Antiphospholipid Antibodies and Antiphospholipid Syndrome in Patients with Malignancies: Features, Incidence, Identification, and Treatment

ABSTRACT

Thrombotic events associated with antiphospholipid (aPL) antibodies can be the first manifestation of malignancy. The pathologic significance of aPL antibodies in patients with malignancies, however, is still unclear. It remains an unresolved issue as to whether the presence of aPL antibodies may be considered as an “epiphenomenon” of the malignancy itself or whether it contributes directly to the development of thrombosis in these patients.

In particular, solid tumors may be associated with the development of aPL antibodies, enhancing the thrombophilic risk in these patients. In general, routine anticoagulant prophylaxis with low-molecular-weight heparin in cancer patients with positive aPL antibodies is strongly indicated.

KEYWORDS

Malignancy - thrombosis - antiphospholipid syndrome - antiphospholipid antibodies - treatment

REFERENCES

• 1 Trousseau A. Phlegmasia alba dolens.  In: Clinique Medical de L'Hotel Dieu de Paris. Vol. 3 London, United Kingdom; The New Sydenham Society 1865: 94
• 2 Heit J A, Silverstein M D, Mohr D N et al.. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based control study.  Arch Intern Med. 2000;  160 809-815
• 3 Lee A Y, Levine M N. The thrombophilic state induced by therapeutic agents in the cancer patient.  Semin Thromb Hemost. 1999;  25 137-145
• 4 Blom J W, Doggen C J, Osanto S. Malignancies, prothrombotic mutations, and the risk of venous thrombosis.  JAMA. 2005;  293 715-722
• 5 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism.  Lancet Oncol. 2005;  6 401-410
• 6 Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of anticoagulation trial.  N Engl J Med. 2000;  342 1953-1958
• 7 Monreal M, Fernandez-Llamazares J, Perandreu J et al.. Occult cancer in patients with venous thromboembolism: which patients, which cancers.  Thromb Haemost. 1997;  78 1316-1318
• 8 Miyakis S, Lockshin M D, Atsumi T et al.. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome.  J Thromb Haemost. 2006;  4 295-306
• 9 Asherson R A. Antiphospholipid antibodies, malignancies and paraproteinemias.  J Autoimmun. 2000;  15 117-122
• 10 Asherson R A, Cervera R. Antiphospholipid antibodies and malignancies. In: Shoenfeld Y Cancer and Autoimmunity. Amsterdam, The Netherlands; Elsevier 2000: 93-102
• 11 Kazmierczak M, Lewandowski K, Wojtukiewicz M Z. Cancer proagulant in patients with adenocarcinomas.  Blood Coagul Fibrinolysis. 2005;  16 543-547
• 12 Langer F, Eifrig B, Hegewich-Becker S. Complicated antiphospholipid syndrome.  Dtsch Med Wochenschr. 2002;  127 1458-1462
• 13 Schreiber D P, Kepp D S. Axillary subclavian vein thrombosis following combination chemotherapy and radiation therapy in lymphoma.  Int J Radiat Oncol Biol Phys. 1986;  12 391-395
• 14 Ruffatti A, Avorsa A, Del Ross T et al.. Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome.  J Rheumatol. 1994;  21 2162-2163
• 15 Kozlowski C L, Johnson M J, Gorst D W et al.. Lung cancer, immune thrombocytopenia and the lupus inhibitor.  Postgrad Med J. 1987;  63 793-795
• 16 Papagiannis A, Cooper A, Bans J. Pulmonary embolism and lupus anticoagulant in a woman with renal cell carcinoma.  J Urol. 1994;  152 941-942
• 17 Park C J, Gho H I, Kim S I. A study of changes of coagulation inhibitors and fibrinolysis inhibitors in patients with liver cirrhosis and hepatoma.  J Korean Med Sci. 1991;  6 1-6
• 18 Asherson R A, D'Cruz D. Vascular occlusions in a patient with low positive antiphospholipid antibodies and subsequent development of breast carcinoma: a diagnostic dilemma.  Clin Rheumatol. 2007;  26 1531-1533
• 19 Stasi R, Stipa E, Masi M et al.. Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma.  Thromb Haemost. 1993;  70 568-572
• 20 Athale U H, Chan A K. Thrombosis in children with lymphoblastic leukemia Part III. Pathogenesis of thrombosis in children with acute lymphoblastic leukemia: effects of host environment.  Thromb Res. 2003;  111 321-327
• 21 Mouas H, Lortholary O, Eclache V et al.. Antiphospholipid syndrome during acute monocytic leukemia.  Eur J Haematol. 1994;  53 59-60
• 22 Orsino A, Schneider R, DeVeber G et al.. Childhood acute myelomonocytic leukemia (AML-M4) presenting as catastrophic antiphospholipid syndrome.  J Pediatr Hematol Oncol. 2004;  26 327-330
• 23 Zuckerman E, Toubi E, Golan T et al.. Increased thromboembolic incidence in anticardiolipin-positive patients with malignancy.  Br J Cancer. 1995;  72 447-451
• 24 Pusterla S, Previtali S, Marziali S et al.. Antiphospholipid antibodies in lymphoma: prevalence and clinical significance.  Hematol J. 2004;  5 341-346
• 25 Genvresse I, Lüftner D, Späth-Schwalbe E, Buttgereit F. Prevalence and clinical significance of anticardiolipin and anti-β2-glycoprotein-I antibodies in patients with non-Hodgkin's lymphoma.  Eur J Haematol. 2002;  68 84-90
• 26 Yoon K H, Wong A, Shakespeare T, Sivalingham P. High prevalence of the antiphospholipid antibodies in Asian cancer patients with thrombosis.  Lupus. 2003;  12 112-116
• 27 Gomez-Puerta J A, Cervera R, Espinosa G et al.. Antiphospholipid antibodies associated with malignancies: clinical and pathological characteristics of 120 patients.  Semin Arthritis Rheum. 2006;  35 322-332
• 28 Miesbach W, Scharrer I, Asherson R A. Thrombotic manifestations of the antiphospholipid syndrome in patients with malignancies.  Clin Rheumatol. 2006;  25 840-844
• 29 Miesbach W, Scharrer I, Asherson R A. High titres of IgM-antiphospholipid antibodies are unrelated to pathogenicity in patients with non-Hodgkin's lymphoma.  Clin Rheumatol. 2007;  26 95-97
• 30 Schved J F, Dupuy-Fons C, Biron C et al.. A prospective epdimiological study of the occurrence of antiphospholipid antibody; the Montpelier Antiphospholipid (MAP) Study.  Haemostasis. 1994;  24 175-182
• 31 Piette J-C, Cervera R, Levy R A, Nasonov E L, Triplett D A, Shoenfeld Y. The catastrophic antiphospholipid syndrome–Asherson's syndrome.  Ann Med Interne (Paris). 2003;  154 195-196
• 32 Asherson R A. The catastrophic antiphospholipid syndrome.  J Rheumatol. 1992;  19 508-512
• 33 Asherson R A, Cervera R, de Groot P G, Erkan D, Boffa M-C, Piett J C. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines.  Lupus. 2003;  12 530-534
• 34 Miesbach W, Asherson R A, Cervera R et al.. The role of malignancies in patients with catastrophic antiphospholipid (Asherson's) syndrome.  Clin Rheumatol. 2007;  26 2109-2114
• 35 Cervera R, Asherson R A, Acevedo M L et al.. Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients.  Ann Rheum Dis. 2004;  63 1312-1317
• 36 Cervera R, Espinosa G, Bucciarelli S, Gómez-Puerta J A, Font J. Lessons from the catastrophic antiphospholipid syndrome (CAPS) registry.  Autoimmun Dev. 2006;  6 81-84
• 37 Amital H, Levy Y, Davidson C et al.. Catastrophic antiphospholipid syndrome: remission following leg amputation in two cases.  Semin Arthritis Rheum. 2001;  31 127-132
• 38 Lee A Y, Levine M N, Baker R I et al.. Low-molecular-weight heparin versus coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.  N Engl J Med. 2003;  349 146-153
• 39 Hettiarachchi R J, Smorenburg S M, Ginsberg J et al.. Do heparins do more just treat thrombosis? The influence of heparins on cancer spread.  Thromb Haemost. 1999;  82 947-952
• 40 Meyer G, Marjanovic Z, Valcke J et al.. Comparison of low molecular weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study.  Arch Intern Med. 2002;  162 1729-1735