Jornal Vascular Brasileiro
https://jvascbras.org/article/doi/10.1590/1677-5449.011416
Jornal Vascular Brasileiro
Review Article

A importância de reconhecer a síndrome antifosfolípide na medicina vascular

The importance of recognizing antiphospholipid syndrome in vascular medicine

Andreas Funke, Adriana Danowski, Danieli Castro Oliveira de Andrade, Jozelia Rêgo, Roger Abramino Levy

Downloads: 1
Views: 1205

Resumo

A síndrome antifosfolipíde (SAF) é uma doença autoimune sistêmica caracterizada por trombose arterial ou venosa recorrente e/ou morbidade gestacional e pela presença dos anticorpos antifosfolipídeos, podendo apresentar outras manifestações vasculares, como microangiopatia, arteriopatia crônica e SAF catastrófica. Determinados testes laboratoriais para a síndrome (por exemplo, o anticoagulante lúpico) podem sofrer interferência do uso de medicações anticoagulantes, dificultando o diagnóstico. A fisiopatologia da SAF é complexa, sendo enumerados no texto diversos mecanismos patogênicos relacionados à coagulação, ao endotélio e às plaquetas. Por fim, discutimos o tratamento da SAF de acordo com a presença e o tipo de manifestações clínicas, o uso dos anticoagulantes orais diretos e o manejo perioperatório de pacientes com SAF.

Palavras-chave

síndrome antifosfolípide; anticoagulante do lúpus; anticorpos anticardiolipina; trombose; autoimunidade.

Abstract

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent arterial or venous thrombosis and/or gestational morbidity and by the presence of antiphospholipid antibodies. It can also cause other vascular manifestations such as microangiopathy, chronic arteriopathy and catastrophic APS (CAPS). Certain laboratory tests for the syndrome (for example, the lupus anticoagulant test) can be affected by the use of anticoagulant agents, making diagnosis more difficult. The pathophysiology of APS is complex, and several mechanisms of pathogenesis related to coagulation, endothelium, and platelets are discussed in this article. We conclude by discussing treatment of APS according to the presence and type of clinical manifestations, use of direct oral anticoagulants (DOAs), and perioperative management of patients with APS.

Keywords

antiphospholipid syndrome; lupus anticoagulant; anticardiolipin antibodies; thrombosis; autoimmunity

References

1. Merashli M, Noureldine MHA, Uthman I, Khamashta M. Antiphospholipid syndrome: an update. Eur J Clin Invest. 2015;45(6):653-62. PMid:25851448. http://dx.doi.org/10.1111/eci.12449.

2. Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun. 2014;48-49:20-5. PMid:24461539. http://dx.doi.org/10.1016/j.jaut.2014.01.006.

3. Pons-Estel GJ, Cervera R. Renal involvement in antiphospholipid syndrome. Curr Rheumatol Rep. 2014;16(2):397. PMid:24357443. http://dx.doi.org/10.1007/s11926-013-0397-0.

4. Christodoulou C, Sangle S, D’Cruz DP. Vasculopathy and arterial stenotic lesions in the antiphospholipid syndrome. Rheumatology. 2007;46(6):907-10. PMid:17403711. http://dx.doi.org/10.1093/rheumatology/kem040.

5. Belizna CC, Richard V, Primard E, et al. Early atheroma in primary and secondary antiphospholipid syndrome: an intrinsic finding. Semin Arthritis Rheum. 2008;37(6):373-80. PMid:17977581. http://dx.doi.org/10.1016/j.semarthrit.2007.08.002.

6. Ames PRJ, Margarita A, Alves JD. Antiphospholipid antibodies and atherosclerosis: insights from systemic lupus erythematosus and primary antiphospholipid syndrome. Clin Rev Allergy Immunol. 2009;37(1):29-35. PMid:18987784. http://dx.doi.org/10.1007/s12016-008-8099-5.

7. Denas G, Jose SP, Bracco A, Zoppellaro G, Pengo V. Antiphospholipid syndrome and the heart: a case series and literature review. Autoimmun Rev. 2015;14(3):214-22. PMid:25461836. http://dx.doi.org/10.1016/j.autrev.2014.11.003.

8. Cervera R, Piette J-C, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019-27. PMid:11953980. http://dx.doi.org/10.1002/art.10187.

9. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010;376(9751):1498-509. PMid:20822807. http://dx.doi.org/10.1016/S0140-6736(10)60709-X.

10. Asherson RA, Cervera R, de Groot PG, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003;12(7):530-4. PMid:12892393. http://dx.doi.org/10.1191/0961203303lu394oa.

11. Cervera R, Rodríguez-Pintó I, Colafrancesco S, et al. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Autoimmun Rev. 2014;13(7):699-707. PMid:24657970. http://dx.doi.org/10.1016/j.autrev.2014.03.002.

12. 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(2):295-306. PMid:16420554. http://dx.doi.org/10.1111/j.1538-7836.2006.01753.x.

13. Meroni PL, Chighizola CB, Rovelli F, Gerosa M. Antiphospholipid syndrome in 2014: more clinical manifestations, novel pathogenic players and emerging biomarkers. Arthritis Res Ther. 2014;16(2):209. PMid:25166960. http://dx.doi.org/10.1186/ar4549.

14. Rodríguez-García V, Ioannou Y, Fernández-Nebro A, Isenberg DA, Giles IP. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology. 2015;54(11):2042-50. PMid:26152548. http://dx.doi.org/10.1093/rheumatology/kev226.

15. 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):1737-40. PMid:19624461. http://dx.doi.org/10.1111/j.1538-7836.2009.03555.x.

16. Savino S, Breen K, Hunt BJ. Rivaroxaban use in patients with antiphospholipid syndrome and previous venous thromboembolism. Blood Coagul Fibrinolysis. 2015;26(4):476-7. PMid:25923780. http://dx.doi.org/10.1097/MBC.0000000000000247.

17. Arachchillage DJ, Cohen H. Use of new oral anticoagulants in antiphospholipid syndrome. Curr Rheumatol Rep. 2013;15(6):331. PMid:23649961. http://dx.doi.org/10.1007/s11926-013-0331-5.

18. Van Os GMA, de Laat B, Kamphuisen PW, Meijers JCM, de Groot PG. Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time. J Thromb Haemost JTH. 2011;9(8):1657-9. PMid:21668740. http://dx.doi.org/10.1111/j.1538-7836.2011.04395.x.

19. Góralczyk T, Iwaniec T, Wypasek E, Undas A. False-positive lupus anticoagulant in patients receiving rivaroxaban: 24h since the last dose are needed to exclude antiphospholipid syndrome. Blood Coagul Fibrinolysis. 2015;26(4):473-5. PMid:25402189. http://dx.doi.org/10.1097/MBC.0000000000000235.

20. Chaturvedi S, Cockrell E, Espinola R, et al. Circulating microparticles in patients with antiphospholipid antibodies: characterization and associations. Thromb Res. 2015;135(1):102-8. PMid:25467081. http://dx.doi.org/10.1016/j.thromres.2014.11.011.

21. Breen KA, Sanchez K, Kirkman N, et al. Endothelial and platelet microparticles in patients with antiphospholipid antibodies. Thromb Res. 2015;135(2):368-74. PMid:25496997. http://dx.doi.org/10.1016/j.thromres.2014.11.027.

22. Giannakopoulos B, Krilis SA. The pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368(11):1033-44. PMid:23484830. http://dx.doi.org/10.1056/NEJMra1112830.

23. Canaud G, Bienaimé F, Tabarin F, et al. Inhibition of the mTORC pathway in the antiphospholipid syndrome. N Engl J Med. 2014;371(4):303-12. PMid:25054716. http://dx.doi.org/10.1056/NEJMoa1312890.

24. Jesus GRR, dos Santos FC, Oliveira CS, Mendes-Silva W, Jesus NR, Levy RA. Management of obstetric antiphospholipid syndrome. Curr Rheumatol Rep. 2012;14(1):79-86. PMid:22105547. http://dx.doi.org/10.1007/s11926-011-0218-2.

25. Galarza-Maldonado C, Kourilovitch MR, Pérez-Fernández OM, et al. Obstetric antiphospholipid syndrome. Autoimmun Rev. 2012;11(4):288-95. PMid:22001418. http://dx.doi.org/10.1016/j.autrev.2011.10.006.

26. Danowski A, Rego J, Kakehasi AM, et al. Diretrizes para o tratamento da síndrome do anticorpo antifosfolipídeo. Rev Bras Reumatol. 2013;53(2):184-92. PMid:23856795. http://dx.doi.org/10.1590/S0482-50042013000200005.

27. Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus. 2011;20(2):206-18. PMid:21303837. http://dx.doi.org/10.1177/0961203310395803.

28. Erkan D, Harrison MJ, Levy R, et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, doubleblind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum. 2007;56(7):2382-91. PMid:17599766. http://dx.doi.org/10.1002/art.22663.

29. Arnaud L, Mathian A, Ruffatti A, et al. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis. Autoimmun Rev. 2014;13(3):281-91. PMid:24189281. http://dx.doi.org/10.1016/j.autrev.2013.10.014.

30. Arnaud L, Mathian A, Devilliers H, et al. Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies. Autoimmun Rev. 2015;14(3):192-200. PMid:25461472. http://dx.doi.org/10.1016/j.autrev.2014.10.019.

31. Rosborough TK, Jacobsen JM, Shepherd MF. Factor X and factor II activity levels do not always agree in warfarin-treated lupus anticoagulant patients. Blood Coagul Fibrinolysis. 2010;21(3):242-4. PMid:20182349. http://dx.doi.org/10.1097/MBC.0b013e32833581a3.

32. Tahir F, Riaz H, Riaz T, et al. The new oral anti-coagulants and the phase 3 clinical trials: a systematic review of the literature. Thromb J. 2013;11(1):18. PMid:24007323. http://dx.doi.org/10.1186/1477-9560-11-18.

33. Kakkos SK, Kirkilesis GI, Tsolakis IA. Editor’s Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg. 2014;48(5):565-75. PMid:24951377. http://dx.doi.org/10.1016/j.ejvs.2014.05.001.

34. Cohen AT, Hamilton M, Bird A, et al. Comparison of the non-VKA oral anticoagulants apixaban, dabigatran, and rivaroxaban in the extended treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. PLoS One. 2016;11(8):e0160064. PMid:27487187. http://dx.doi.org/10.1371/journal.pone.0160064.

35. Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Jesus GR, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res. 2013;65(11):1869-73. PMid:23861221. http://dx.doi.org/10.1002/acr.22066.

36. Cohen H, Doré CJ, Clawson S, et al. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE. Lupus. 2015;24(10):1087-94. PMid:25940537. http://dx.doi.org/10.1177/0961203315581207.

37. ClinicalTrials.gov [site na Internet]. Rivaroxaban in Thrombotic Antiphospholipid Syndrome (TRAPS). USA; 2014. [citado 2015 nov 7]. https://clinicaltrials.gov/ct2/show/record/NCT02157272

38. Noel N, Dutasta F, Costedoat-Chalumeau N, et al. Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome. Autoimmun Rev. 2015;14(8):680-5. PMid:25864630. http://dx.doi.org/10.1016/j.autrev.2015.03.007.

39. Schaefer JK, McBane RD, Black DF, Williams LN, Moder KG, Wysokinski WE. Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients. Thromb Haemost. 2014;112(5):947-50. PMid:25118790. http://dx.doi.org/10.1160/TH14-03-0272.

40. Win K, Rodgers GM. New oral anticoagulants may not be effective to prevent venous thromboembolism in patients with antiphospholipid syndrome. Am J Hematol. 2014;89(10):1017. PMid:25043836. http://dx.doi.org/10.1002/ajh.23797.

41. Signorelli F, Nogueira F, Domingues V, Mariz HA, Levy RA. Thrombotic events in patients with antiphospholipid syndrome treated with rivaroxaban: a series of eight cases. Clin Rheumatol. 2016;35(3):801-5. PMid:26219490.

42. Erkan D, Aguiar CL, Andrade D, et al. 14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends. Autoimmun Rev. 2014;13(6):685-96. PMid:24468415. http://dx.doi.org/10.1016/j.autrev.2014.01.053.

43. Rodriguez-Pintó I, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: The current management approach. Best Pract Res Clin Rheumatol. 2016;30(2):239-49. PMid:27886797. http://dx.doi.org/10.1016/j.berh.2016.07.004.

44. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clinical and laboratory features of 50 patients. Medicine. 1998;77(3):195-207. PMid:9653431. http://dx.doi.org/10.1097/00005792-199805000-00005.

45. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine. 2001;80(6):355-77. PMid:11704713. http://dx.doi.org/10.1097/00005792-200111000-00002.

46. Saunders KH, Erkan D, Lockshin MD. Perioperative management of antiphospholipid antibody-positive patients. Curr Rheumatol Rep. 2014;16(7):426. PMid:24828479. http://dx.doi.org/10.1007/s11926-014-0426-7.

47. Erkan D, Yazici Y, Peterson MG, Sammaritano L, Lockshin MD. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology. 2002;41(8):924-9. PMid:12154210. http://dx.doi.org/10.1093/rheumatology/41.8.924.

48. Akkara Veetil BM, Bongartz T. Perioperative care for patients with rheumatic diseases. Nat Rev Rheumatol. 2011;8(1):32-41. PMid:22083219. http://dx.doi.org/10.1038/nrrheum.2011.171.

49. Arkfeld DG, Weitz IC. Immune thrombocytopenia in patients with connective tissue disorders and the antiphospholipid antibody syndrome. Hematol Oncol Clin North Am. 2009;23(6):1239-49. PMid:19932431. http://dx.doi.org/10.1016/j.hoc.2009.08.010.

50. Mazodier K, Arnaud L, Mathian A, et al. Lupus anticoagulanthypoprothrombinemia syndrome: report of 8 cases and review of the literature. Medicine. 2012;91(5):251-60. PMid:22932789. http://dx.doi.org/10.1097/MD.0b013e31826b971f.

51. Orfanakis A, Deloughery T. Patients with disorders of thrombosis and hemostasis. Med Clin North Am. 2013;97(6):1161-80. PMid:24182725. http://dx.doi.org/10.1016/j.mcna.2013.07.004.

Sociedade Brasileira de Angiologia e Cirurgia Vascular (SBACV)"> Sociedade Brasileira de Angiologia e Cirurgia Vascular (SBACV)">
5cd475bf0e88252d297f3257 jvb Articles

J Vasc Bras

Share this page
Page Sections