Portal de Periódicos da CAPES

Antiphospholipid Syndrome in the Elderly: Caution

1998; Lippincott Williams & Wilkins; Volume: 97; Issue: 22 Linguagem: Inglês

10.1161/01.cir.97.22.2195

1524-4539

Jean‐Charles Piette, P. Cacoub,

Liver Diseases and Immunity

HomeCirculationVol. 97, No. 22Antiphospholipid Syndrome in the Elderly: Caution Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBAntiphospholipid Syndrome in the Elderly: Caution Jean-Charles Piette and Patrice Cacoub Jean-Charles PietteJean-Charles Piette From the Service de Médecine Interne, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. and Patrice CacoubPatrice Cacoub From the Service de Médecine Interne, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. Originally published9 Jun 1998https://doi.org/10.1161/01.CIR.97.22.2195Circulation. 1998;97:2195–2196Ten years after its identification, thousands of articles and 2 books have made the APS popular. Subsequently, the diagnosis of a possible APS is now frequently considered in daily practice, not only by subspecialists but also by general practitioners, in patients with thrombosis, sometimes whatever their age at the time of the first vascular event. We wish to emphasize here the potential hazards associated with a diagnosis of APS in elderly patients.Historically, APS was first identified as a subset of patients with SLE because of the strong association observed in this disorder between the occurrence of thrombosis, either arterial or venous, and/or miscarriages and the presence of aPL (ie, Lupus anticoagulant) and/or aCL. Later, APS was also recognized in patients who had no features of SLE, leading to the concept of a "primary APS."1 A set of criteria has been proposed to discriminate primary from SLE-related APS.2 Although aPL may be encountered in multiple circumstances, primary and SLE-related appear to be the 2 major variants of APS.234APS usually affects young patients. This is obviously true for SLE-related APS, given that spontaneously occurring SLE is restricted primarily to women with functional ovaries. This also applies to primary APS, as illustrated by data summarized in the Table. In reported series,1345678910 the first vascular event usually occurs in young adults and rarely in people >60 years old. This age distribution not only reflects a possible bias, ie, the younger the age at first thrombosis, the higher the likelihood of having extensive coagulation tests performed to determine its cause, but also the uncertain significance of positive tests for aPL in the elderly. On the one hand, although data in the literature remain scarce and conflicting, it has been suggested that the prevalence of aCL increases with age in normal subjects.11 On the other hand, aPL are commonly found in a wide range of situations that frequently occur in the elderly, such as long-term administration of diverse drugs,2 rheumatoid factor,12 monoclonal gammopathy of uncertain origin,13 advanced renal or hepatic dysfunction,1415 polymyalgia rheumatica/temporal arteritis,16 myeloproliferative disorders, lymphomas, and solid cancers.21718 For example, in a prospective epidemiological study performed in a department of internal medicine on 1014 patients, 70 (mean age, 69 years) had aPL; among these, cancer was found in 14 and was the most frequent associated disease.17 In the Italian registry on aPL, of 360 patients or subjects, 4 developed non-Hodgkin's lymphoma during follow-up.19 Malignancies are a major concern indeed, given that venous thrombosis, especially when recurrent, may be their presenting manifestation. Similarly, a paraneoplastic "marantic" endocarditis may masquerade as an aPL-related valvulopathy complicated by multiple emboli.20 Furthermore, it has been shown not only that aCL are more prevalent in patients with various forms of malignancies compared with healthy control subjects but also that among the former, aCL, especially in high titers, are associated with a higher incidence of thromboembolic events.18 The risk exists that positive determinations of aPL may lead physicians to consider a diagnosis of primary APS and prevent them from looking for a possible occult malignancy. In this setting, it should be recalled that APS cannot be considered an explanation for long-lasting fever, sweating, weight loss (except in the rare case of APS-related chronic adrenal failure), or spleen enlargement not due to portal hypertension.2The last point to be discussed is management. Prospective trials are not yet available, but all retrospective studies strongly suggest that recurrent thrombotic events can be efficiently prevented by long-term anticoagulation, especially when aimed at an international normalized ratio of ≥3.348 Serious bleeding may sometimes occur, but it is assumed that the risk/benefit ratio favors the use of this regimen.4 However, it should be kept in mind that these data have been obtained from series of young patients with primary or SLE-related APS. Age has been demonstrated to be a risk factor for severe bleeding episodes in patients placed on long-term anticoagulation,21 and we have similar experience in APS. Therefore, the relevance of this regimen remains to be demonstrated in elderly patients with APS. Whether or not "true" primary APS occurs de novo after the age of 60 years, an answer is expected for the aging cohort of patients with clear-cut APS who remain recurrence-free under oral anticoagulation but persistently have demonstrable aPL.In conclusion, additional data on aPL in the elderly are needed. Within this population, several cross-sectional studies have suggested that the presence of aCL might be an independent risk factor for a precise thrombotic event, such as ischemic stroke.22 In an individual patient, however, the diagnosis of APS requires more than a single low-positive determination.2 To date, primary APS should be regarded as a disease that affects mainly young or middle-aged adults. In elderly patients presenting with thrombosis and repeatedly positive tests for aPL, a possible underlying disorder needs to be considered, especially hematological or solid malignancy. Ongoing studies will demonstrate whether other biological markers, such as antibodies directed at β2-glycoprotein I or prothrombin, might help to distinguish, among aPL, those who belong to the autoimmune/thrombogenic subset from those who are just an epiphenomenon.12 In daily practice, because of its potential hazards, long-term anticoagulation should be discussed on an individual basis in elderly patients with APS.Selected Abbreviations and AcronymsaCL=anticardiolipin antibodiesaPL=antiphospholipid antibodiesAPS=antiphospholipid syndromeSLE=systemic lupus erythematosusThe opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. Table 1. Age (Years) at First Thrombosis (Unless Specified) in Patients With Primary APSAuthor (Reference)YearnMean±SDRangeAsherson (1)119897038.521–59Font (5)19911132.7±1122–55Rosove (3)219927045.5±17Vianna (6)119945832±10Khamashta (4)31995623518–66Cabral (7)19951032.9±1020–49Krnic-Barrie (8)1419973541.2±15Piette (9)19986133.8±1210–65Asherson (10)519982841.4±1417–741Also included women with recurrent miscarriages only: 4% in Reference 1, low but not specified in References 6 and 8.2APS was of the primary form in only 73% of patients. Age was not explicitly referred to as age at first vascular event.3Age was median, not mean.4Age at APS diagnosis.5Age at occurrence of "catastrophic" APS. Before catastrophic APS, the oldest patient had a 17-year history of recurrent venous thrombosis/pulmonary embolism.FootnotesCorrespondence to Jean-Charles Piette, Service de Médecine Interne, Groupe Hospitalier Pitié-Salpêtrière, 83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. E-mail [email protected] References 1 Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RHW, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GRV. The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore).1989; 68:366–374.CrossrefMedlineGoogle Scholar2 Piette JC. Diagnostic and classification criteria for the antiphospholipid/cofactors syndrome: a "mission impossible"? Lupus.1996; 5:354–363.CrossrefMedlineGoogle Scholar3 Rosove MH, Brewer PMC. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med.1992; 117:303–308.CrossrefMedlineGoogle Scholar4 Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med.1995; 332:993–997.CrossrefMedlineGoogle Scholar5 Font J, Lopez-Soto A, Cervera R, Balasch J, Pallares L, Navarro M, Bosch X, Ingelmo M. The "primary" antiphospholipid syndrome: antiphospholipid antibody pattern and clinical features of a series of 23 patients. Autoimmunity.1991; 9:69–75.CrossrefMedlineGoogle Scholar6 Vianna JL, Khamashta MA, Ordi-Ros J, Font J, Cervera R, Lopez-Soto A, Tolosa C, Franz J, Selva A, Ingelmo M, Vilardell M, Hughes GRV. Comparison of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. Am J Med.1994; 96:3–9.CrossrefMedlineGoogle Scholar7 Cabral AR, Cabiedes J, Alarcon-Segovia D. Antibodies to phospholipid-free beta(2)-glycoprotein-I in patients with primary antiphospholipid syndrome. J Rheumatol.1995; 22:1894–1898.MedlineGoogle Scholar8 Krnic-Barrie S, O'Connor CR, Looney SW, Pierangeli SS, Harris EN. A retrospective review of 61 patients with antiphospholipid syndrome: analysis of factors influencing recurrent thrombosis. Arch Intern Med.1997; 157:2101–2108.CrossrefMedlineGoogle Scholar9 Piette JC, Frances C, Papo T, Amoura Z, Musset L, Horellou MH. Gender influences features of the primary antiphospholipid syndrome [abstract]. Lupus. 1998;7(suppl 1):47. Abstract 125.Google Scholar10 Asherson RA, Cervera R, Piette JC, Font J, Lie JT, Burcoglu A, Lim K, Munoz FJ, Levy RA, Boue F, Rossert J, Ingelmo M. "Catastrophic" antiphospholipid syndrome: clinical and laboratory features of 50 patients. Medicine (Baltimore).1998; 77:195–207.CrossrefMedlineGoogle Scholar11 Petri M. Epidemiology of the antiphospholipid syndrome. In: Asherson RA, Cervera R, Piette JC, Shoenfeld Y, eds. The Antiphospholipid Syndrome. Boca Raton, Fla: CRC Press; 1996;13–28.Google Scholar12 Guerin J, Feighery C, Sim RB, Jackson J. Antibodies to β2-glycoprotein I: a specific marker for the antiphospholipid syndrome. Clin Exp Immunol.1997; 109:304–309.CrossrefMedlineGoogle Scholar13 Krause I, Cohen J, Blank M, Bakimer R, Cartman A, Hohmann A, Valesini G, Asherson RA, Khamashta MA, Hughes GRV, Shoenfeld Y. Distribution of two common idiotypes of anticardiolipin antibodies in sera of patients with primary antiphospholipid syndrome, systemic lupus erythematosus and monoclonal gammopathies. Lupus.1992; 1:91–96.CrossrefMedlineGoogle Scholar14 Piette JC, Cacoub P, Wechsler B. Renal manifestations of the antiphospholipid syndrome. Semin Arthritis Rheum.1994; 23:357–366.CrossrefMedlineGoogle Scholar15 Quintarelli C, Ferro D, Valesini G, Basili S, Tassone G, Violi F. Prevalence of lupus anticoagulant in patients with cirrhosis: relationship with beta-2-glycoprotein I plasma levels. J Hepatol.1994; 21:1086–1091.CrossrefMedlineGoogle Scholar16 Chakravarty K, Pountain G, Merry P, Byron M, Hazleman B, Scott DGI. A longitudinal study of anticardiolipin antibody in polymyalgia rheumatica and giant cell arteritis. J Rheumatol.1995; 22:1694–1697.MedlineGoogle Scholar17 Schved JF, 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.MedlineGoogle Scholar18 Zuckerman E, Toubi E, Golan TD, Rosenvald-Zuckerman T, Sabo E, Shmuel Z, Yeshurun D. Increased thromboembolic incidence in anti-cardiolipin-positive patients with malignancy. Br J Cancer.1995; 72:447–451.CrossrefMedlineGoogle Scholar19 Finazzi G, Brancaccio V, Moia M, Ciavarella N, Mazzucconi MG, Schinco PC, Ruggeri M, Pogliani EM, Gamba G, Rossi E, Baudo F, Manotti C, D'Angelo A, Palareti G, De Stefano V, Berrettini M, Barbui T. 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.CrossrefMedlineGoogle Scholar20 Bessis D, Sotto A, Viard JP, Béerard M, Ciurana AJ, Boffa MC. Trousseau's syndrome with nonbacterial thrombotic endocarditis: pathogenic role of antiphospholipid syndrome. Am J Med.1995; 98:511–513.CrossrefMedlineGoogle Scholar21 Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Musolesi S, on behalf of the Italian Study on Complications of Oral Anticoagulant Therapy. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet.1996; 348:423–428.CrossrefMedlineGoogle Scholar22 Antiphospholipid Antibodies In Stroke Study Group. Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. Neurology.1993; 43:2069–2073.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails June 9, 1998Vol 97, Issue 22Article InformationMetrics Download: 386 Copyright © 1998 by American Heart Associationhttps://doi.org/10.1161/01.CIR.97.22.2195 Originally publishedJune 9, 1998 KeywordsEditorialsagingthrombosisimmunologycoagulationPDF download