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Use of Hydroxychloroquine to Prevent Thrombosis in Systemic Lupus Erythematosus and in Antiphospholipid Antibody–Positive Patients

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Abstract

Hydroxychloroquine is used extensively in the treatment of systemic lupus erythematosus, not only for its benefit for cutaneous and musculoskeletal lupus, but also for its role in preventing flares, preventing renal and central nervous system lupus, and improving survival rates. Hydroxychloroquine also has known benefits in reducing some traditional cardiovascular risk factors, such as hyperlipidemia and diabetes mellitus. This article reviews its possible role as an antithrombotic drug in the general population, in systemic lupus erythematosus, and in patients with antiphospholipid antibodies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Madow BP: Use of anti-malarial drugs as “desludging” agents in vascular disease processes. JAMA 1960, 172:1630–1633.

    CAS  Google Scholar 

  2. Cecchi E, Ferraris D: Desludging action of hydroxychloroquine in rheumatoid arthritis. Acta Rheumatol Scand 1962, 8:214–221.

    Article  Google Scholar 

  3. Ernst E, Rose M, Lee R: Modification of trans-operative changes in blood fluidity by hydroxy-chloroquine. A possible explanation for the drugs anti-thrombotic effect. Pharmatherapeutica 1984, 4:48–52.

    CAS  PubMed  Google Scholar 

  4. Bird HA, Harkness J, Wright V: Some rheological properties of blood during anti-rheumatoid therapy. Pharmatherapeutica 1981, 3:36–39.

    CAS  PubMed  Google Scholar 

  5. Winocour PD, Kinlough-Rathbone RL, Mustard JF: The effect of the phospholipase inhibitor mepacrine on platelet aggregation, the platelet release reaction and fibrinogen binding to the platelet surface. Thromb Haemost 1981, 45:257–262.

    CAS  PubMed  Google Scholar 

  6. Carter AE, Eban R, Perrett RD: Prevention of post-operative deep venous thrombosis and pulmonary embolism. Br Med J 1971, 1:312–314.

    Article  CAS  PubMed  Google Scholar 

  7. Kinlough-Rathbone RL: Platelets, Drugs and Thrombosis. The Effects of Some Other Drugs in Platelet Function. Basel, Switzerland: Karger; 1975.

  8. Espinola RG, Pierangeli SS, Gharavi AE, Harris EN: Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 2002, 87:518–522.

    CAS  PubMed  Google Scholar 

  9. Rand JH, Wu XX, Quinn AS, et al.: Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood 2008, 112:1687–1695.

    Article  CAS  PubMed  Google Scholar 

  10. Rand JH, Wu XX, Quinn AS, et al.: Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug. Blood 2010, 115:2292–2299.

    Article  CAS  PubMed  Google Scholar 

  11. Rosenberg FJ, Phillips PG, Druzba PG: Use of a rabbit extracarporeal shunt in the assay of antithrombotic and thrombotic drugs. In Platelets and Thrombosis. Baltimore, MD: Baltimore University Park Press; 1974:233–234.

  12. Ziegler HK, Unanue ER: Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A 1982, 79:175–178.

    Article  CAS  PubMed  Google Scholar 

  13. Fox RI, Kang H-I: Mechanism of action of antimalarial drugs: inhibition of antigen processing and presentation. Lupus 1993, 2(Suppl 1):S9–S12.

    Article  CAS  PubMed  Google Scholar 

  14. Lafyatis R, York M, Marshak-Rothstein A: Antimalarial agents: closing the gate on Toll-like receptors? Arthritis Rheum 2006, 54:3068–3070.

    Article  CAS  PubMed  Google Scholar 

  15. Kyburz D, Brentano F, Gay S: Mode of action of hydroxychloroquine in RA—evidence of an inhibitory effect on Toll-like receptor signaling. Nat Clin Pract Rheumatol 2006, 2:458–459.

    Article  PubMed  Google Scholar 

  16. Raschi E, Borghi MO, Grossi C, et al.: Toll-like receptors: another player in the pathogenesis of the anti-phospholipid syndrome. Lupus 2008, 17:937–942.

    Article  CAS  PubMed  Google Scholar 

  17. Salmeron G, Lipsky PE: Immunosuppressive potential of antimalarials. Am J Med 1983, 75(Suppl):19–24.

    Article  CAS  PubMed  Google Scholar 

  18. Wallace DJ, Linker-Israeli M, Hyun S, et al.: The effect of hydroxychloroquine therapy on serum levels of immunoregulatory molecules in patients with systemic lupus erythematosus. J Rheumatol 1994, 21:375–376.

    CAS  PubMed  Google Scholar 

  19. van den Borne BE, Dijkmans BA, de Rooij HH, et al.: Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol 1997, 24:55–60.

    PubMed  Google Scholar 

  20. Weber SM, Levitz SM: Chloroquine interferes with lipopolysaccharide-induced TNF-alpha gene expression by a nonlysosomotropic mechanism. J Immunol 2000, 165:1534–1540.

    CAS  PubMed  Google Scholar 

  21. Bygbjerg IC, Svenson M, Theander TG, Bendtzen K: Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes. Int J Immunopharmacol 1987, 9:513–519.

    Article  CAS  PubMed  Google Scholar 

  22. Sorice M, Longo A, Capozzi A, et al.: Anti-beta2-glycoprotein I antibodies induce monocyte release of tumor necrosis factor alpha and tissue factor by signal transduction pathways involving lipid rafts. Arthritis Rheum 2007, 56:2687–2697.

    Article  CAS  PubMed  Google Scholar 

  23. Doring Y, Hurst J, Lorenz M, et al.: Human antiphospholipid antibodies induce TNFalpha in monocytes via Toll-like receptor 8. Immunobiology 2010, 215:230–241.

    Article  PubMed  Google Scholar 

  24. Berman J, Girardi G, Salmon JE: TNF-alpha is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. J Immunol 2005, 174:485–490.

    CAS  PubMed  Google Scholar 

  25. Goldman FD, Gilman AL, Hollenback C, et al.: Hydroxychloroquine inhibits calcium signals in T cells: a new mechanism to explain its immunomodulatory properties. Blood 2000, 95:3460–3466.

    CAS  PubMed  Google Scholar 

  26. Fontagne J, Roch-Arveiller M, Giroud JP, Lechat P: Effects of some antimalarial drugs on rat inflammatory polymorphonuclear leukocyte function. Biomed Pharmacother 1989, 43:43–51.

    Article  CAS  PubMed  Google Scholar 

  27. Segal-Eiras A, Segura GM, Babini JC, et al.: Effect of antimalarial treatment on circulating immune complexes in rheumatoid arthritis. J Rheumatol 1985, 12:87–89.

    CAS  PubMed  Google Scholar 

  28. Edwards MH, Pierangeli S, Liu X, et al.: Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation 1997, 96:4380–4384.

    CAS  PubMed  Google Scholar 

  29. Carter AE, Eban R: Prevention of postoperative deep venous thrombosis in legs by orally administered hydroxychloroquine sulphate. Br Med J 1974, 3:94–95.

    Article  CAS  PubMed  Google Scholar 

  30. Wu TK, Tsapogas MJ, Jordan FR: Prophylaxis of deep venous thrombosis by hydroxychloroquine sulfate and heparin. Surg Gynecol Obstet 1977, 145:714–718.

    CAS  PubMed  Google Scholar 

  31. Johnson R, Charnley J: Hydroxychloroquine in prophylaxis of pulmonary embolism following hip arthroplasty. Clin Orthoped 1979, 144:174–177.

    Google Scholar 

  32. Chrisman DO, Snook GA, Wilson TC, Short JY: Prevention of venous thromboembolism by administration of hydroxychloroquine. J Bone Joint Surg 1976, 58A:918–920.

    Google Scholar 

  33. Hansen EH, Jessing P, Lindewald H, et al.: Hydroxychloroquine sulphate in prevention of deep venous thrombosis following fracture of the hip, pelvis or thoracolumbar spine. J Bone Joint Surg 1976, 58A:1089–1093.

    Google Scholar 

  34. Sanchez-Guerrero J, Fragoso-Loyo HE, Neuwelt CM, et al.: Effects of prasterone on bone mineral density in women with active systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol 2008, 35:1567–1575.

    CAS  PubMed  Google Scholar 

  35. Johansson E, Forsberg K, Johnsson H: Clinical and experimental evaluation of the thromboprophylactic effect of hydroxychloroquine sulfate after total hip replacement. Haemostasis 1981, 10:89–96.

    CAS  PubMed  Google Scholar 

  36. Cooke ED, Dawson MHO, Ibbotson RM, et al.: Failure of orally administered hydroxychloroquine sulphate to prevent venous thromboembolism following elective hip operations. J Bone Joint Surg 1977, 59A:496–500.

    Google Scholar 

  37. Loudon JR: Hydroxychloroquine and postoperative thromboembolism after total hip replacement. Am J Med 1988, 85(Suppl 4A):57–61.

    Article  CAS  PubMed  Google Scholar 

  38. Wallace D: Does hydroxychloroquine sulfate prevent clot formation in systemic lupus erythematosus? [letter]. Arthritis Rheum 1987, 30:1435–1436.

    Article  CAS  PubMed  Google Scholar 

  39. Petri M, Hellmann D, Hochberg M, et al.: Arterial thrombotic events (TE) in SLE: the Baltimore Lupus Cohort study [abstract]. Arthritis Rheum 1994, 37(Suppl 9):S297.

    Google Scholar 

  40. Ruiz-Irastorza G, Egurbide MV, Pijoan JI, et al.: Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 2006, 15:577–583.

    Article  CAS  PubMed  Google Scholar 

  41. • Tektonidou MG, Laskari K, Panagiotakos DB, Moutsopoulos HM: Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum 2009, 61:29–36. This was a case-control study showing that aspirin and HCQ are both protective (P=0.05) against thrombosis in antiphospholipid antibody–positive SLE patients.

    PubMed  Google Scholar 

  42. • Jung H, Bobba R, Su J, et al.: The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum 2010, 62:863–868. This recent nested case-control study confirmed that HCQ is protective against thrombosis, adjusting for disease severity, disease duration, and calendar year.

    Article  CAS  PubMed  Google Scholar 

  43. Erkan D, Yazici Y, Peterson MG, et al.: A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 2002, 41:924–929.

    Article  CAS  Google Scholar 

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  1. Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 7500, Baltimore, MD, 21205, USA

    Michelle Petri

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  1. Michelle Petri
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Correspondence to Michelle Petri.

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Petri, M. Use of Hydroxychloroquine to Prevent Thrombosis in Systemic Lupus Erythematosus and in Antiphospholipid Antibody–Positive Patients. Curr Rheumatol Rep 13, 77–80 (2011). https://doi.org/10.1007/s11926-010-0141-y

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