Microthrombotic/Microangiopathic Manifestations of the Antiphospholipid Syndrome

  • Sonja Praprotnik
  • Dušan Ferluga
  • Alenka Vizjak
  • Anastazija Hvala
  • Tadej Avčin
  • Blaž Rozman
Article

Abstract

The paper presents an overview of clinical manifestations and histopathologic findings in different organs in microvascular thrombotic and microangiopathic antiphospholipid syndrome (MAPS). Subsets of antiphospholipid syndrome (APS) are presented and defined. Clinico-pathologic correlations seem insufficient so far, because of a lack of detailed systematic studies of the histopathology in different organs. Based on their own autopsy and biopsy studies, the authors propose a novel categorization of histopathologic lesions that occur in patients with classic and catastrophic APS. In addition to the already accepted category of a microvascular thrombotic type of lesions, microangiopathic lesions consistent with thrombotic microangiopathy are proposed to be included in new revised classification criteria for definite APS. Microvascular thrombotic and so far underestimated microangiopathic histopathologic lesions have been shown to appear in various combinations and of different ages in patients with both classic and catastrophic APS, which fits into the concept of MAPS. These preliminary findings of our studies are also in line with the most recent hypothesis of two main mechanisms in the pathogenesis of APS, emphasizing a key role of endothelial cell affection induced by aPL on the one hand and interference with coagulation cascade on the other side.

Keywords

Antiphospholipid syndrome Microvascular thrombotic/microangiopathic antiphospholipid syndrome Clinical manifestations Diagnostic criteria Thrombotic microangiopathy Histopathology 

Notes

Acknowledgments

We are grateful to Mrs. Tatjana Kobenter, BSc, Metka Janc, Andreja Drofenik, Nataša Štok-Pfajfer, and Branka Grmek, as well as Mr. Žiga Kušar, BSc for their technical assistance.

References

  1. 1.
    Hughes G, Harris EN, Gharavi A (1986) The anticardiolipin syndrome. J Rheumatol 13:486–489PubMedGoogle Scholar
  2. 2.
    Shoenfeld Y (2003) Systemic antiphospholipid syndrome. Lupus 12:497–849PubMedCrossRefGoogle Scholar
  3. 3.
    Asherson RA (1992) The catastrophic antiphospholipid syndrome. J Rheumatol 19:508–512PubMedGoogle Scholar
  4. 4.
    Lie JT (1997) Prevalence and pathology of vascular occlusive disease in the antiphospholipid syndrome. Cardiovasc Pathol 6:185–195CrossRefGoogle Scholar
  5. 5.
    Asherson RA, Cervera R, Piette JC et al (1998) Catastrophic antiphospholipid syndrome. Clinical and laboratory features in 50 patients. Medicine 80:195–207CrossRefGoogle Scholar
  6. 6.
    Wilson WA, Gharavi AE, Koike T et al (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis Rheum 42:1309–1311PubMedCrossRefGoogle Scholar
  7. 7.
    Levine JS, Branch DW, Rauch J (2002) The antiphospholipid syndrome. NEJM 346:752–763PubMedCrossRefGoogle Scholar
  8. 8.
    Baker WF, Bick RL (2008) The clinical spectrum of antiphospholipid syndrome. Hematol Oncol Clin North Am 22:33–52PubMedCrossRefGoogle Scholar
  9. 9.
    Montero PJ, Franco V, Strauss Y, La Pena A (2008) The antiphospholipid syndrome. Medicrit 5:27–40Google Scholar
  10. 10.
    Vora SK, Asherson RA, Erkan D (2006) Catastrophic antiphospholipid syndrome. J Intens Care Med 21:144–159CrossRefGoogle Scholar
  11. 11.
    Miyakis S, Lochshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306PubMedCrossRefGoogle Scholar
  12. 12.
    Asherson RA (2006) New subsets of the antiphospholipid syndrome in 2006: “PRE-APS” (probable APS) and microangiopathic antiphospholipid syndrome (“MAPS”). Autoimmun Rev 6:76–80PubMedCrossRefGoogle Scholar
  13. 13.
    Asherson RA, Cervera R (2008) Microvascular and microangiopathic antiphospholipid associated syndromes (“MAPS”): Semantic or antisemantic. Autoimmun Rev 7:164–167PubMedCrossRefGoogle Scholar
  14. 14.
    Espinosa G, Buciarelli S, Cervera R (2004) Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies. Ann Rheum Dis 63:730–736PubMedCrossRefGoogle Scholar
  15. 15.
    Reyes E, Alarcon-Segovia D (2002) Pathology of the antiphospholipid syndrome. In: Asherson RA et al (ed) The Antiphospholipid Syndrome II: Autoimmune Thrombosis. Elsevier, Amsterdam, pp 131–136Google Scholar
  16. 16.
    Cervera R, Piette JC, Font J et al (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 46:1019–1027PubMedCrossRefGoogle Scholar
  17. 17.
    Nahass GT (1997) Antiphospholipid antibodies and the antiphospholipid antibodies syndrome. J Am Acad Dematol 36:149–168CrossRefGoogle Scholar
  18. 18.
    Alegre VA, Winkelmann RK (1988) Histopathologic and immunofluorescence study of skin lesions associated with circulating anticoagulant. J Am Acad Dermatol 19:117–124PubMedCrossRefGoogle Scholar
  19. 19.
    Smith KJ, Skelton HG, James WD et al (1990) Cutaneous histopathologic findings in “antiphospholipid syndrome”. Arch Dermatol 126:1176–1183PubMedCrossRefGoogle Scholar
  20. 20.
    Stephansson EA, Niemi KM, Jouhikainen T et al (1991) Lupus anticoagulant and the skin. A long term follow-up of SLE patients with special reference to histopathologic findings. Acta Derm Venereol 71:416–422PubMedGoogle Scholar
  21. 21.
    Grob JJ, Bonerandi JJ (1986) Cutaneous manifestations associated with the presence of the lupus anticoagulant: a report of two cases and the review of the literature. J Am Acad Dermatol 15:211–219PubMedCrossRefGoogle Scholar
  22. 22.
    Selva A, Ordi J, Roca M et al (1994) Pyoderma gangrenosum-like ulcers associated with lupus anticoagulant. Dermatology 189:182–184PubMedCrossRefGoogle Scholar
  23. 23.
    Hughson MD, McCarty GA, Brumback RA (1995) Spectrum of vascular pathology affecting patients with the antiphospholipid syndrome. Hum Pathol 26:716–724PubMedCrossRefGoogle Scholar
  24. 24.
    Lie JT (1994) Vasculitis in the antiphospholipid syndrome: culpit or consort. J Rheumatol 21:397–399PubMedGoogle Scholar
  25. 25.
    Mujic F, Lloyd M, Cuadrado MJ et al (1995) Prevalence and clinical significance of subungual splinter hemorrhages in patients with the antiphospholipid syndrome. Clin Exp Rheumatol 13:327–331PubMedGoogle Scholar
  26. 26.
    Ornstein MH, Rand JH (1994) An association between refractory HELLP syndrome and antiphospholipid antibodies during pregnancy; a report of 2 cases. J Rheumatol 21:1360–1364PubMedGoogle Scholar
  27. 27.
    Frances C, Piette CP (2002) Dermatologic manifestations in the antiphospholipid syndrome. In: Asherson RA et al (ed) The Antiphospholipid Syndrome II: Autoimmune Thrombosis. Elsevier, Amsterdam, pp 235–244Google Scholar
  28. 28.
    Frances C, Piette JC, Asherson RA (2006) Dermatologic aspects of antiphospholipid antibody syndrome. In: Sarzi-Puttini P et al (eds) Handbook of Systemic Autoimmune Diseases. Elsevier 5:103–117Google Scholar
  29. 29.
    Frances C, Niang S, Laffitte E et al (2005) Dermatologic manifestations of the antiphospholipid syndrome: two hundred consecutive cases. Arthritis Rheum 52:1785–1793PubMedCrossRefGoogle Scholar
  30. 30.
    Šipek-Dolničar A, Hojnik M, Božič B et al (2002) Clinical presentations and vascular histopathology in autopsied patients with systemic lupus erythematosus and anticardiolipin antibodies. Clin Exp Rheumatol 20:335–342PubMedGoogle Scholar
  31. 31.
    Creamer D, Black MM, Calonje E (2000) Reactive angioendotheliomatosis in association with the antiphospholipid syndrome. J Am Acad Dermatol 42:903–906PubMedCrossRefGoogle Scholar
  32. 32.
    Thai KE, Barrett W, Kossard S (2003) Reactive angioendotheliomathosis in the setting of antiphospholipid syndrome. Australas J Dermatol 14:99–106Google Scholar
  33. 33.
    Sharkey MP, Daryanani II, Gillett MB, Jones SK (2002) Localized cutaneous necrosis associated with the antiphospholipid syndrome. Australas J Dermatol 43:218–220PubMedCrossRefGoogle Scholar
  34. 34.
    Tomb R, Maalouf E, Attoui S (2008) Cutaneous nodular lesions and antiphospholipid syndrome. Ann Dermatol Venereol 135:484–487PubMedCrossRefGoogle Scholar
  35. 35.
    Bucciarelli S, Cervera R, Espinosa G et al (2006) Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors. Autoimmun Rev 6:72–75PubMedCrossRefGoogle Scholar
  36. 36.
    Maggiorini M, Knoblauch A, Schneider J, Russi EW (1997) Diffuse microvascular pulmonary thrombosis associated with primary antiphospholipid antibody syndrome. Eur Respir J 10:727–730PubMedGoogle Scholar
  37. 37.
    Kerr JE, Poe J, Kramer Z (1997) Antiphospholipid antibody syndrome presenting as a refractory noninflammatory pulmonary vasculopathy. Chest 112:1707–1710PubMedCrossRefGoogle Scholar
  38. 38.
    Deane KD, West SG (2005) Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. Semin Arthritis Rheum 35:154–165PubMedCrossRefGoogle Scholar
  39. 39.
    Espinosa G, Cervera R, Garcia-Carrasco et al (2002) Pulmonary involvement in the antiphospholipid syndrome. In: Wells AU, Denton CP (eds) Handbook of Systemic Autoimmune Disease. Amsterdam, Elsevier 2:137–145Google Scholar
  40. 40.
    Šipek-Dolničar A, Hojnik M, Rozman B et al (2000) Small vessel thrombosis without major thrombotic events in systemic lupus erythematosus patients with antiphospholipid syndrome. Wien Klin Wochenschr 112:707–710PubMedGoogle Scholar
  41. 41.
    Long BR, Leya F (2008) The role of antiphospholipid syndrome in cardiovascular disease. Hematol Oncol Clin North Am 22:79–94PubMedCrossRefGoogle Scholar
  42. 42.
    Leung WH, Wong KL, Lau et al (1990) Association between antiphospholipid antibodies and cardiac abnormalities in patients with systemic lupus erythematosus. Am J Med 89:411–419Google Scholar
  43. 43.
    Murphy J, Leach IH (1989) Findings at necropsy in the heart of a patient with anticardiolipin syndrome. Br Heart J 62:61–64PubMedCrossRefGoogle Scholar
  44. 44.
    Brown JH, Doherty CC, Allen DC et al (1988) Fatal cardiac failure due to myocardial microthrombi in systemic lupus erythematosus. Br Med J (Clin Res Ed) 296:1505CrossRefGoogle Scholar
  45. 45.
    Kaplan SD, Chartash EK, Pizzarello RA et al (1992) Cardiac manifestations of the antiphospholipid syndrome. Am Heart J 124:1331–1338PubMedCrossRefGoogle Scholar
  46. 46.
    Von Landenberg P, Asherson RA, Piette JC (2002) Renal, hepatic and other intraabdominal manifestations in the antiphospholipid syndrome. In: Asherson et al (ed) The Antiphospholipid Syndrome II: Autoimmune Thrombosis. Elsevier, Amsterdam, pp 189–204Google Scholar
  47. 47.
    Uthman I, Khamashta M (2007) The abdominal manifestation of the antiphospholipid syndrome. Rhematol 46:1641–1647CrossRefGoogle Scholar
  48. 48.
    Nakamura H, Uchara H, Okada T (1989) Occlusion of small hepatic veins associated with systemic lupus erythematosus with the lupus anticoagulant and anti-cardiolipin antibody. Hepatogastroenterol 36:393–397Google Scholar
  49. 49.
    Barak N, Orion Y, Schneider M et al (1999) Case report: hepatic involvement in antiphospholipid syndrome. J Gastroenterol Hepatol 14:1124–1128PubMedCrossRefGoogle Scholar
  50. 50.
    Kalman DR, Khan A, Romain PL, Nompleggi DJ (1996) Giant gastric ulceration associated with antiphospholipid antibody syndrome. Am J Gastroenterol 91:1244–1247PubMedGoogle Scholar
  51. 51.
    Briley DP, Coull BM, Goodnight SH (1989) Neurological disease associated with antiphospholipid syndrome. Ann Neurol 25:221–227PubMedCrossRefGoogle Scholar
  52. 52.
    Asherson RA, Cervera R (2003) The antiphospholipid syndrome: multiple faces beyond the classical presentation. Autoimmun Rev 2:140–151PubMedCrossRefGoogle Scholar
  53. 53.
    Cuadrado MJ, Khamashta MA, Ballesteros A et al (2000) Can neurologic manifestations of Hughes (antiphospholipid) syndrome be distinguished from multiple sclerosis? Analysis of 27 patients and review of the literature. Medicine 79:57–68PubMedCrossRefGoogle Scholar
  54. 54.
    Tektonidou MG, Grigorios Kotoulas NV, Antoniou A, Moutsopoulos HM (2006) Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med 166:2278–2284PubMedCrossRefGoogle Scholar
  55. 55.
    Brey RL, Levine SR, Stallworth CL (2002) Neurologic manifestations in the antiphospholipid syndrome. In: Asherson RA et al (ed) The Antiphospholipid Syndrome II: Autoimmune Thrombosis. Elsevier, Amsterdam, pp 155–168Google Scholar
  56. 56.
    Shoenfeld Y, Nahum A, Korczyn AD et al (2003) Neuronal-binding antibodies from patients with antiphospholipid syndrome induce cognitive deficits following intrathecal passive transfer. Lupus 12:436–442PubMedCrossRefGoogle Scholar
  57. 57.
    Hugson MD, McCarty GA, Sholer CM, Brumback RA (1993) Thrombotic cerebral arteriopathy in patients with the antiphospholipid syndrome. Mod Pathol 6:644–653Google Scholar
  58. 58.
    Miesbach W, Gilzinger A, Gokpinar B et al (2006) Prevalence of antiphospholipid antibodies in patients with neurological symptoms. Clin Neurol Neurosur 108:135–142CrossRefGoogle Scholar
  59. 59.
    Durrani OM, Gordon C, Murray PI (2002) Primary anti-phospholipid antibody syndrome (APS). Surv Ophthalmol 4:215–238CrossRefGoogle Scholar
  60. 60.
    Asherson RA, Merry P, Acheson JF et al (1989) Antiphospholipid antibodies: a risk factor for occlusive ocular vascular disease in systemic lupus erythematosus and the primary antiphospholipid syndrome. Ann Rheum Dis 48:358–361PubMedCrossRefGoogle Scholar
  61. 61.
    Castanon C, Amigo MC, Banales JL et al (1995) Ocular vaso-occlusive disease in primary antiphospholipid syndrome. Ophthalmology 102:256–262PubMedGoogle Scholar
  62. 62.
    Giorgi D, Pace F, Giorgi A et al (1999) Retinopathy in systemic lupus erythematosus: pathogenesis and approach to therapy. Hum Immunol 60:688–696PubMedCrossRefGoogle Scholar
  63. 63.
    Falcini F, Taccetti G, Ermini M et al (1997) Catastrophic antiphospholipid antibody syndrome in pediatric systemic lupus erythematosus. J Rheumatol 24:389–392PubMedGoogle Scholar
  64. 64.
    Asherson RA, Cervera R, Piette JC et al (2001) Catastrophic antiphospholipid syndrome. Clues to the pathogenesis from a series of 80 patients. Medicine 80:355–377PubMedCrossRefGoogle Scholar
  65. 65.
    Tsirpanlis G, Moustakas G, Sakka E et al (2005) Catastrophic antiphospholipid syndrome in a 14-year-old child. Pediatr Nephrol 20:519–521PubMedCrossRefGoogle Scholar
  66. 66.
    Avčin T, Cimaz R, Silverman ED et al (2008) Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics 122:1100–1107CrossRefGoogle Scholar
  67. 67.
    Orsino A, Schneider R, DeVeber G et al (2004) Childhood acute myelomonocytic leukemia (AML-M4) presenting as catastrophic antiphospholipid antibody syndrome. J Pediatr Hematol Oncol 26:327–330PubMedCrossRefGoogle Scholar
  68. 68.
    Sharma J, Karthik S, Rao S et al (2005) Catastrophic antiphospholipid antibody syndrome. Pediatr Nephrol 20:998–999PubMedCrossRefGoogle Scholar
  69. 69.
    Park JM, Shin JI, Shin YH et al (2007) Catastrophic antiphospholipid syndrome in a 7-year-old girl. Clin Rheumatol 26:1011–1013PubMedCrossRefGoogle Scholar
  70. 70.
    Iman S, Sidki K, al-Marshedy AR, Judzewitsch R (1991) Addison’s disease, hypertension, renal and hepatic microthrombosis in ‘primary’ antiphospholipid syndrome. Postgrad Med J 67:385–388CrossRefGoogle Scholar
  71. 71.
    De-Leon-Bojorge B, Zaltzman-Girsevich S, Ortega-Salgado A et al (2006) Thrombotic microangiopathy involving the gallbladder as an unusual manifestation of systemic lupus erythematosus and antiphospholipid syndrome: case report and review of the literature. World J Gastroenterol 12:7206–7209PubMedGoogle Scholar
  72. 72.
    Do Sameiro Faria M, Mota C, Barlot J et al (2000) Hemolytic uremic syndrome cardiomyopathy, cutaneous vasculopathy and antiphospholipid activity. Nephrol Dial Transplant 15:1891–1892PubMedCrossRefGoogle Scholar
  73. 73.
    Meglič A, Grosek Š, Benedik-Dolničar M, Avčin T (2008) Atypical haemolytic uremic syndrome complicated by microangiopathic antiphospholipid-associated syndrome. Lupus 17:842–845PubMedCrossRefGoogle Scholar
  74. 74.
    Symmers WSC (1952) Thrombotic microangiopathic haemolitic anemia (thrombotic microangiopathy). Br Med J 2:897–903PubMedGoogle Scholar
  75. 75.
    Thoenes W, John HD (1980) Endotheliotropic (hemolytic) nephroangiopathy and its various manifestation forms (thrombotic microangiopathy, primary malignant nephrosclerosis, hemolytic–uremic syndrome). Klin Wochenschr 58:173–184PubMedCrossRefGoogle Scholar
  76. 76.
    Asherson RA, Cervera R, Merrill JT (2006) Thrombotic microangiopathic antiphospholipid syndromes: a continuum of conditions. Future Rheumatol 1:355–364CrossRefGoogle Scholar
  77. 77.
    Asherson RA, Pierangeli S, Cervera R (2007) Is there a microangiopathic antiphospholipid syndrome. Ann Rheum Dis 66:429–432PubMedCrossRefGoogle Scholar
  78. 78.
    Vega-Ostertag ME, Pierangeli SS (2007) Mechanisms of aPL-mediated thrombosis: effects of aPL on endothelium and platelets. Curr Rheumatol Rep 9:190–197PubMedCrossRefGoogle Scholar
  79. 79.
    O’Neil KM (2007) Role of complement in antiphospholipid syndrome. Curr Rheumatol Rep 9:205–211PubMedCrossRefGoogle Scholar
  80. 80.
    Mackworth-Young CG (2004) Antiphospholipid syndrome: multiple mechanisms. Clin Exp Immunol 136:393–401PubMedCrossRefGoogle Scholar
  81. 81.
    D’Agati V, Kunis C, Williams G, Appel GB (1990) Anti-cardiolipin antibody and renal disease: a report of three cases. J Am Soc Nephrol 1:777–784PubMedGoogle Scholar
  82. 82.
    Nochy D, Daugas E, Droz D et al (1999) The intrarenal vascular lesions associated with primary antiphospholipid syndrome. J Am Soc Nephrol 10:507–518PubMedGoogle Scholar
  83. 83.
    Amigo MC, Garcia-Torres R (2000) Kidney disease in antiphospholipid syndrome. In: Khamashta MA (ed) Hughes Syndrome. Antiphopholipid Syndrome. Springer, Berlin, pp 71–81Google Scholar
  84. 84.
    Seshan SV (2000) Vascular complications in lupus nephritis and lupus-like syndromes. Wien Klin Wochenschr 112:687–691PubMedGoogle Scholar
  85. 85.
    Daugas E, Nochy D, Le Thi Huong D et al (2002) Antiphospholipid syndrome nephropathy in systemic lupus erythematosus. J Am Soc Nephrol 13:42–52PubMedCrossRefGoogle Scholar
  86. 86.
    Amigo MC (2006) Kidney disease in antiphospholipid syndrome. Rheum Dis Clin North Am 32:509–522PubMedCrossRefGoogle Scholar
  87. 87.
    Hill GS, Nochy D (2007) Antiphospholipid syndrome in systemic lupus erythematosus. J Am Soc Nephrol 18:2461–2464PubMedCrossRefGoogle Scholar
  88. 88.
    Jara LJ, Medina G, Vera-Lastra O (2007) Systemic antiphospholipid syndrome and atherosclerosis. Clin Rev Allerg Immunol 32:172–177CrossRefGoogle Scholar
  89. 89.
    Moroni G, Ventura D, Riva P et al (2004) Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis. Am J Kidney Dis 43:28–36PubMedCrossRefGoogle Scholar
  90. 90.
    Fakhouri F, Noël LH, Zuber J et al (2003) The expanding spectrum of renal diseases associated with antiphospholipid syndrome. Am J Kidney Dis 41:1205–1211PubMedCrossRefGoogle Scholar
  91. 91.
    Asherson RA, Espinosa G, Cervera R et al (2005) Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients. Ann Rheum Dis 64:943–946PubMedCrossRefGoogle Scholar
  92. 92.
    Voung PN, Berry SC (2002) The Pathology of Vessels. Springer, Berlin, pp 35–67Google Scholar
  93. 93.
    Bontas E, Tanikawa A, Bartos D et al (2006) Polymorphism of skin involvement in Hughes (antiphospholipid) syndrome. J Thromb Haemost 4:295–306CrossRefGoogle Scholar
  94. 94.
    Rollino C, Mazzucco G, Boero R (2003) Is it possible to diagnose primary anti-phospholipid syndrome (PAPS) on the basis of renal thrombotic microangiopathy (PAPS nephropathy) in the absence of other thrombotic process. Renal Failure 25:1043–1049PubMedCrossRefGoogle Scholar
  95. 95.
    Saracino A, Ramuni A, Pannarale G, Coratelli P (2005) Kidney disease associated with primary antiphospholipid syndrome: clinical signs and histopathologic features in an case experience of five cases. Clin Nephrol 63:471–476PubMedGoogle Scholar
  96. 96.
    Griffiths MH, Papadaki L, Neild GH (2000) The renal pathology of primary antiphospholipid syndrome: a distinctive form of endothelial injury. Q J Med 93:457–467Google Scholar
  97. 97.
    Tektonidou MG, Sotsiou F, Nakopoulou L et al (2004) Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies. Arthritis Rheum 50:2569–2579PubMedCrossRefGoogle Scholar
  98. 98.
    Asherson RA, Cervera R, Shepshelovich D, Shoenfeld Y (2006) Nonthrombotic manifestations of the antiphospholipid syndrome: away from thrombosis. J Rheumatol 33:1038–1344PubMedGoogle Scholar
  99. 99.
    Pilling J, Cutaia M (1997) The antiphospholipid antibody syndrome: a vascular disease with pulmonary manifestations. Chest 112:1451–1453PubMedCrossRefGoogle Scholar
  100. 100.
    Johnson CM, Mureebe L, Silver D (2005) Hypercoagulable states: a review. Vasc Endovasc Surg 39:123–133CrossRefGoogle Scholar
  101. 101.
    Moake JL (2002) Thrombotic microangiopathies. N Engl J Med 347:589–600PubMedCrossRefGoogle Scholar
  102. 102.
    Matsuura E, Kobayashi K, Lopez LR (2008) Preventing autoimmune and infection triggered atherosclerosis for an enduring healthful lifestyle. Autoimmun Rev 7:214–222PubMedCrossRefGoogle Scholar
  103. 103.
    Yang YH, Chuang YH, Wang LC et al (2008) The immunobiology of Henoch–Schonlein purpura. Autoimmun Rev 7:179–184PubMedCrossRefGoogle Scholar
  104. 104.
    Kallenberg CG (2008) Pathogenesis of PR3-ANCA associated vasculitis. J Autoimmun 30:29–36PubMedCrossRefGoogle Scholar
  105. 105.
    Belizna CC, Richard V, Thuillez C et al (2007) Insights into atherosclerosis therapy in antiphospholipid syndrome. Autoimmun Rev 7:46–51PubMedCrossRefGoogle Scholar
  106. 106.
    Rav-Acha M, Plot L, Peled N, Amital H (2007) Coronary involvement in Takayasu’s arteritis. Autoimmun Rev 6:566–71PubMedCrossRefGoogle Scholar
  107. 107.
    Alard JE, Dueymes M, Youinou P, Jamin C (2007) Modulation of endothelial cell damages by anti-Hsp60 autoantibodies in systemic autoimmune diseases. Autoimmun Rev 6:438–43PubMedCrossRefGoogle Scholar
  108. 108.
    Hahn BH, Grossman J, Chen W, McMahon M (2007) The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia. J Autoimmun 28:69–75PubMedCrossRefGoogle Scholar
  109. 109.
    Ilaria C, Nebuloni M, Cetin I et al (2007) J Autoimmun 28:160–164CrossRefGoogle Scholar
  110. 110.
    Koike T, Bohgaki M, Amengual O, Atsumi T (2007) Antiphospholipid antibodies: lessons from the bench. J Autoimmun 28:129–33PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Sonja Praprotnik
    • 1
  • Dušan Ferluga
    • 2
  • Alenka Vizjak
    • 2
  • Anastazija Hvala
    • 2
  • Tadej Avčin
    • 3
  • Blaž Rozman
    • 1
  1. 1.Clinical Department of RheumatologyUniversity Medical Center LjubljanaLjubljanaSlovenia
  2. 2.Institute of Pathology, Faculty of Medicine University of LjubljanaLjubljanaSlovenia
  3. 3.Department of Allergology, Rheumatology and Clinical ImmunologyUniversity Children’s Hospital, University Medical Center LjubljanaLjubljanaSlovenia

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