Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2006:9–21. doi: 10.1007/1-84628-009-5_2

Antiphospholipid (Hughes) Syndrome: An Overview

David P D’Cruz 2
Editor: M A Khamashta1
PMCID: PMC7123322

Conclusion

In conclusion, the following observations can be made. aPL are present in approximately 2% to 4% of the normal population and the prevalence increases with age. There is a high prevalence among patients with autoimmune connective tissue disorders, especially SLE. There is an association with both venous and arterial thrombosis as well as with pregnancy morbidity, but the strength of association varies amongst studies. This probably reflects different populations, study designs, and different assays and definitions used. In several studies the risk of thrombosis appears to be higher with LA and the data suggests a true association rather than epiphenomenon. In a given patient, both aCL and LA should be measured. A significant impact on long-term survival has been noted and aPL also contribute significantly to accumulated damage in diseases such as SLE. The clinical spectrum of APS features is enormous and continues to expand. It behoves us all as clinicians and health care professionals to consider an early diagnosis of Hughes syndrome, with its distinct clinical and serological features, to reduce the risk of morbidity and mortality in our patients.

Keywords: Systemic Lupus Erythematosus, Systemic Lupus Erythematosus Patient, Lupus Anticoagulant, Anticardiolipin Antibody, Pregnancy Morbidity

References

  • 1.Cervera R., Khamashta M.A., Font J., et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1000 patients. Medicine. 1993;72:113–124. [PubMed] [Google Scholar]
  • 2.Perez-Vazquez M.E., Villa A., Drenkard C., Cabiedes J., Alarcon-Segovia D. Influence of disease duration, continued follow up and further antiphopholipid testing on the frequency and classi fication category of antiphospholipid syndrome in a cohort of patients with SLE. J Rheumatol. 1993;20:437–442. [PubMed] [Google Scholar]
  • 3.Cervera R., Piette J.C., Font J., et al. Antiphospholipid syndrome. Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum. 2002;46:1019–1027. doi: 10.1002/art.10187. [DOI] [PubMed] [Google Scholar]
  • 4.Wilson W.A., Gharavi A.E., Koike T., et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Report of an International Workshop. Arthritis Rheum. 1999;42:1309–1311. doi: 10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  • 5.Lockshin M.D., Sammaritano L.R., Schwartzman S. Validation of the Sapporo criteria for the antiphospholipid syndrome. Arthritis Rheum. 2000;43:440–443. doi: 10.1002/1529-0131(200002)43:2<440::AID-ANR26>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  • 6.Alarcon-Segovia D., Deleze M., Oria C.V., et al. Antiphospholipid antibodies and the antiphospholipid syndrome in SLE. A prospective analysis of 500 consecutive patients. Medicine. 1989;68:353–365. doi: 10.1097/00005792-198911000-00003. [DOI] [PubMed] [Google Scholar]
  • 7.Cervera R., Khamashta M.A., Font J., et al. Morbidity and mortality in systemic lupus erythematosus during a 10 year period. A comparison of early and late manifestations in a cohort of 1000 patients. Medicine. 2003;82:299–308. doi: 10.1097/01.md.0000091181.93122.55. [DOI] [PubMed] [Google Scholar]
  • 8.Kovalevsky G., Gracia C.R., Berlin J.A., Sammel M.D., Barnhart K.T. Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med. 2004;164:558–563. doi: 10.1001/archinte.164.5.558. [DOI] [PubMed] [Google Scholar]
  • 9.Drenkard C., Sanchez-Guerrero J., Alarcon-Segovia D. Fall in antiphospholipid antibody at time of thromboocclusive episodes in SLE. J Rheumatol. 1989;16:614–617. [PubMed] [Google Scholar]
  • 10.Perez-Vazquez M.E., Cabiedes J., Cabral A.R., Alarcon-Segovia D. Decrease in serum antiphospholipid antibodies upon development of the nephrotic syndrome in patients with SLE: relationship to urinary losses of IgG and other factors. Am J Med. 1992;92:357–363. doi: 10.1016/0002-9343(92)90264-C. [DOI] [PubMed] [Google Scholar]
  • 11.Silveira L.H., Jara L.J., Espinoza L.R. Transient disappearance of serum antiphospholipid antibodies can also be due to prednisolone therapy. Clin Exp Rheumatol. 1996;14:217–226. [PubMed] [Google Scholar]
  • 12.McClain M.T., Arbuckle M.R., Heinlen L.D., et al. The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus. Arthritis Rheum. 2004;50:1226–1232. doi: 10.1002/art.20120. [DOI] [PubMed] [Google Scholar]
  • 13.Diri E., Curcurull E., Gharavi A.E., et al. Antiphospholipid (Hughes) syndrome in African-American patients: IgA aCL and beta 2 glycoprotein 1 is the most frequent isotype. Lupus. 1999;8:263–268. doi: 10.1191/096120399678847812. [DOI] [PubMed] [Google Scholar]
  • 14.Bertolaccini M.L., Atsumi T., Amengual O., Katsumata K., Khamashta M.A., Hughes G.R.V. IgA anticardiolipin antibody testing does not contribute to the diagnosis of antiphospholipid syndrome in patients with SLE. Lupus. 1998;7(suppl 2):S184. [Google Scholar]
  • 15.Fields R., Toubbeh H., Searles R., Bankhurst A. The prevalence of anticardiolipin antibodies in a healthy elderly population and its association with antinuclear antibodies. J Rheumatol. 1989;16:623–625. [PubMed] [Google Scholar]
  • 16.Antiphospholipid Antibodies in Stroke Study Group Clinical, radiological, and pathological aspects of cerebrovascular disease associated with antiphospholipid antibodies. Stroke. 1993;24(suppl 1):S1–S123. [PubMed] [Google Scholar]
  • 17.Schved J.F., Dupuy-Fons C., Biron C., Quere I., Janbon C. A prospective epidemiological study on the occurrence of antiphospholipid antibody: the Montpellier Antiphospholipid (MAP) Study. Haemostasis. 1994;24:175–182. doi: 10.1159/000217099. [DOI] [PubMed] [Google Scholar]
  • 18.Schulman S., Svenungsson E., Granqvist S., the Duration of Anticoagulation Study Group Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med. 1998;104:332–338. doi: 10.1016/S0002-9343(98)00060-6. [DOI] [PubMed] [Google Scholar]
  • 19.Nencini P., Baruffi M., Abbate R., Massai G., Amaducci L., Inzitari D. Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischaemia. Stroke. 1992;23:189–193. doi: 10.1161/01.str.23.2.189. [DOI] [PubMed] [Google Scholar]
  • 20.Vaarala O., Puurunen M., Manttari M., et al. Anticardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation. 1995;91:23–27. doi: 10.1161/01.cir.91.1.23. [DOI] [PubMed] [Google Scholar]
  • 21.Kearon C., Gent M., Hirsh J., Weitz J., et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340:901–907. doi: 10.1056/NEJM199903253401201. [DOI] [PubMed] [Google Scholar]
  • 22.Wahl D.G., Guillemin F., de Maistre E., Perret-Guillaume C., Lecompte T., Thibaut G. Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus. 1998;7:15–22. doi: 10.1191/096120398678919688. [DOI] [PubMed] [Google Scholar]
  • 23.Ginsburg K., Liang M., Newcomer L., et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992;117:997–1002. doi: 10.7326/0003-4819-117-12-997. [DOI] [PubMed] [Google Scholar]
  • 24.Janardhan V., Wolf P.A., Kase C.S., et al. Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack. The Framingham cohort and offspring study. Stroke. 2004;35:736–741. doi: 10.1161/01.STR.0000117575.48205.2D. [DOI] [PubMed] [Google Scholar]
  • 25.Levine S.R., Brey R.L., Tilley B.C., et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA. 2004;291:576–584. doi: 10.1001/jama.291.22.2702. [DOI] [PubMed] [Google Scholar]
  • 26.Kittner S., Gorelick P. Antiphospholipid antibodies and stroke: an epidemiological perspective. Stroke. 1992;23(suppl 1):1–19. [PubMed] [Google Scholar]
  • 27.Cervera R., Khamashta M.A., Font J., et al. Morbidity and mortality in systemic lupus erythematosus during a 5 year period. A multicentre prospective study of 1000 patients. Medicine. 1999;78:167–175. doi: 10.1097/00005792-199905000-00003. [DOI] [PubMed] [Google Scholar]
  • 28.Wahl D.G., Guillemin F., de Maistre E., Perret C., Lecompte T., Thibaut G. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus. A meta-analysis. Lupus. 1997;6:467–473. doi: 10.1177/096120339700600510. [DOI] [PubMed] [Google Scholar]
  • 29.Shah N.M., Khamashta M.A., Atsumi T., Hughes G.R.V. Outcome of patients with anticardiolipin antibodies: a 10 year follow up of 52 patients. Lupus. 1998;7:3–6. doi: 10.1191/096120398678919624. [DOI] [PubMed] [Google Scholar]
  • 30.Jouhikainen T., Stephansson E., Leirisalo-Repo M. Lupus anticoagulant as a prognostic marker in systemic lupus erythematosus. Br J Rheumatol. 1993;32:568–573. doi: 10.1093/rheumatology/32.7.568. [DOI] [PubMed] [Google Scholar]
  • 31.Soares M., Reis L., Papi J.A., Cardoso C.R. Rate, pattern and factors related to damage in Brazilian systemic lupus erythematosus patients. Lupus. 2003;12:788–794. doi: 10.1191/0961203303lu447xx. [DOI] [PubMed] [Google Scholar]
  • 32.Ruiz-Irastorza G., Egurbide M.V., Ugalde J., Aguirre C. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med. 2004;164:77–82. doi: 10.1001/archinte.164.1.77. [DOI] [PubMed] [Google Scholar]
  • 33.Finazzi G., Brancaccio V., Moia M., et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies. A four year prospective study from the Italian Registry. Am J Med. 1996;100:530–536. doi: 10.1016/S0002-9343(96)00060-5. [DOI] [PubMed] [Google Scholar]
  • 34.Neville C., Rauch J., Kassis J., et al. Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies. Thromb Haemost. 2003;90:108–115. [PMC free article] [PubMed] [Google Scholar]
  • 35.Khamashta M., Cuadrado M., Mujic F., Taub N., Hunt B., Hughes G.R.V. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. 1995;332:993–997. doi: 10.1056/NEJM199504133321504. [DOI] [PubMed] [Google Scholar]
  • 36.Giron-Gonzalez J.A., Garcia del Rio E., Rodriguez C., Rodriguez-Martorell J., Serrano A. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004;31:1560–1567. [PubMed] [Google Scholar]
  • 37.Roman M.J., Shanker B.A., Davis A., et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349:2399–2406. doi: 10.1056/NEJMoa035471. [DOI] [PubMed] [Google Scholar]
  • 38.Medina G., Casaos D., Jara L.J., Vera-Lastra O., Fuentes M., Barile L., Salas M. Increased carotid artery intima-media thickness may be associated with stroke in primary antiphospholipid syndrome. Ann Rheum Dis. 2003;62:607–610. doi: 10.1136/ard.62.7.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Baron M., D’Cruz D.P., Khamashta M.A., Hughes G.R.V. ABI in PAPS. Ann Rheum Dis. 2005;64:144. doi: 10.1136/ard.2003.016204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Sangle S.R., D’Cruz D.P., Jan W., Karim M.Y., Khamashta M.A., Abbs I.C., Hughes G.R. Renal artery stenosis in the antiphospholipid (Hughes) syndrome and hypertension. Ann Rheum Dis. 2003;62:999–1002. doi: 10.1136/ard.62.10.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Vaz J.L., Dancour M.A., Bottino D.A., Bouskela E. Nailfold videocapillaroscopy in primary antiphospholipid syndrome (PAPS) Rheumatology. 2004;43:1025–1027. doi: 10.1093/rheumatology/keh233. [DOI] [PubMed] [Google Scholar]
  • 42.Rosendaal F. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost. 1997;78:1–6. doi: 10.1159/000134614. [DOI] [PubMed] [Google Scholar]
  • 43.Brenner B., Vulfsons S.L., Lanir N., Nahir M. Coexistence of familial antiphospholipid syndrome and factor V Leiden: impact on thrombotic diathesis. Br J Haematol. 1996;94:166–167. doi: 10.1046/j.1365-2141.1996.d01-1757.x. [DOI] [PubMed] [Google Scholar]
  • 44.Ames P., Tommasino C., D’Andrea G., Iannaccone L., Brancaccio V., Margaglione M. Thrombophilic genotypes in subjects with idiopathic antiphospholipid antibodies — prevalence and significance. Thromb Haemost. 1998;79:46–49. [PubMed] [Google Scholar]
  • 45.Peddi V.R., Kant K.S. Catastrophic secondary antiphospholipid syndrome with concomitant antithrombin III deficiency. J Am Soc Nephrol. 1995;5:1882–1887. doi: 10.1681/ASN.V5111882. [DOI] [PubMed] [Google Scholar]
  • 46.Asherson R.A., Khamashta M.A., Ordi-Ros J., et al. The primary antiphospholipid syndrome: major clinical and serological features. Medicine. 1989;68:366–374. [PubMed] [Google Scholar]
  • 47.Soweid A.M., Hajjar R.R., Hewan-Lowe K.O., Gonzalez E.B. Skin necrosis indicating antiphospholipid syndrome in patient with AIDS. S Med J. 1995;88:786–778. doi: 10.1097/00007611-199507000-00022. [DOI] [PubMed] [Google Scholar]
  • 48.Labarca J., Rabaggliati R., Radrigan F., et al. Antiphospholipid syndrome associated with cytomegalovirus infection: case report and review. Clin Infect Dis. 1997;24:197–200. doi: 10.1093/clinids/24.2.197. [DOI] [PubMed] [Google Scholar]
  • 49.Merrill J.T., Shen C., Gugnani M., Lahita R.G., Mongey A.B. High prevalence of antiphospholipid antibodies in patients taking procainamide. J Rheumatol. 1997;24:1083–1088. [PubMed] [Google Scholar]
  • 50.Vianna J.L., Khamashta M.A., Ordi-Ros J., et al. Comparison of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. Am J Med. 1994;96:3–9. doi: 10.1016/0002-9343(94)90108-2. [DOI] [PubMed] [Google Scholar]
  • 51.Piette J.C., Weschler B., Frances C., Papo T., Godeau P. Exclusion criteria for primary antiphospholipid syndrome. J Rheumatol. 1993;20:1802–1804. [PubMed] [Google Scholar]
  • 52.Karassa F.B., Bijl M., Davies K.A., et al. Role of the Fcgamma receptor IIA polymorphism in the antiphospholipid syndrome: an international meta-analysis. Arthritis Rheum. 2003;48:1930–1938. doi: 10.1002/art.11059. [DOI] [PubMed] [Google Scholar]
  • 53.Seisdedos L., Munoz-Rodriguez F. J., Cervera R., Font J., Ingelmo M. Primary antiphospholipid syndrome evolving into SLE. Lupus. 1997;6:285–286. doi: 10.1177/096120339700600314. [DOI] [PubMed] [Google Scholar]
  • 54.Carbone J., Orera M., Rodriguez-Mahou M., et al. Immunological abnormalities in primary APS evolving into SLE: 6 years follow-up in women with repeated pregnancy loss. Lupus. 1999;8:274–8. doi: 10.1191/096120399678847777. [DOI] [PubMed] [Google Scholar]
  • 55.Silver R.M., Drapor M.J., Scott J.R., et al. Clinical consequences of antiphospholipid antibodies. An historic exhort study Obstet Gynecol. 1994;83:372–77. [PubMed] [Google Scholar]
  • 56.Mujic F., Cuadrado M.J., Lloyd M., et al. Primary antiohospholipid syndrome evolving into SLE. J Rheumatol. 1995;22:1589–1592. [PubMed] [Google Scholar]
  • 57.Hughes G.R., Khamashta M.A. Seronegative antiphospholipid syndrome. Ann Rheum Dis. 2003;62:1127. doi: 10.1136/ard.2003.006163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Erkan D., Cervera R., Asherson R.A. Catastrophic antiphospholipid syndrome: where do we stand? Arthritis Rheum. 2003;48:3320–3327. doi: 10.1002/art.11359. [DOI] [PubMed] [Google Scholar]

Articles from Hughes Syndrome are provided here courtesy of Nature Publishing Group

RESOURCES