Malignancies and Catastrophic Anti-phospholipid Syndrome

  • Wolfgang MiesbachEmail author


The catastrophic anti-phospholipid (Asherson’s) syndrome (CAPS) is characterised by the rapid chronological development of fulminant thrombotic complications that predominantly affect small vessels and differs from the anti-phospholipid syndrome in its accelerated systemic involvement leading to multi-organic failure. Malignancy may play a pathogenic role in patients with CAPS, whereas infections are more important as triggering factors in patients without malignancies. CAPS patients with malignancies are generally older than CAPS patients without malignancies; they generally have the worst prognosis of the entire CAPS cohort.


Malignancy Thrombosis Catastrophic anti-phospholipid syndrome CAPS Asherson’s syndrome Anti-phospholipid syndrome 


  1. 1.
    Trousseau A. Phlegmasia alba dolens. In: Clinique Medical de L’Hotel Dieu de Paris Vol 3 London. The New Sydenham Society 1865:94Google Scholar
  2. 2.
    Heit JA, Silverstein MD, Mohr DN et al (2000) Risk factors for deep vein thrombosis and pulmonary embolism: a population-based control study. Arch Intern Med 160:809–815PubMedCrossRefGoogle Scholar
  3. 3.
    Lee AY, Levine MN (1999) The thrombophilic state induced by therapeutic agents in the cancer patient. Semin Thromb Haemost 25:137–145CrossRefGoogle Scholar
  4. 4.
    Blom JW, Doggen CJ, Osanto S (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293:715–722PubMedCrossRefGoogle Scholar
  5. 5.
    Prandoni P, Falanga A, Piccioli A (2005) Cancer and venous thromboembolism. Lancet Oncology 6:401–410PubMedCrossRefGoogle Scholar
  6. 6.
    Schulman S, Lindmarker P (2000) Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of anticoagulation. Trial. N Engl J Med 342:1953–1958PubMedCrossRefGoogle Scholar
  7. 7.
    Monreal M, Fernandez-Llamazares J, Perandreu J et al (1997) Occult cancer in patients with venous thromboembolism: which patients, which cancers. Thromb Haemost 78:1316–1318PubMedGoogle Scholar
  8. 8.
    Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 4:295–306PubMedCrossRefGoogle Scholar
  9. 9.
    Asherson RA (2000) Antiphospholipid antibodies, malignancies and paraproteinemias. J Autoimmun 15:117–122PubMedCrossRefGoogle Scholar
  10. 10.
    Asherson RA, Cervera R (2000) Antiphospholipid antibodies and malignancies. In: Shoenfeld Y (ed) Cancer and autoimmunity. Elsevier, Amsterdam, pp 93–102CrossRefGoogle Scholar
  11. 11.
    Kazmierczak M, Lewandowski K, Wojtukiewicz MZ (2005) Cancer proagulant in patients with adenocarcinomas. Blood Coagul Fibrinolysis 16:543–537PubMedCrossRefGoogle Scholar
  12. 12.
    Langer F, Eifrig B, Hegewich-Becker S (2002) Complicated antiphospholipid syndrome. Dtsch Med Wochenschrift 127:1458–1462CrossRefGoogle Scholar
  13. 13.
    Schreiber DP, Kepp DS (1986) Axillary subclavian vein thrombosis following combination chemotherapy and radiation therapy in lymphoma. Int H Radiat Oncol Biol Phys 12:391–395Google Scholar
  14. 14.
    Ruffatti A, Avorsa A, Del Ross T et al (1994) Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome. J Rheumatol 21:2162–2163PubMedGoogle Scholar
  15. 15.
    Kozlowski CL, Johnson MJ, Gorst DW et al (1987) Lung cancer, immune thrombocytopenia and the lupus inhibitor. Postgrad Med 63:793–795CrossRefGoogle Scholar
  16. 16.
    Papagiannis A, Cooper A, Bans J (1994) Pulmonary embolism and lupus anticoagulant in a woman with renal cell carcinoma. J Urol 152:941–942PubMedGoogle Scholar
  17. 17.
    Park CJ, Gho HI, Kim SI (1991) A study of changes of coagulation inhibitors and fibrinolysis inhibitors in patients with liver cirrhosis and hepatoma. J Korean Med Sol 6:1–6Google Scholar
  18. 18.
    Asherson RA, D’Cruz D (2007) Vascular occlusions in a patient with low positive antiphospholipid antibodies and subsequent development of breast carcinoma: a diagnostic dilemma. Clin Rheumatol 26:1531–1533PubMedCrossRefGoogle Scholar
  19. 19.
    Stasi R, Stipa E, Masi M, Oliva F, Sciarra A, Perrotti A, Zaccari G, Papa G (1993) Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin’s lymphoma. Thromb Haemost 70:568–572PubMedGoogle Scholar
  20. 20.
    Athale UH, Chan AK (2003) Thrombosis in children with lymphoblastic leukemia Part III. Pathogenesis of thrombosis in children with acute lymphoblastic leukemia: effects of host environment. Thromb Res 111:321–327PubMedCrossRefGoogle Scholar
  21. 21.
    Mouas H, Lortholary O, Eclache V et al (1994) Antiphospholipid syndrome during acute monocytic leukemia. Eur J Haematol 53:59–60PubMedCrossRefGoogle Scholar
  22. 22.
    Orsino A, Schneider R, DeVeber G et al (2004) Childhood acute myelomonocytic leukemia (AML-M4) presenting as catastrophic antiphospholipid syndrome. J Pedriatr Hematol Oncol 26:327–330CrossRefGoogle Scholar
  23. 23.
    Zuckerman E, Toubi E, Golan T et al (1995) Increased thromboembolic incidence in anticardiolipin-positive patients with malignancy. Br J Cancer 72:447–451PubMedGoogle Scholar
  24. 24.
    Pusterla S, Previtali S, Marziali S et al (2004) Antiphospholipid antibodies in lymphoma: prevalence and clinical significance. Hematol J 5:341–346PubMedCrossRefGoogle Scholar
  25. 25.
    Genvresse I, Lüftner D, Späth-Schwalbe E, Buttgereit F (2002) Prevelance and clinical significance of anticardiolipin and anti-ß2-glycoprotein-I antibodies in patients with non-Hodgkin’s lymphoma. Eur J Haematol 68:84–90PubMedCrossRefGoogle Scholar
  26. 26.
    Yoon KH, Wong A, Shakespeare T, Sivalingham P (2003) High prevalence of the antiphospholipid antibodies in Asian cancer patients with thrombosis. Lupus 12:112–116PubMedCrossRefGoogle Scholar
  27. 27.
    Gomez-Puerta JA, Cervera R, Espinosa G et al (2006) Antiphospholipid antibodies associated with malignancies: clinical and pathological characteristics of 120 patients. Semin Arthritis Rheum 35:322–332PubMedCrossRefGoogle Scholar
  28. 28.
    Miesbach W, Scharrer I, Asherson RA (2006) Thrombotic manifestations of the antiphospholipid syndrome in patients with malignancies. Clin Rheumatol 25:1–5CrossRefGoogle Scholar
  29. 29.
    Miesbach W, Scharrer I, Asherson RA (2007) High titres of IgM-antiphospholipid antibodies are unrelated to pathogenicity in patients with non-Hodgkin's lymphoma. Clin Rheumatol 26:95–97PubMedCrossRefGoogle Scholar
  30. 30.
    Schved JF, Dupuy-Fons C, Biron C et al (1994) A prospective epdimiological study of the occurrence of antiphospholipid antibody; the Montpelier Antiphospholipid (MAP) Study. Haemostasis 24:175–182PubMedGoogle Scholar
  31. 31.
    Piette J-C, Cervera R, Levy RA, Nasonov EL, Triplett DA, Shoenfeld Y (2000) The catastrophic antiphospholipid syndrome—Asherson’s syndrome. Ann Med Interne 154:195–196Google Scholar
  32. 32.
    Shoenfeld Y, Cervera R (2008) Asherson’s syndrome of the catastrophic antiphospholipid antibodies. J Rheumatol 35(10):2066–2068, OctPubMedGoogle Scholar
  33. 33.
    Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa M-C, Piett JC (2003) Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 12:530–534PubMedCrossRefGoogle Scholar
  34. 34.
    Cervera R, Gómez-Puerta JA, Espinosa G, Font J, De la Red G, Gil V, Bucciarelli S et al (2003) “CAPS Registry”. A review of 200 cases from the international registry of patients with catastrophic antiphospholipid syndrome (CAPS) Ann Rheum Dis OP0075Google Scholar
  35. 35.
    Asherson RA (1992) The catastrophic antiphospholipid syndrome. J Rheumatol 19(4):508–512PubMedGoogle Scholar
  36. 36.
    Bucciarelli S, Espinosa G, Cervera R et al (2006) Mortality in the catastrophic antiphospholipid syndrome. Arth Rheum 54:2568–2576CrossRefGoogle Scholar
  37. 37.
    Asherson RA (2005) Multiorgan failure and antiphospholipid antibodies: the catastrophic antiphospholipid (Asherson’s) syndrome. Immunobiology 210:727–733PubMedCrossRefGoogle Scholar
  38. 38.
    Miesbach W, Asherson RA, Cervera R, Shoenfeld Y, Gomez Puerta J, Espinosa G, Bucciarelli S (2007) Members of the CAPS Registry Group. The role of malignancies in patients with catastrophic anti-phospholipid (Asherson’s) syndrome. Clin Rheumatol 26(12):2109–2114, DecPubMedCrossRefGoogle Scholar
  39. 39.
    Cervera R, Asherson RA, Acevedo ML, Gómez-Puerta JA, Espinosa G, De La Red G, Gil V, Ramos-Casals M, Garcia-Carrasco M, Ingelmo M, Fontr J (2004) Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients. Ann Rheum Dis 63(10):1312–1317PubMedCrossRefGoogle Scholar
  40. 40.
    Cervera R, Gómez-Puerta JA, Espinosa G, Font J, De La Red G, Gil V, Bucciarelli S et al (2003) “CAPS registry”. A review of 200 cases from the international registry of patients with catastrophic antiphospholipid syndrome (CAPS). Ann Rheum Dis 62(Suppl 1):88Google Scholar
  41. 41.
    Amital H, Levy Y, Davidson C, Lundberg I, Harju A, Kosach Y, Asherson RA, Shoenfeld Y (2001) Catastrophic antiphospholipid syndrome: remission following leg amputation in 2 cases. Semin Arthritis Rheum 31(2):127–132PubMedCrossRefGoogle Scholar
  42. 42.
    Asherson RA, Davidge-Pitts MC, Wypkema E (2006) “Primary” antiphospholipid syndrome evolving into Waldenstrom’s macroglobulinaemia: a case report. Clin Rheumatol 26(2):278–280PubMedCrossRefGoogle Scholar
  43. 43.
    Asherson RA, Frances C, Iaccarino L, Khamashta MA, Malacarne F, Piette JC, Tincani A, Doria A (2006) The antiphospholipid antibody syndrome: diagnosis, skin. Clin Exp Rheumatol 24(1 Suppl 40):S46–S51PubMedGoogle Scholar
  44. 44.
    Pusterla S, Previtali S, Marziali S et al (2004) Antiphospholipid antibodies in lymphoma: prevalence and clinical significance. Hematol J 5(4):341–346PubMedCrossRefGoogle Scholar
  45. 45.
    Genvresse I, Lüftner D, Späth-Schwalbe E, Buttgereit F (2002) Prevalence and clinical significance of anticardiolipin and anti-β2-glycoprotein-I antibodies in patients with non-Hodgkin’s lymphoma. Eur J Haematol 68(2):84–90PubMedCrossRefGoogle Scholar
  46. 46.
    Timuragaoglu A, Duman A, Ongut G, Saka O, Karadogan I (2000) The significance of autoantibodies in non-Hodgkin’s lymphoma. Leuk Lymphoma 40(1):119–122PubMedCrossRefGoogle Scholar
  47. 47.
    Manner H, Jung B, Tonassi L et al (2008) Successful treatment of catastrophic antiphospholipid syndrome (CAPS) associated with splenic marginal-zone lymphoma with low-molecular weight heparin, rituximab and bendamustine. Am J Med Ci 335:394–397CrossRefGoogle Scholar
  48. 48.
    Asherson RA, Espinosa G, Menahem S et al (2008) Relapsing catastrophic antiphsopholipid syndrome: report of three cases. Semin Arthristis Rheum 37:366–372CrossRefGoogle Scholar
  49. 49.
    Deane S, Meyers FJ, Gershwin ME (2008) On reversing the persistence of memory: hematopoietic stem cell transplant for autoimmune disease in the first ten years. J Autoimmun 30:180–196PubMedCrossRefGoogle Scholar
  50. 50.
    Boren EJ, Cheema GS, Naguwa SM, Ansari AA, Gershwin ME (2008) The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases. J Autoimmmun 30:90–98CrossRefGoogle Scholar
  51. 51.
    Ghia P, Scielzo C, Frenquelli M, Muzio M, Caligaris-Cappio F (2007) From normal to clonal B cells: chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and autoimmunity. Autoimmun Rev 7:127–131PubMedCrossRefGoogle Scholar
  52. 52.
    Ferraccioli G, Tolusso B (2007) Infections, B cell receptor activation and autoimmunity: different check-point impairments lead to autoimmunity, clonal B cell expansion and fibrosis in different immunological settings. Autoimmun Rev 7:109–113PubMedCrossRefGoogle Scholar
  53. 53.
    Gleicher N, Barad D, Weghofer A (2007) Functional autoantibodies, a new paradigm in autoimmunity. Autoimmun Rev 7:42–45PubMedCrossRefGoogle Scholar
  54. 54.
    Vollmers HP, Brarndlein S (2007) Natural antibodies and cancer. J Autoimmun 29:295–302PubMedCrossRefGoogle Scholar
  55. 55.
    Akatsuka T, Kobayashi N, Ishikawa T, Saito T, Shindo M, Yamauchi M et al (2007) Autoantibody response to microsomal epoxide hydrolase in hepatitis C and A. J Autoimmun 28:7–18PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Medical Clinic III, Institute of Transfusion MedicineUniversity Hospital, Johann Wolfgang Goethe-UniversityFrankfurtGermany

Personalised recommendations