR, Drenkard C, Cabiedes J, Cabral AR, Alarcon-Segovia D. Serum Anti-Beta2-glycoprotein-I and Anticardiolipin Antibodies during Thrombosis in Systemic Lupus Erythematosus Patients. Am J Med 1999; 106: 417-23.
• 12 Wahl DG, Guillemin F, de Maistre E, Perret C, Lecompte T, Thibaut G. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus. A meta-analysis. Lupus 1997; 6: 467-73.
• 13 Wahl DG, Guillemin F, de Maistre E, Perret-Guillaume C, Lecompte T, Thibaut G. Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus 1998; 7: 15-22.
• 14 Simioni P, Prandoni P, Zanon E, Saracino MA, Scudeller A, Villalta S, Scarano L, Girolami B, Benedetti L, Girolami A. Deep Venous Thrombosis and Lupus Anticoagulant. A Case-control Study. Thromb Haemost 1996; 76: 187-9.
• 15 Ginsberg JS, Wells PS, Brill-Edwards P, Donovan D, Moffatt K, Johnston M, Srevens P, Hirsh J. Antiphospholipid Antibodies and Venous Thromboembolism. Blood 1995; 86: 3685-91.
• 16 Palosuo T, Virtamo J, Haukka J, Taylor PR, Aho K, Puurunen M, Vaarala O. 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.
• 17 Oger E, Leroyer C, Dueymes M, Le Moigne E, Bressollette L, Escoffre M, Youinou P, Mottier D. Association between IgM anticardiolipin antibodies and deep venous thrombosis in patients without systemic lupus erythematosus. Lupus 1997; 6: 455-61.
• 18 Ginsburg KS, Liang MH, Newcomer L, Goldhaber SZ, Schur PH, Hennekens CH, Stampfer MJ. Anticardiolipin Antibodies and the Risk For Ischemic Stroke and Venous Thrombosis. Annals of Internal Medicine 1992; 117: 997-1002.
• 19 Bongard O, Reber G, Bounameaux H, de Moerloose P. Anticardiolipin Antibodies in Acute Venous Thromboembolism. Thromb Haemost 1992; 67: 724.
• 20 Leroyer C, Mercier B, Escoffre M, Férec C, Mottier D. Factor V Leiden prevalence in venous thromboembolism patients. Chest 1997; 111: 1603-6.
• 21 The Pioped investigators.. Value of the ventilation/perfusion scan in acute pulmonary. Jama 1990; 263: 2753-9.
• 22 Amiral J, Minard F, Chambrette B. Development of standardized immunoassays for indentification, characterization and quantitation of antiphospholipid antibodies (APA). Biol Clin Hematol 1991; 13: 81-8.
• 23 Amiral J, Adam M, Cluzeau D, Vissac AM, Grimaux M, et Maillet T. Anti-corps phospholipides dépendants: données actuelles et développement de trousses de dosages optimisés. Revue française des laboratoires 1997; 297: 25-33.
• 24 Amiral J. Diagnosis Approach of Phospholipid-Dependent Antibodies. Haemostasis 1999; 29: 135-49.
• 25 Gris JC, Quéré I, Sanmarco M, Boutière B, Mercier M, Amiral J, Hubert AM, Ripart-Neveu S, Hoffet M, Tailland ML, Rousseau O, Montpeyroux F, Dauzat M, Sampol J, Daures JP, Berlan J, Marès P. Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nîmes obstetricians and haematologists study – NOHA. Thromb Haemost 2000; 84: 228-36.
• 26 Satoh A, Suzuki K, Takayama E, Kojima K, Hidaka T, Kawakami M, Matsumoto I, Ohsuzu F. Detection of anti-annexin IV and V antibodies in patient with antiphospholipid syndrome and systemic lupus erythematosus. J Rheumatol 1999; 26: 1715-20.
• 27 Schulman S, Svenungsson E, Granqvist S. and the Duration of Anticoagulation Study Group.. Anticardiolipin Antibodies Predict Early Recurrence of Thromboembolism and Death among Patients with Venous Thromboembolism following Anticoagulant Therapy. Am J Med 1998; 104: 332-8.
• 28 Zanon E, Prandoni P, Vianello F, Saggiorato G, Carroro G, Bagatella P, Girolami A. Anti-beta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism. Thromb Res 1999; 96: 269-74.