Arterial and Venous Thrombosis as a Symptom of Antiphospholipid Syndrome – A Noticeable Analysis from the Past.
Main Article Content
Abstract
Antiphospholipid syndrome (APS), defined as combination of venous and/or arterial thrombosis as well as obstetric complications with antiphospholipid antibodies presence in blood, is an example of acquired thrombophilia. The thrombotic episodes in the APS course are highly recurrent, with an increasing incidence with years after secondary anticoagulant prophylaxis cessation.
In between 2005-2011 a study was conducted in Poznań, Poland, with the aim to find a correlation between actual APS diagnostic guidelines (criteria from Sydney’2006) and the clinical feature of thrombosis in this syndrome with coexistence of inherited thrombophilia and risk factors for cardio-vascular disease included. Additionally, a selection of the highest thromboembolic risk group was made among asymptomatic patients with antiphospholipid antibodies (APA) detected to compare with APS patients. An association between a type of laboratory test confirming the longtime APA presence and thrombotic risk was analyzed as well.
The follow up had lasted for meanly 47 months and included 75 patients (50 females and 25 males) at the mean age of 43, divided into three groups (25 persons each): I – with asymptomatic APA, IIA – with arterial episodes in the history and IIB – with past venous complications in the course of APS. The majority of them comprised persons with primary APS or with asymptomatic APA (aAPA) - without any other autoimmune diseases.
The laboratory tests included: lupus anticoagulant (LA) according to the 3-step procedure recommended by ISTH (International Society on Thrombosis and Hemostasis), anticardiolipin (ACA) – of IgG and IgM class and anti-β2-glycoprotein I (aβ 2 GPI) – of IgG class, both with the cut-off value of 99 percentile. D-dimer and fibrinogen concentration, protein C and antithrombin activity, activated protein C resistance, free protein S concentration, factor VIII were further analyzed.
Among comorbidities and risk factors for venous and arterial thrombosis, there was significantly more frequent incidence of autoimmune diseases in the asymptomatic group of people compared to patients after thromboembolic episodes.
Most often the aAPA presence was confirmed in the LA tests – the majority of positive results appeared among patients with asymptomatic course and with past venous thrombosis as well and less frequently - in the group of arterial episodes in the history.
Any significant differences were found in the reference to the incidence of thrombotic episodes in the retrospective assessment of symptomatic patients and prospective – in the whole investigated group, although the time of their occurrence after beginning of observation period almost doubled in people with past thromboembolic episodes, comparing to the earlier asymptomatic persons.
In between 2005-2011 a study was conducted in Poznań, Poland, with the aim to find a correlation between actual APS diagnostic guidelines (criteria from Sydney’2006) and the clinical feature of thrombosis in this syndrome with coexistence of inherited thrombophilia and risk factors for cardio-vascular disease included. Additionally, a selection of the highest thromboembolic risk group was made among asymptomatic patients with antiphospholipid antibodies (APA) detected to compare with APS patients. An association between a type of laboratory test confirming the longtime APA presence and thrombotic risk was analyzed as well.
The follow up had lasted for meanly 47 months and included 75 patients (50 females and 25 males) at the mean age of 43, divided into three groups (25 persons each): I – with asymptomatic APA, IIA – with arterial episodes in the history and IIB – with past venous complications in the course of APS. The majority of them comprised persons with primary APS or with asymptomatic APA (aAPA) - without any other autoimmune diseases.
The laboratory tests included: lupus anticoagulant (LA) according to the 3-step procedure recommended by ISTH (International Society on Thrombosis and Hemostasis), anticardiolipin (ACA) – of IgG and IgM class and anti-β2-glycoprotein I (aβ 2 GPI) – of IgG class, both with the cut-off value of 99 percentile. D-dimer and fibrinogen concentration, protein C and antithrombin activity, activated protein C resistance, free protein S concentration, factor VIII were further analyzed.
Among comorbidities and risk factors for venous and arterial thrombosis, there was significantly more frequent incidence of autoimmune diseases in the asymptomatic group of people compared to patients after thromboembolic episodes.
Most often the aAPA presence was confirmed in the LA tests – the majority of positive results appeared among patients with asymptomatic course and with past venous thrombosis as well and less frequently - in the group of arterial episodes in the history.
Any significant differences were found in the reference to the incidence of thrombotic episodes in the retrospective assessment of symptomatic patients and prospective – in the whole investigated group, although the time of their occurrence after beginning of observation period almost doubled in people with past thromboembolic episodes, comparing to the earlier asymptomatic persons.
Article Details
How to Cite
KOPYDŁOWSKA, Agata Lehmann et al.
Arterial and Venous Thrombosis as a Symptom of Antiphospholipid Syndrome – A Noticeable Analysis from the Past..
Medical Research Archives, [S.l.], v. 9, n. 3, mar. 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2359>. Date accessed: 16 apr. 2024.
doi: https://doi.org/10.18103/mra.v9i3.2359.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2. Heit JA, Cohen AT, Anderson FA Jr. On behalf of the VTE Impact Assessment Group. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood (ASH Annual Meeting Abstracts). 2005; 106: Abstr. 910.
3. Rand JH. The antiphospholipid syndrome. Pathogenic mechanisms, diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2003: 510-519.
4. Miyakis S, Lockshin MD, Atsumi T et al. International Consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4: 295-306.
5. Wisloff F, Jacobsen EM, Liestol S. Laboratory diagnosis of the antiphospholipid syndrome. Thromb Res. 2002; 108: 263-271.
6. Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009 ; 7(10):1737-1740.
7. Galli M, Luciani D, Bertolini G, Barbui T. Anti–β2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003;102 (8): 2717–2723
8. Galli M. The antiphospholipid triangle. J Thromb Haemost. 2010 Feb;8(2): 234-236.
9. Erkan D, Lockshin MD. New approaches for managing antiphospholipid syndrome. Nat Clin Pract Rheumatol. 2009 ; 5(3): 160-70.
10. Vianna JL, Khamashta MA, Ordi Ros J et al. Comparison of the primary and secondary antiphospholipid syndrome: A European Multicenter Study of 114 patients. Am J Med. 1994; 96 (1): 3-9.
11. Zawilska K. Antiphospholipid antibodies - risk factors for venous thromboembolism and arterial thrombosis. Pol Arch Med Wewn. 2007;117 Suppl: 41-45.
12. Ortel TL. Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2005: 462-468.
13. Zawilska K, Lehmann-Kopydłowska A. Clinically asymptomatic antiphospholipid antibodies - diagnostic and therapeutic problems. Pol Arch Med Wewn. 2008; 118 Suppl:70-74.
14. Galli M. Interpretation and recommended testing for antiphospholipid antibodies. Semin Thromb Hemost. 2012 Jun;38(4):348-52.
15. Devreese K, Hoylaerts MF. Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome. Eur J Haematol. 2009 Jul;83(1):1-16.
16. Asherson RA, Carvera R, de Groot PG et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003; 12: 530-534.
17. Musiał J. Antiphospholipid syndrome – magnifying glass of medicine. Pol Arch Med Wewn. 2007; 117 (1-2): 41-43.
18. Pierangeli SS, Chen PP, Gonzalez EB. Antphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisims. Curr Opin Hemat. 2006; 13: 366-375.
19. Pengo V, Bison E, Ruffati A, Iliceto S. Antibodies to oxidized LDL/2-glycoprotein I in antiphospholipid syndrome patients with venous and arterial thromboembolism. Thromb Res. 2008; 122 (4): 556-559.
20. Danowski A, de Azevedo MN, de Souza Papi JA, Petri M. Determinations of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and in antiphospholipid syndrome with systemic lupus erythematosus. J. Rheumatol. 2009; 36 (6) 1195 - 1199.
21. Erkan D, Lockshin MD. What is antiphospholipid syndrome? Curr Rheum Reports. 2004; 6: 451-457.
22. 17. Arnout J, Jankowski M. Antiphospholipid syndrome. Hematol J. 2004; 5 (suppl 3): S1-S5
23. De Laat B, Derksen RHWM, Urbanus RT et al. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of 2-glycoproteine I cause LAC and their presence correlates strongly with thrombosis. Blood. 2005; 105: 1540-1545.
24. Pengo V. Antiphospholipid syndrome: interpretation of laboratory data. J Thromb Haemost. 2011; 9: 402-403.
25. Reddel SW, Krillis SA. Testing for and clinical significance of anticardiolipin antibodies. Clin Diagn Lan Immunol. 1999; 6: 775-782
26. Čučnik S, Kveder T, Artenjak A et al. Avidity of anti-β2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Lupus. 2012 Jun; 21: 764-765.
27. Pengo V, Ruffati A, Legnani C et al. Clinical course of high risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010; 8: 237-242.
28. Metjian A, Lim W. ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis? Hematology Am Soc Hematol Educ Program. 2009:247-249.
29. Swadźba J, Iwaniec T, Szczeklik A. Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases. J Thromb Haemost. 2007; 5:1883-1889.
30. Bruce IN. "Not only...but also": factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology. 2005; 44: 1492-1502.
31. Calvo Alen J, Toloza SM, Fernandez M et al. Systematic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients. Arthritis Rheum. 2005; 44: 1492 - 1502.
32. Erkan D, Harrison MJ, Levy R. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Nat Clin Pract Rheumatol. 2008; 4: 14-15.
33. Giron-Gonzales JA, Garcia del Rio E, Rodriguez C et al. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004; 31: 1560 - 1567.
34. Pierangeli SS, Chen PP, Gonzalez EB. Antphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisims. Curr Opin Hemat. 2006; 13: 366-375.
35. Ruiz-Irastorza G., Crowther M., Branch W, Kamashta MA. Antiphospholipid syndrome. Lancet. 2010; 376: 1498-1509.
36. Goodnight SH, Griffin JH. Hereditary thrombophilia. Wiliams Haematology. 2001; 1697-1714
37. van der Meer FJ, Koster T, Vandenbroucke JP et al. The Leiden Thrombophilia Study (LETS). Thromb Haemost. 1997 Jul;78(1):631-5.
38. Oosting JD, Derksen RH, Bobbink IW et al. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood. 1993; 81: 2618-2625.
39. Pengo V. Antiphospholipid syndrome: interpretation of laboratory data. J Thromb Haemost. 2011; 9: 402-403.
40. Ho KT, Ahn W, Alarcon GS i wsp. Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombosis events. Rheumatology. 2005; 44: 1303-1307.
41. Erkan D, Harrison MJ, Levy R. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomised, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Nat Clin Pract Rheumatol. 2008; 4: 14-15.
42. Pengo V, Biasiolo A, Pegoraro C i wsp. Antibody profiles for the diagnosis of anriphospholipid syndrome. Thromb Haemost. 2005; 93: 1147 - 1152.
43. Pengo V, Biasiolo A, Gresele P i wsp. A comparison of lupus anticoagulant-positive patients with clinical picture of antiphospholipid syndrome and those without. Arterioscler Thromb Vasc Biol. 2007; 27: e309 - 310.
44. de Groot PG, Lutters B, Derksen RH i wsp. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005; 3: 1993 - 1997.
45. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulant are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systemic review of the literature. Blood. 2003; 101: 1540- 1545.
46. Rand JH. A snappy new concept for APS. Blood. 2010; 116 (8): 1193-1194.
47. Agar C, van Os GM, Mörgelin M et al. Beta2-glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood. 2010; 116: 1336-1343.
48. Urbanus RT, Siegierink B, Rosest M et al. Antiphospholipid antibodies and risk of myocardial infarction and ischemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 2009; 8: 998 - 1005.
49. Linnemann B, Schindewolf M, Zgouras D et al. Are patients with thrombophilia and previous venous thromboembolism at higher risk to arterial thrombosis? Thromb Res. 2008; 121: 743-745.
50. Ruffatti A, Tonello M, Del Ross T et al. Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity. Thromb Haemost. 2006; 96: 337 – 341
51. Giannakopoulos B, Passam F, Ioannou Y, Krillis SA. How we diagnose the antiphospholipid syndrome. Blood. 2009; 113: 985-994.
52. Pengo V, Ruffati A, Legnani C et al. Clinical course of high risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010; 8: 237-242.
53. Pengo V, Biasiolo A, Rampazzo P, Brocco T. dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-2-Glycoprotein I autoantibodies. Thromb Haemost. 1999; 81: 256 - 258.
54. Luters BC, Meiers JC, Derksen RH. Dimers of 2-glycoprotein I mimic the in vitro effects of 2-glycoprptein I-anti-2-glycoprotein I antibody complexes. J Biol Chem. 2001; 276:3060-3067.
55. Sikara MP, Routsias JG, Samiotaki M i wsp. β2 Glycoprotein I (β2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome. Blood. 2010; 115(3):713-23.
56. Galli M, Reber G, de Moerloose P. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost. 2008; 6: 399-401.
57. Wachal K, Majewski W, Kopydłowska A. The prevalence of primary antiphospholipid syndrome in patients with peripheral abnormalities in the upper and lower limbs. Acta Angiologica. 2008; 14 Suppl A: abstr. 16.
58. Erkan D, Lockshin MD. New approaches for managing antiphospholipid syndrome. Nat Clin Pract Rheumatol. 2009 ; 5(3): 160-70.
2. Heit JA, Cohen AT, Anderson FA Jr. On behalf of the VTE Impact Assessment Group. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood (ASH Annual Meeting Abstracts). 2005; 106: Abstr. 910.
3. Rand JH. The antiphospholipid syndrome. Pathogenic mechanisms, diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2003: 510-519.
4. Miyakis S, Lockshin MD, Atsumi T et al. International Consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4: 295-306.
5. Wisloff F, Jacobsen EM, Liestol S. Laboratory diagnosis of the antiphospholipid syndrome. Thromb Res. 2002; 108: 263-271.
6. Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009 ; 7(10):1737-1740.
7. Galli M, Luciani D, Bertolini G, Barbui T. Anti–β2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003;102 (8): 2717–2723
8. Galli M. The antiphospholipid triangle. J Thromb Haemost. 2010 Feb;8(2): 234-236.
9. Erkan D, Lockshin MD. New approaches for managing antiphospholipid syndrome. Nat Clin Pract Rheumatol. 2009 ; 5(3): 160-70.
10. Vianna JL, Khamashta MA, Ordi Ros J et al. Comparison of the primary and secondary antiphospholipid syndrome: A European Multicenter Study of 114 patients. Am J Med. 1994; 96 (1): 3-9.
11. Zawilska K. Antiphospholipid antibodies - risk factors for venous thromboembolism and arterial thrombosis. Pol Arch Med Wewn. 2007;117 Suppl: 41-45.
12. Ortel TL. Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2005: 462-468.
13. Zawilska K, Lehmann-Kopydłowska A. Clinically asymptomatic antiphospholipid antibodies - diagnostic and therapeutic problems. Pol Arch Med Wewn. 2008; 118 Suppl:70-74.
14. Galli M. Interpretation and recommended testing for antiphospholipid antibodies. Semin Thromb Hemost. 2012 Jun;38(4):348-52.
15. Devreese K, Hoylaerts MF. Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome. Eur J Haematol. 2009 Jul;83(1):1-16.
16. Asherson RA, Carvera R, de Groot PG et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003; 12: 530-534.
17. Musiał J. Antiphospholipid syndrome – magnifying glass of medicine. Pol Arch Med Wewn. 2007; 117 (1-2): 41-43.
18. Pierangeli SS, Chen PP, Gonzalez EB. Antphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisims. Curr Opin Hemat. 2006; 13: 366-375.
19. Pengo V, Bison E, Ruffati A, Iliceto S. Antibodies to oxidized LDL/2-glycoprotein I in antiphospholipid syndrome patients with venous and arterial thromboembolism. Thromb Res. 2008; 122 (4): 556-559.
20. Danowski A, de Azevedo MN, de Souza Papi JA, Petri M. Determinations of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and in antiphospholipid syndrome with systemic lupus erythematosus. J. Rheumatol. 2009; 36 (6) 1195 - 1199.
21. Erkan D, Lockshin MD. What is antiphospholipid syndrome? Curr Rheum Reports. 2004; 6: 451-457.
22. 17. Arnout J, Jankowski M. Antiphospholipid syndrome. Hematol J. 2004; 5 (suppl 3): S1-S5
23. De Laat B, Derksen RHWM, Urbanus RT et al. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of 2-glycoproteine I cause LAC and their presence correlates strongly with thrombosis. Blood. 2005; 105: 1540-1545.
24. Pengo V. Antiphospholipid syndrome: interpretation of laboratory data. J Thromb Haemost. 2011; 9: 402-403.
25. Reddel SW, Krillis SA. Testing for and clinical significance of anticardiolipin antibodies. Clin Diagn Lan Immunol. 1999; 6: 775-782
26. Čučnik S, Kveder T, Artenjak A et al. Avidity of anti-β2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Lupus. 2012 Jun; 21: 764-765.
27. Pengo V, Ruffati A, Legnani C et al. Clinical course of high risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010; 8: 237-242.
28. Metjian A, Lim W. ASH evidence-based guidelines: should asymptomatic patients with antiphospholipid antibodies receive primary prophylaxis to prevent thrombosis? Hematology Am Soc Hematol Educ Program. 2009:247-249.
29. Swadźba J, Iwaniec T, Szczeklik A. Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases. J Thromb Haemost. 2007; 5:1883-1889.
30. Bruce IN. "Not only...but also": factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology. 2005; 44: 1492-1502.
31. Calvo Alen J, Toloza SM, Fernandez M et al. Systematic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients. Arthritis Rheum. 2005; 44: 1492 - 1502.
32. Erkan D, Harrison MJ, Levy R. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Nat Clin Pract Rheumatol. 2008; 4: 14-15.
33. Giron-Gonzales JA, Garcia del Rio E, Rodriguez C et al. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004; 31: 1560 - 1567.
34. Pierangeli SS, Chen PP, Gonzalez EB. Antphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisims. Curr Opin Hemat. 2006; 13: 366-375.
35. Ruiz-Irastorza G., Crowther M., Branch W, Kamashta MA. Antiphospholipid syndrome. Lancet. 2010; 376: 1498-1509.
36. Goodnight SH, Griffin JH. Hereditary thrombophilia. Wiliams Haematology. 2001; 1697-1714
37. van der Meer FJ, Koster T, Vandenbroucke JP et al. The Leiden Thrombophilia Study (LETS). Thromb Haemost. 1997 Jul;78(1):631-5.
38. Oosting JD, Derksen RH, Bobbink IW et al. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood. 1993; 81: 2618-2625.
39. Pengo V. Antiphospholipid syndrome: interpretation of laboratory data. J Thromb Haemost. 2011; 9: 402-403.
40. Ho KT, Ahn W, Alarcon GS i wsp. Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombosis events. Rheumatology. 2005; 44: 1303-1307.
41. Erkan D, Harrison MJ, Levy R. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomised, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Nat Clin Pract Rheumatol. 2008; 4: 14-15.
42. Pengo V, Biasiolo A, Pegoraro C i wsp. Antibody profiles for the diagnosis of anriphospholipid syndrome. Thromb Haemost. 2005; 93: 1147 - 1152.
43. Pengo V, Biasiolo A, Gresele P i wsp. A comparison of lupus anticoagulant-positive patients with clinical picture of antiphospholipid syndrome and those without. Arterioscler Thromb Vasc Biol. 2007; 27: e309 - 310.
44. de Groot PG, Lutters B, Derksen RH i wsp. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005; 3: 1993 - 1997.
45. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulant are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systemic review of the literature. Blood. 2003; 101: 1540- 1545.
46. Rand JH. A snappy new concept for APS. Blood. 2010; 116 (8): 1193-1194.
47. Agar C, van Os GM, Mörgelin M et al. Beta2-glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood. 2010; 116: 1336-1343.
48. Urbanus RT, Siegierink B, Rosest M et al. Antiphospholipid antibodies and risk of myocardial infarction and ischemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 2009; 8: 998 - 1005.
49. Linnemann B, Schindewolf M, Zgouras D et al. Are patients with thrombophilia and previous venous thromboembolism at higher risk to arterial thrombosis? Thromb Res. 2008; 121: 743-745.
50. Ruffatti A, Tonello M, Del Ross T et al. Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity. Thromb Haemost. 2006; 96: 337 – 341
51. Giannakopoulos B, Passam F, Ioannou Y, Krillis SA. How we diagnose the antiphospholipid syndrome. Blood. 2009; 113: 985-994.
52. Pengo V, Ruffati A, Legnani C et al. Clinical course of high risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010; 8: 237-242.
53. Pengo V, Biasiolo A, Rampazzo P, Brocco T. dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-2-Glycoprotein I autoantibodies. Thromb Haemost. 1999; 81: 256 - 258.
54. Luters BC, Meiers JC, Derksen RH. Dimers of 2-glycoprotein I mimic the in vitro effects of 2-glycoprptein I-anti-2-glycoprotein I antibody complexes. J Biol Chem. 2001; 276:3060-3067.
55. Sikara MP, Routsias JG, Samiotaki M i wsp. β2 Glycoprotein I (β2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome. Blood. 2010; 115(3):713-23.
56. Galli M, Reber G, de Moerloose P. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost. 2008; 6: 399-401.
57. Wachal K, Majewski W, Kopydłowska A. The prevalence of primary antiphospholipid syndrome in patients with peripheral abnormalities in the upper and lower limbs. Acta Angiologica. 2008; 14 Suppl A: abstr. 16.
58. Erkan D, Lockshin MD. New approaches for managing antiphospholipid syndrome. Nat Clin Pract Rheumatol. 2009 ; 5(3): 160-70.