Blood Reviews
Volume 22, Issue 4 , Pages 187-194 , July 2008

The Hematologic Manifestations of the Antiphospholipid Syndrome

  • Imad Uthman

      Affiliations

    • Division of Rheumatology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
    • Corresponding Author InformationCorresponding author. Tel.: +961 3 379098; fax: +961 1 744464.
    • ,
  • Bertrand Godeau

      Affiliations

    • Service de Médecine Interne, CHU Henri Mondor, Assistance Publique, Hôpitaux de Paris, Université Paris 12, Créteil, France
    • ,
  • Ali Taher

      Affiliations

    • Division of Hematology and oncology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
    • ,
  • Munther Khamashta

      Affiliations

    • Senior Lecturer/Consultant Physician, Lupus Research Unit, The Rayne Institute, Guy’s, King’s and St. Thomas’ School of Medicine, St. Thomas’ Hospital, London, UK

References 

  1. Khamashta MA, Bertolaccini ML, Hughes GR. Antiphospholipid (Hughes) syndrome. Autoimmunity. 2004;37:309–312
  2. Vermylen J, Carreras LO, Arnout J. Attempts to make sense of the antiphospholipid syndrome. J Thromb Haemost. 2007;5:1–4
  3. Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19:265–275
  4. Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. A study of 25 cases and review of the literature. Haemostasis. 1985;15:254–262
  5. Harris EN, Chan JK, Asherson RA, Aber VR, Gharavi AE, Hughes GR. Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test. Arch Intern Med. 1986;146:2153–2156
  6. Deleze M, Alarcon-Segovia D, Oria CV, Sanchez-Guerrero J, Fernandez-Dominguez L, Gomez-Pacheco L, et al. Hemocytopenia in systemic lupus erythematosus. Relationship to antiphospholipid antibodies. J Rheumatol. 1989;16:926–930
  7. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore). 1993;72:113–124
  8. Cuadrado MJ, Mujic F, Munoz E, Khamashta MA, Hughes GR. Thrombocytopenia in the antiphospholipid syndrome. Ann Rheum Dis. 1997;56:194–196
  9. Krause I, Blank M, Fraser A, Lorber M, Stojanovich L, Rovensky J, et al. The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome. Immunobiology. 2005;210:749–754
  10. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019–1027
  11. Thrombosis and thrombocytopenia in antiphospholipid syndrome (idiopathic and secondary to SLE): first report from the Italian Registry. Italian Registry of Antiphospholipid Antibodies (IR-APA). Haematologica 1993;78:313-318.
  12. Galli M, Finazzi G, Barbui T. Thrombocytopenia in the antiphospholipid syndrome: pathophysiology, clinical relevance and treatment. Ann Med Interne (Paris). 1996;147(Suppl 1):24–27
  13. Martin H, Khamashta MA. Thrombocytopenia in the antiphospholipid syndrome. Med Clin (Barc). 1998;111:776–778
  14. Kaufman LD, Gomez-Reino JJ, Heinicke MH, Gorevic PD. Male lupus: retrospective analysis of the clinical and laboratory features of 52 patients, with a review of the literature. Semin Arthritis Rheum. 1989;18:189–197
  15. Miller MH, Urowitz MB, Gladman DD, Killinger DW. Systemic lupus erythematosus in males. Medicine (Baltimore). 1983;62:327–334
  16. Sthoeger ZM, Geltner D, Rider A, Bentwich Z. Systemic lupus erythematosus in 49 Israeli males: a retrospective study. Clin Exp Rheumatol. 1987;5:233–240
  17. Ward MM, Studenski S. Systemic lupus erythematosus in men: a multivariate analysis of gender differences in clinical manifestations. J Rheumatol. 1990;17:220–224
  18. Hochberg MC, Boyd RE, Ahearn JM, Arnett FC, Bias WB, Provost TT, et al. Systemic lupus erythematosus: a review of clinico-laboratory features and immunogenetic markers in 150 patients with emphasis on demographic subsets. Medicine (Baltimore). 1985;64:285–295
  19. Blum A, Rubinow A, Galun E. Predominance of renal involvement in male patients with systemic lupus erythematosus. Clin Exp Rheumatol. 1991;9:206–207
  20. Atsumi T, Furukawa S, Amengual O, Koike T. Antiphospholipid antibody associated thrombocytopenia and the paradoxical risk of thrombosis. Lupus. 2005;14:499–504
  21. Arnout J. The pathogenesis of the antiphospholipid syndrome: a hypothesis based on parallelisms with heparin-induced thrombocytopenia. Thromb Haemost. 1996;75:536–541
  22. Harris EN, Asherson RA, Gharavi AE, Morgan SH, Derue G, Hughes GR. Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody. Br J Haematol. 1985;59:227–230
  23. Out HJ, de Groot PG, van Vliet M, de Gast GC, Nieuwenhuis HK, Derksen RH. Antibodies to platelets in patients with anti-phospholipid antibodies. Blood. 1991;77:2655–2659
  24. Khamashta MA, Harris EN, Gharavi AE, Derue G, Gil A, Vazquez JJ, et al. Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes. Ann Rheum Dis. 1988;47:849–854
  25. Rote NS, Ng AK, Dostal-Johnson DA, Nicholson SL, Siekman R. Immunologic detection of phosphatidylserine externalization during thrombin-induced platelet activation. Clin Immunol Immunopathol. 1993;66:193–200
  26. Alarcon-Segovia D, Cabral AR. Antiphospholipid antibodies. Where do they come from? Where do they go?. J Rheumatol. 1994;21:982–989
  27. Galli M, Daldossi M, Barbui T. Anti-glycoprotein Ib/IX and IIb/IIIa antibodies in patients with antiphospholipid antibodies. Thromb Haemost. 1994;71:571–575
  28. Kiefel V, Santoso S, Kaufmann E, Mueller-Eckhardt C. Autoantibodies against platelet glycoprotein Ib/IX: a frequent finding in autoimmune thrombocytopenic purpura. Br J Haematol. 1991;79:256–262
  29. Godeau B, Piette JC, Fromont P, Intrator L, Schaeffer A, Bierling P. Specific antiplatelet glycoprotein autoantibodies are associated with the thrombocytopenia of primary antiphospholipid syndrome. Br J Haematol. 1997;98:873–879
  30. Macchi L, Rispal P, Clofent-Sanchez G, Pellegrin JL, Nurden P, Leng B, et al. Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia. Br J Haematol. 1997;98:336–341
  31. Panzer S, Gschwandtner ME, Hutter D, Spitzauer S, Pabinger I. Specificities of platelet autoantibodies in patients with lupus anticoagulants in primary antiphospholipid syndrome. Ann Hematol. 1997;74:239–242
  32. Nakamura M, Tanaka Y, Satoh T, Kawai M, Hirakata M, Kaburaki J, et al. Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism. Rheumatology (Oxford). 2006;45:150–156
  33. Nojima J, Suehisa E, Kuratsune H, Machii T, Koike T, Kitani T, et al. Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus--possible association with thrombotic and thrombocytopenic complications. Thromb Haemost. 1999;81:436–441
  34. Martinuzzo ME, Maclouf J, Carreras LO, Levy-Toledano S. Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation. Thromb Haemost. 1993;70:667–671
  35. Alliot C, Messouak D, Albert F, Barrios M. Correction of thrombocytopenia with aspirin in the primary antiphospholipid syndrome. Am J Hematol. 2001;68:215
  36. Lesprit P, Godeau B, Wechsler B. Dapsone in thrombocytopenia of the antiphospholipid antibody syndrome. Ann Intern Med. 1995;122:802
  37. Galindo M, Khamashta MA, Hughes GR. Splenectomy for refractory thrombocytopenia in the antiphospholipid syndrome. Rheumatology (Oxford). 1999;38:848–853
  38. Delgado Alves J, Inanc M, Diz-Kucukkaya R, Grima B, Soromenho F, Isenberg DA. Thrombotic risk in patients submitted to splenectomy for systemic lupus erythematosus and antiphospholipid antibody syndrome-related thrombocytopenia. Eur J Intern Med. 2004;15:162–167
  39. Hakim AJ, Machin SJ, Isenberg DA. Autoimmune thrombocytopenia in primary antiphospholipid syndrome and systemic lupus erythematosus: the response to splenectomy. Semin Arthritis Rheum. 1998;28:20–25
  40. Ikeda M, Sekimoto M, Takiguchi S, Kubota M, Ikenaga M, Yamamoto H, et al. High incidence of thrombosis of the portal venous system after laparoscopic splenectomy: a prospective study with contrast-enhanced CT scan. Ann Surg. 2005;241:208–216
  41. Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146:25–33
  42. Ames PR, Tommasino C, Fossati G, Scenna G, Brancaccio V, Ferrara F. Limited effect of rituximab on thrombocytopaenia and anticardiolipin antibodies in a patient with primary antiphospholipid syndrome. Ann Hematol. 2007;86:227–228
  43. Trappe R, Loew A, Thuss-Patience P, Dorken B, Riess H. Successful treatment of thrombocytopenia in primary antiphospholipid antibody syndrome with the anti-CD20 antibody rituximab--monitoring of antiphospholipid and anti-GP antibodies: a case report. Ann Hematol. 2006;85:134–135
  44. Ahn ER, Lander G, Bidot CJ, Jy W, Ahn YS. Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy. Am J Hematol. 2005;78:127–129
  45. Harris EN, Gharavi AE, Hegde U, Derue G, Morgan SH, Englert H, et al. Anticardiolipin antibodies in autoimmune thrombocytopenic purpura. Br J Haematol. 1985;59:231–234
  46. Stasi R, Stipa E, Masi M, Oliva F, Sciarra A, Perrotti A, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood. 1994;84:4203–4208
  47. Arfors L, Winiarski J, Lefvert AK. Prevalence of antibodies to cardiolipin in chronic ITP and reactivity with platelet membranes. Eur J Haematol. 1996;56:230–234
  48. Lipp E, von Felten A, Sax H, Muller D, Berchtold P. Antibodies against platelet glycoproteins and antiphospholipid antibodies in autoimmune thrombocytopenia. Eur J Haematol. 1998;60:283–288
  49. Diz-Kucukkaya R, Hacihanefioglu A, Yenerel M, Turgut M, Keskin H, Nalcaci M, et al. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood. 2001;98:1760–1764
  50. Bidot CJ, Jy W, Horstman LL, Ahn ER, Jimenez JJ, Yaniz M, et al. Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission. Br J Haematol. 2005;128:366–372
  51. Bidot CJ, Jy W, Horstman LL, Ahn ER, Yaniz M, Ahn YS. Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS). Am J Hematol. 2006;81:391–396
  52. Pierrot-Deseilligny C, Khellaf M, Gouault M, Intrator L, Michel M, Bierling P, et al. Prevalence and Clinical Significance of Elevated Antiphospholipid Antibodies in Adults with Immune Thrombocytopenic Purpura. Blood. 2006;108:1083
  53. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40
  54. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003;120:574–96.
  55. Bulvik S, Aronson I, Ress S, Jacobs P. Extensive bone marrow necrosis associated with antiphospholipid antibodies. Am J Med. 1995;98:572–574
  56. Paydas S, Kocak R, Zorludemir S, Baslamisli F. Bone marrow necrosis in antiphospholipid syndrome. J Clin Pathol. 1997;50:261–262
  57. Murphy PT, Sivakumaran M, Casey MC, Liddicoat A, Wood JK. Lymphoma associated bone marrow necrosis with raised anticardiolipin antibody. J Clin Pathol. 1998;51:407–409
  58. Moore J, Ma DD, Concannon A. Non-malignant bone marrow necrosis: a report of two cases. Pathology. 1998;30:318–320
  59. Schaar CG, Ronday KH, Boets EP, van der Lubbe PA, Breedveld FC. Catastrophic manifestation of the antiphospholipid syndrome. J Rheumatol. 1999;26:2261–2264
  60. Sinha J, Chowdhry I, Sedan S, Barland P. Bone marrow necrosis and refractory HELLP syndrome in a patient with catastrophic antiphospholipid antibody syndrome. J Rheumatol. 2002;29:195–197
  61. Thuerl C, Altehoefer C, Spyridonidis A, Laubenberger J. Imaging findings in the rare catastrophic variant of the primary antiphospholipid syndrome. Eur Radiol. 2002;12:545–548
  62. Spyropoulos AC. Membranous obstruction of the inferior vena cava and extensive bone marrow necrosis associated with catastrophic antiphospholipid syndrome. Journal of Clinical Rheumatology. 1999;5:279–284
  63. Dubost JJ, Kemeny JL, Soubrier M, Guelon D, Bommelaer G, Amouroux J, et al. [Primary antiphospholipid syndrome of fatal course and osteoarticular cytosteatonecrosis]. Rev Med Interne. 1994;15:535–540
  64. Vasoo S, Sangle S, Zain M, D’Cruz D, Hughes G. Orthopaedic manifestations of the antiphospholipid (Hughes) syndrome. Lupus. 2005;14:339–345
  65. Espinosa G, Bucciarelli S, Cervera R, Lozano M, Reverter JC, de la Red G, et al. Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies. Ann Rheum Dis. 2004;63:730–736
  66. Asherson RA. New subsets of the antiphospholipid syndrome in 2006: “PRE-APS” (probable APS) and microangiopathic antiphospholipid syndromes (“MAPS”). Autoimmun Rev. 2006;6:76–80
  67. Asherson RA, Pierangeli SS, Cervera R. Is there a microangiopathic antiphospholipid syndrome?. Ann Rheum Dis. 2007;66:429–432
  68. Jain R, Chartash E, Susin M, Furie R. Systemic lupus erythematosus complicated by thrombotic microangiopathy. Semin Arthritis Rheum. 1994;24:173–182
  69. Durand JM, Lefevre P, Kaplanski G, Soubeyrand J. Thrombotic microangiopathy and the antiphospholipid antibody syndrome. J Rheumatol. 1991;18:1916–1918
  70. Trent K, Neustater BR, Lottenberg R. Chronic relapsing thrombotic thrombocytopenic purpura and antiphospholipid antibodies: a report of two cases. Am J Hematol. 1997;54:155–159
  71. Uribe T, Nawata Y, Mori N. Thrombotic thrombocytoenic purpura (TTP) observed in a patient with primary antiphospholipid antibody syndrome. Ryumachi. 1994;34:981–987
  72. Musa MO, Nounou R, Sahovic E, Seth P, Qadi A, Aljurf M. Fulminant thrombotic thrombocytopenic purpura in two patients with systemic lupus erythematosus and phospholipid autoantibodies. Eur J Haematol. 2000;64:433–435
  73. Amoura Z, Costedoat-Chalumeau N, Veyradier A, Wolf M, Ghillani-Dalbin P, Cacoub P, et al. Thrombotic thrombocytopenic purpura with severe ADAMTS-13 deficiency in two patients with primary antiphospholipid syndrome. Arthritis Rheum. 2004;50:3260–3264
  74. Cerveny KC, Sawitzke AD. Relapsing catastrophic antiphospholipid antibody syndrome: a mimic for thrombotic thrombocytopenic purpura?. Lupus. 1999;8:477–481
  75. Kincaid-Smith P, Fairley KF, Kloss M. Lupus anticoagulant associated with renal thrombotic microangiopathy and pregnancy-related renal failure. Q J Med. 1988;68:795–815
  76. Kniaz D, Eisenberg GM, Elrad H, Johnson CA, Valaitis J, Bregman H. Postpartum hemolytic uremic syndrome associated with antiphospholipid antibodies. A case report and review of the literature. Am J Nephrol. 1992;12:126–133
  77. Ardiles LG, Olavarria F, Elgueta M, Moya P, Mezzano S. Anticardiolipin antibodies in classic pediatric hemolytic-uremic syndrome: a possible pathogenic role. Nephron. 1998;78:278–283
  78. Le Thi Thuong D, Tieulie N, Costedoat N, Andreu MR, Wechsler B, Vauthier-Brouzes D, et al. The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women. Ann Rheum Dis. 2005;64:273–278
  79. Ornstein MH, Rand JH. An association between refractory HELLP syndrome and antiphospholipid antibodies during pregnancy; a report of 2 cases. J Rheumatol. 1994;21:1360–1364
  80. Koenig M, Roy M, Baccot S, Cuilleron M, de Filippis JP, Cathebras P. Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome. Clin Rheumatol. 2005;24:166–168
  81. Rottem M, Krause I, Fraser A, Stojanovich L, Rovensky J, Shoenfeld Y. Autoimmune hemolytic anaemia in the antiphospholipid syndrome. Lupus. 2006;15:473–477
  82. Guzman J, Cabral AR, Cabiedes J, Pita-Ramirez L, Alarcon-Segovia D. Antiphospholipid antibodies in patients with idiopathic autoimmune haemolytic anemia. Autoimmunity. 1994;18:51–56
  83. Kokori SI, Ioannidis JP, Voulgarelis M, Tzioufas AG, Moutsopoulos HM. Autoimmune hemolytic anemia in patients with systemic lupus erythematosus. Am J Med. 2000;108:198–204
  84. Pullarkat V, Ngo M, Iqbal S, Espina B, Liebman HA. Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism. Br J Haematol. 2002;118:1166–1169
  85. Sthoeger Z, Sthoeger D, Green L, Geltner D. The role of anticardiolipin autoantibodies in the pathogenesis of autoimmune hemolytic anemia in systemic lupus erythematosus. J Rheumatol. 1993;20:2058–2061

PII: S0268-960X(08)00024-6

doi: 10.1016/j.blre.2008.03.005

Blood Reviews
Volume 22, Issue 4 , Pages 187-194 , July 2008

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