Clinical study and follow-up of 100 patients withthe antiphospholipid syndrome

doi:10.1016/S0049-0172(99)80029-8

Seminars in Arthritis and Rheumatism

Volume 29, Issue 3, December 1999, Pages 182-190

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https://doi.org/10.1016/S0049-0172(99)80029-8 Get rights and content

Abstract

Objectives:

To study the clinical characteristics at diagnosis and during follow-upof patients with the antiphospholipid syndrome (APS) and to analyze the influence of treatment on their outcome.

Patients:

One hundred patients with APS were included (86% female and 14%male; mean age, 36 years). Sixty-two percent had primary APS and 38% had APS associated with systemic lupus erythematosus (SLE). The median length of follow-up was 49 months.

Results:

Fifty-three percent of the patients had thromboses, 52% had thrombocytopenia, and 60% of the women had pregnancy losses. Patients with APS associated with SLE had a higher prevalence of hemolytic anemia (P = .02), thrombocytopenia (platelet count lower than 100 × 10⁹/L) (P = .004), antinuclear antibodies (P = .0002), and low complement levels. Fifty-three percent of the patients with thrombosis had recurrent episodes (86% in the same site as the previous thrombotic event). Recurrences were observed in 19% of the episodes treated with long-term oral anticoagulation, in 42% treated prophylactically with aspirin, and in 91% in which anticoagulant/antiaggregant treatment was discontinued (P = .0007). Multivariate analysis showed that prophylactic treatment and older age had an independent predictive value for rethrombosis. Prophylactic treatment during pregnancy (usually with aspirin) increased the live birth rate from 38% to 72% (P = .0002).

Conclusions:

Patients with APS have a high risk of recurrent thromboses. Long-term oral anticoagulation seems to be the best prophylactic treatment to prevent recurrences. Prophylactic treatment with aspirin during pregnancy reduced the rate of miscarriages remarkably.

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The Asia-Pacific League of Associations for Rheumatology consensus statements on the management of systemic lupus erythematosus
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Systemic lupus erythematosus (SLE) is prevalent in Asia and carries a variable prognosis among patients across the Asia-Pacific region, which could relate to access to health care, tolerability of medications, and adherence to therapies. Because many aspects of SLE are unique among patients from this region, the Asia-Pacific League of Associations for Rheumatology developed the first set of consensus recommendations on the management of SLE. A core panel of 13 rheumatologists drafted a set of statements through face-to-face meeting and teleconferences. A literature review was done for each statement to grade the quality of evidence and strength of recommendation. 29 independent specialists and three patients with SLE were then recruited for a modified Delphi process to establish consensus on the statements through an online voting platform. A total of 34 consensus recommendations were developed. Panellists agreed that patients with SLE should be referred to a specialist for the formulation of a treatment plan through shared decision making between patients and physicians. Remission was agreed to be the goal of therapy, but when it cannot be achieved, a low disease activity state should be aimed for. Patients should be screened for renal disease, and hydroxychloroquine is recommended for all Asian people with SLE. Major organ manifestations of SLE should be treated with induction immunosuppression and subsequently maintenance; options include cyclophosphamide, mycophenolate mofetil, azathioprine, and calcineurin inhibitors, in combination with glucocorticoids. Biologics, combination regimens, plasma exchange, and intravenous immunoglobulins should be reserved for cases of refractory or life-threatening disease. Anticoagulation therapy with warfarin is preferred to the direct oral anticoagulants for thromboembolic SLE manifestations associated with a high-risk antiphospholipid antibody profile.
The treatment of anti-phospholipid syndrome: A comprehensive clinical approach
2018, Journal of Autoimmunity
Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease that predisposes to thrombotic events and/or obstetric complications, in the persistent presence of anti-phospholipid antibodies (aPL). Life long moderate-intensity anticoagulation is the option of choice for aPL-positive patients with a previous thrombosis; critical issues concern the management of those with a history of arterial event due to the high rate of recurrence. Alternatives comprise anti-platelet agents and high-intensity anticoagulation. Low dose aspirin (LDASA) and low molecular weight heparin provide the mainstay of the treatment of obstetric APS, allowing a birth rate in 70% of cases. The management of refractory APS, thrombotic as well as obstetric, is highly debated, but an increasing burden of evidence points towards the beneficial effects of multiple treatments. Similarly, a management envisaging multiple drugs (anticoagulation, steroids, plasma exchange and/or intravenous immunoglobulins) is the most effective approach in catastrophic APS. Asymptomatic aPL carriers are at higher risk of thrombotic and obstetric complications compared to the general population, thus potentially benefitting of a pharmacological intervention. LDASA and hydroxychloroquine can be considered as options, in particular in case of high risk aPL profile, concomitant cardiovascular risk factors or associated autoimmune disease. APS is apparently a simple condition, but its multifaceted nature requires a complex and tailored treatment.
Obstetrical APS: Is there a place for additional treatment to aspirin–heparin combination?
2017, Gynecologie Obstetrique Fertilite et Senologie
Le syndrome des antiphospholipides (SAPL) est défini par l’association des manifestations thrombotiques et/ou d’une morbidité obstétricale associées à la présence d’anticorps antiphospholipides persistants (APL). L’association de l’aspirine à dose antiagrégante avec une héparine de bas poids moléculaire (HBPM) à dose prophylactique a permis d’améliorer considérablement le pronostic obstétrical au cours du SAPL primaire obstétrical. Plusieurs facteurs pourraient être associés à la survenue de complications obstétricales chez les patientes présentant un SAPL. L’existence d’une thrombose artérielle ou veineuse antérieure, d’un lupus associé, d’un SAPL avec un anticoagulant circulant (ACC) ou une triple positivité des antiphospholipides (ACC lupique avec un anticorps anticardiolipide et un anticorps anti-β2GP1) est associée à un mauvais pronostic obstétrical. En revanche, le SAPL obstétrical comportant des fausses couches précoces isolées est le plus souvent associé aux anticardiolipides isolés et son pronostic obstétrical est meilleur. Il faut noter qu’il n’y a pas de définition réellement établie de SAPL obstétrical réfractaire, qui pourrait être défini par une perte fœtale malgré un traitement par aspirine et HBPM bien conduit, en l’absence d’autres étiologies retrouvées et la fréquence de SAPL réfractaire ainsi défini serait de 20–39 %. Plusieurs traitements associés à la combinaison aspirine–HBPM ont été utilisés dans le SAPL obstétrical tel que les corticoïdes, l’hydroxychloroquine, les immunoglobulines intraveineuses et les échanges plasmatiques, d’autres traitements tel que l’eculizumab ou les statines pouvant avoir également un intérêt clinique, bien que des études soient nécessaires pour démontrer l’efficacité et la place de ces différentes stratégies.
Obstetrical APS is defined by thrombosis and/or obstetrical morbidity associated with persistent antiphospholipid antibodies. The aspirin and low molecular weighted heparin combination dramatically improved obstetrical outcome in APS patients. Several factors could be associated with obstetrical prognosis, as previous history of thrombosis, associated SLE, the presence of lupus anticoagulant and triple positivity of antiphospholipid antibodies. Obstetrical APS with isolated recurrent miscarriages is mostly associated with isolated anticardiolipids antibodies and have better obstetrical outcome. The pregnancy loss despite aspirin and heparin combination define the refractory obstetrical APS, and the prevalence could be estimated to 20–39%. Several other treatments have been used in small and open labeled studies, as steroids, intravenous immunoglobulins, plasma exchanges and hydroxychloroquine to improve the obstetrical outcome. Some other drugs as eculizumab and statins could also have physiopathological rational, but studies are necessary to define the place of these various drugs.
Rituximab usage in systemic lupus erythematosus-associated antiphospholipid syndrome: A single-center experience
2016, Seminars in Arthritis and Rheumatism
Although the data from primary antiphospholipid syndrome (APS) suggests a beneficial effect of rituximab usage, its therapeutic role remains to be defined in systemic lupus erythematosus (SLE)-associated APS, a complex clinical situation with thrombotic events and lupus activity.
A single-center retrospective analysis of rituximab usages in APS was performed in 800 hospitalized SLE patients.
There were 63 SLE-associated APS cases with 6 on rituximab therapy, all female aged 37.7 ± 9.0 years with 1 catastrophic and 16 thrombotic episodes. Therapeutic indications included warfarin failure despite the adequate target international normalized ratio with an average duration of 17.3 ± 11.2 months between the thrombotic recurrences. After the rituximab therapy, there was no relapse of thrombosis with a mean follow-up period of 39.3 ± 20.9 months, and a decrease in lupus activity (SLEDAI-2K, 9.7 ± 5.5 to 5.3 ± 2.2). Infection complications were observed, including episodes of bronchitis and urinary tract infection.
In this single-center study with largest case numbers and a long-term follow-up period, there were no recurrent thrombotic events after the rituximab therapy, implicating further consideration of large-scale trials enrolling more ethnic groups to evaluate its therapeutic role in SLE-associated APS patients.
Increased mortality in patients with the lupus anticoagulant: The vienna lupus anticoagulant and thrombosis study (LATS)
2015, Blood
Data on the clinical course of lupus anticoagulant (LA)–positive individuals with or without thrombotic manifestations or pregnancy complications are limited. To investigate mortality rates and factors that might influence mortality, we conducted a prospective observational study of LA-positive individuals. In total, 151 patients (82% female) were followed for a median of 8.2 years; 30 of the patients (20%) developed 32 thromboembolic events (15 arterial and 17 venous events) and 20 patients (13%) died. In univariable analysis, new onset of thrombosis (hazard ratio [HR] = 8.76; 95% confidence interval [CI], 3.46-22.16) was associated with adverse survival. Thrombosis remained a strong adverse prognostic factor after multivariable adjustment for age and hypertension (HR = 5.95; 95% CI, 2.43-14.95). Concomitant autoimmune diseases, anticoagulant treatment at baseline, or positivity for anticardiolipin- or anti-β2-glycoprotein I antibodies were not associated with mortality. In a relative survival analysis, our cohort of LA positives showed a persistently worse survival in comparison with an age-, sex-, and study-inclusion-year–matched Austrian reference population. The cumulative relative survival was 95.0% (95% CI, 88.5-98.8) after 5 years and 87.7% (95% CI, 76.3-95.6) after 10 years. We conclude that occurrence of a thrombotic event is associated with higher mortality in patients with LA. Consequently, the prevention of thromboembolic events in LA positives might improve survival.
Recommendations of the Spanish Rheumatology Society for Primary Antiphospholipid Syndrome. Part I: Diagnosis, Evaluation and Treatment
2020, Reumatologia Clinica
La dificultad para el diagnóstico y la variedad de manifestaciones clínicas que pueden determinar la elección del tratamiento del síndrome antifosfolípido (SAF) primario ha impulsado a la Sociedad Española de Reumatología (SER) en la elaboración de recomendaciones basadas en la mejor evidencia posible. Estas recomendaciones pueden servir de referencia para reumatólogos y otros profesionales implicados en el manejo de pacientes con SAF.
Se creó un panel formado por cuatro reumatólogos, una ginecóloga y una hematóloga, expertos en SAF, previamente seleccionados mediante una convocatoria abierta o por méritos profesionales. Las fases del trabajo fueron: identificación de las áreas claves para la elaboración del documento, análisis y síntesis de la evidencia científica (utilizando los niveles de evidencia del Scottish Intercollegiate Guidelines Network [SIGN]) y formulación de recomendaciones a partir de esta evidencia y de técnicas de «evaluación formal» o «juicio razonado».
Se han elaborado 46 recomendaciones que abordan cinco áreas principales: diagnóstico y evaluación, medidas de tromboprofilaxis primaria, tratamiento del SAF primario o tromboprofilaxis secundaria, tratamiento del SAF obstétrico y situaciones especiales. Se incluye también el papel de los nuevos anticoagulantes orales, el problema de las recurrencias o los principales factores de riesgo identificados en estos individuos. En este documento se reflejan las 21 primeras recomendaciones, referidas a las áreas de diagnóstico, evaluación y tratamiento del SAF primario. El documento contiene una tabla de recomendaciones y algoritmos de tratamiento.
Se presentan las recomendaciones de la SER sobre SAF primario. Este documento corresponde a la parte I, relacionada con el diagnóstico, la evaluación y el tratamiento. Estas recomendaciones se consideran herramientas en la toma de decisiones para los clínicos, teniendo en consideración tanto la decisión del médico experto en SAF como la opinión compartida con el paciente. Se ha elaborado también una parte II, que aborda aspectos relacionados con el SAF obstétrico y situaciones especiales.
The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS.
A panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques).
46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms.
An update of the SER recommendations on APS is presented. This document corresponds to part I, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A part II has also been prepared, which addresses aspects related to obstetric SAF and special situations.

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^*: Supported by Spanish grants FIS 96/0580, FIS 97/0525, andFIS 98/0171. EJ. Munoz-Rodriguez was a research fellow sponsored by a grant from the Hospital Clinic of Barcelona.

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Clinical study and follow-up of 100 patients withthe antiphospholipid syndrome*

Abstract

Objectives:

Patients:

Results:

Conclusions:

Semin Arthritis Rheum

Am J Kidney Dis

Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Antiphospholipid antibodies and antiphospholipid syndrome

Curr Opin Rheumatol

The “primary” antiphospholipid syndrome: major clinical and serological features

Medicine (Baltimore)

Anticardiolipin antibodies in patients with autoimmune diseases: isotype distribution and clinical associations

Clin Rheumatol

Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1000 patients

Medicine (Baltimore)

Immunology of the antiphospholipid antibody syndrome

Arthritis Rheum

Reactivity to beta-2-glycoprotein I clearly differentiates anticardiolipin antibodies from antiphospholipid syndrome and syphilis

Thromb Haemost

Clinical and serological features of the antiphospholipid syndrome (APS)

Br J Rheumatol

The 1982 revised criteria for the classification of systemic lupus erythematosus

Arthritis Rheum

Anticardiolipin antibodies: isotype distribution and phospholipid specificity

Ann Rheum Dis

Triplett DA. Laboratory identification of lupus anticoagulants: results of The Second International Workshop for identification of lupus anticoagulants

Thromb Haemost

Platelet autoantibodies detected by immunoblotting in systemic lupus erythematosus: association with the lupus anticoagulant, and with history ofthrombosis and thrombocytopenia

Eur J Haematol

Specific antiplatelet antibodies in patients with antiphospholipid antibodies and thrombocytopenia

Eur J Haemato1

Hemocytopenia in systemic lupus erythematosus: relationship to antiphospholipid antibodies

J Rheumatol

The role of anticardiolipin autoanfibodies in the pathogenesis of autoimname hemolytic anemia in systemic lupus erythematosus

J Rheumatol