Serological evolution in women with positive antiphospholipid antibodies

doi:10.1016/j.semarthrit.2017.05.001

Seminars in Arthritis and Rheumatism

Volume 47, Issue 3, December 2017, Pages 397-402

https://doi.org/10.1016/j.semarthrit.2017.05.001 Get rights and content

Abstract

Objectives

To explore the clinical and serological course of fertile women with positive antiphospholipid (aPL), and the factors and therapeutic implications associated with aPL negativization.

Methods

Retrospective study including 105 women with a positive aPL serology between 1995 and 2013 attending the obstetric autoimmune pathology clinic of a tertiary facility. Patients were classified into the following 3 groups: patients with primary antiphospholipid syndrome (pAPS, 49), patients with a positive serology for aPL, not meeting clinical criteria (42), and patients with systemic lupus erythematosus and a positive aPL serology (14). They were also classified according to the serological aPL evolution: persistently negative aPL, transiently positive serology, and persistently positive serology according to established criteria.

Results

After a mean follow-up of 114.4 ± 37.2 months, 59% of patients had persistently negative antibodies, while 25.7% of patients presented persistently positive aPL serology. Multivariate analysis confirmed that smoking (OR = 4; 95% CI: 1.45–11.08; p = 0.008) was an independent risk factor for positive persistence. Persistent positivity as well as a higher antibody load was associated with higher risk for further pregnancy morbidity. In 29 patients, with persistently negative serology who were asymptomatic, treatment with low-dose aspirin was discontinued. No clinical events related to APS were reported after treatment withdrawal, during the 40.95 months of follow-up.

Conclusions

A significant proportion of fertile women with aPL antibodies became negative during follow-up. Tobacco use and the number of positive antibodies are associated with persistently positive serology. Patients with persistently positive aPL serology suffer more obstetric complications. Treatment withdrawal might be safe in selected patients.

Section snippets

Study population

We conducted a retrospective study that included women attending the obstetric autoimmune pathology clinic of a tertiary facility serving a population of about 550,000 in Northern Spain. In this clinic, both gynecologist and rheumatologist attend pregnant women with either a previous diagnosis of an inflammatory condition or with history of pregnancy morbidities. These patients are tested for antiphospholipid antibodies as part of the routine diagnostic work-up. The women included were those

General characteristics of the study population

We reviewed the clinical charts of 309 patients attending the obstetric autoimmune pathology clinic, and finally included 105 female patients meeting inclusion criteria that had a confirmed positive aPL serology between October 1995 and December 2013. Median age at confirmed serological aPL positivity was 31.8 years (interquartile range: 28.9–36.2). Of the 105 patients included, 49 patients had pAPS (82% obstetric pAPS, 14% thrombotic pAPS, and 4% mixed pAPS), 42 patients had a positive

Discussion

There is a scarcity of information about the evolution of aPL serology and its associated factors as well as its consequences regarding thrombotic and obstetric events. We studied 105 female patients with a positive aPL serology who were attended in our autoimmune obstetric clinic. During almost 10 years of follow-up, only 25% remained persistently positive, and more than 50% became persistently negative. When analyzing possible factors implied, we identified tobacco use as an independent risk

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Cited by (17)

Deciphering the clinical significance of longitudinal antiphospholipid antibody titers
2024, Autoimmunity Reviews
In antiphospholipid syndrome (APS), the risk of clinical manifestations increases with higher titers of antiphospholipid antibodies (aPL). Despite the adoption of aPL titers in the classification approach to aPL-positive subjects, the value of longitudinal monitoring of those titers in the follow-up is still debated, being well studied only in systemic lupus erythematosus (SLE). The literature suggests that the rate of aPL positivity decreases during follow-up in primary APS, estimating that seroconversion occurs in between 8.9 and 59% of patients over time. Negativisation of aPL occurs more frequently in asymptomatic aPL carriers than in patients with full-blown APS as well as in subjects with single aPL positivity or low aPL antibody titers. In patients with SLE, aPL typically behave fluctuating from positive to negative and back again in the course of follow-up.
The few studies assessing the longitudinal course of aPL positivity with no associated systemic connective tissue disease reported a progressive decrement of aPL titers over time, in particular of antibodies against β2 glycoprotein I (antiβ2GPI) and cardiolipin (aCL) of IgG isotype. After a thrombotic event, aPL titers tend to decrease, as emerged from cohorts of both primary and secondary APS. Hydroxychloroquine has been identified as the most effective pharmacological agent to reduce aPL titers, with multiple studies demonstrating a parallel reduction in thrombosis rate. This review addresses available evidence on the significance of aPL titer fluctuation from clinical, therapeutic and pathogenic perspectives.
Persistence of antiphospholipid antibodies over time and its association with recurrence of clinical manifestations: A longitudinal study from a single centre
2022, Autoimmunity Reviews
Citation Excerpt :
Nevertheless, the mean follow-up time ranged between 1 and 3.5 years. A possible explanation for the lower rate of persistence in our population is that aPLs could tend to become negative during follow-up, as has been shown in up to 59% of women with positive aPLs [23]. This negativization seems to affect more frequently aCLs [10].
To analyze the antiphospholipid antibody (aPL) persistence over time in patients with antiphospholipid syndrome (APS) and its association with clinical recurrence and to identify predictors of aPL persistence over time.
200 patients with a diagnosis of APS and at least three follow-up aPL determinations were included. Persistent aPL profile was defined as the presence of lupus anticoagulant (LAC) and/or IgG/IgM anticardiolipin (aCL) and/or IgG/IgM anti-β2 glycoprotein-I (aβ2GPI) (> 99th percentile) antibodies in at least 66% of follow-up measurements. Multilevel mixed-effect generalized linear models with logit link were used.
112 (56%) patients maintained persistent aPL profiles over time, while 88 (44%) were transient. Median follow-up time was 172.5 months. Follow-up time did not affect the odds of aPL persistence in multivariate analysis (p = 1.00). Baseline triple aPL positivity [OR 78 (95%CI 16.9–359.7, p < 0.001)] and double aPL positivity [OR = 7.6 (95%CI 3.7–15.7, p < 0.001)] correlated with persistent aPLs over time, while isolated LAC [OR = 0.26 (95% CI 0.08–0.49, p = 0.002)] or isolated IgG/IgM aCL [OR = 0.20 (95% CI 0.11–0.59, p = 0.004)] positivity, were predictors of transient aPL profile. Patients with persistent aPLs had higher rate of clinical recurrence in comparison to patients with transient aPLs [OR = 2.48 (95%CI 1.34–4.58, p = 0.003)].
More than half of patients with baseline medium-high titer aPL positivity had persistent positive aPLs over time. Patients with persistent aPLs were more prone to present recurrence of clinical manifestations. Multiple aPL positivity increased the odds of a persistent aPL profile over time, while isolated LAC and aCL positivity decreased it.
Combined oral contraceptive-associated venous thromboembolism revealing an antiphospholipid syndrome: International retrospective study of outcomes.
2022, Thrombosis Research
Citation Excerpt :
Clinical evidence supports a link between aPLAbs and smoking [29]. Tobacco use favours persistently positive aPLAbs [30] and impacts on VTE risk in patients with aPLAbs [31]. The increased risk of recurrence in women with a proximal DVT or PE compared with a distal DVT is in line with published data [32,33]: proximal DVT was associated with a risk close to 3 % per year (1 event per 34.8 patient-years), as was PE (1 event per 38.9 patient-years).
Limitations in the data used to define thromboprophylaxis for patients with antiphospholipid antibodies (aPLAbs) and thrombosis include uncertainties after an initial provoked venous thromboembolic event (VTE). We aimed to study such cases associated with combined oral contraceptive (COC) intake.
We retrospectively analysed thrombotic outcomes after a first COC-associated VTE and positive aPLAbs, with a low risk HERDOO2 score, on low-dose aspirin (LDA) secondary thromboprophylaxis, seen from 2010 to 2021 in 3 tertiary referral centres, one in France and 2 in Russia. Data from 264 patients (distal deep vein thrombosis DVT: 62.9 %), cumulating in 1327.7 patient-years of observation, were collected.
There were 22 cases of thrombosis: 16 distal DVTs, 3 proximal, 1 pulmonary embolism (PE) and 2 transient ischemic attacks. Recurrence rate was 1.66 per 100 patient-years (p-y; 95 % CI: 0.96–2.33). No major bleeding occurred. Risk factors affecting recurrence-free survival were the time between first COC intake and VTE (p < 0.0001; the shortest, the lower), proximal DVT (p = 0.021), active smoking (p = 0.039), an associated systemic disease (p = 0.043) and circulating monocyte counts (p = 0.001).
We observed a low risk of recurrence which was modulated by classical risk factors for VTE. These observational data may provide clues for future randomized controlled trials.
Pregnancy and Systemic Lupus Erythematosus in Spain: Has Anything Changed in the 21st Century?
2022, Reumatologia Clinica
Analizar una cohorte de pacientes embarazadas con lupus eritematoso sistémico y comparar los desenlaces tanto de la enfermedad como del embarazo con los resultados de estudios previos realizados en la misma área geográfica.
Estudio de cohortes retrospectivo de 37 mujeres con lupus eritematoso sistémico (64 embarazos) seguidas en una consulta multidisciplinar. Estudio comparativo con los estudios españoles similares identificados tras revisión bibliográfica.
Nuestra cohorte se caracterizó por una edad más elevada y por la presencia de pacientes de origen no caucásico. Aunque no encontramos diferencias clínicas relevantes, serológicamente nuestra cohorte presentó una mayor frecuencia de anticuerpos antifosfolípido. Las pacientes incluidas en este estudio fueron tratadas más frecuentemente con antipalúdicos y aspirina. La frecuencia de brotes fue muy similar entre los distintos estudios, y no identificamos predictores claros para los mismos. Aunque la tasa de nacidos vivos fue similar, el desenlace obstétrico de nuestra serie fue mejor, con una baja tasa de preeclampsia, parto pretérmino y recién nacido de bajo peso. El único predictor de acontecimiento obstétrico adverso fue la edad.
Si bien los cambios en la actitud terapéutica y la planificación del embarazo no han tenido un impacto directo sobre la tasa de reactivación del lupus eritematoso sistémico durante el embarazo, sí que han supuesto una mejoría en los resultados obstétricos. La introducción de nuevas variables independientes de la enfermedad como la edad en la concepción, la procedencia sociocultural, o la disponibilidad de unidades multidisciplinares deberán ser consideradas en los resultados de próximos estudios.
To analyse a cohort of pregnant patients with systemic lupus erythematosus and compare the outcomes of both the disease and pregnancy with the results of previous studies conducted in the same geographical area.
Retrospective cohort study of 37 women with systemic lupus erythematosus (64 pregnancies) followed in a multidisciplinary unit. Comparative study with similar Spanish studies identified after literature search.
Our cohort was characterized by an older age and by the presence of non-Caucasian patients. Although we found no clinical differences, from the serological point of view our cohort presented a higher frequency of antiphospholipid antibodies. Patients included in this study were treated more frequently with antimalarials and low-dose aspirin. Systemic lupus erythematosus flare frequency was very similar between the different studies, and we did not identify clear predictors for them. Although the rate of live births was similar among studies, the obstetric outcome of our series was better with a very low rate of preeclampsia, preterm birth and low birth weight newborn. The only predictor of adverse obstetric event was age.
Although changes in the therapeutic attitude and planning of pregnancy in recent years have not had a direct impact on the rate of systemic lupus erythematosus flares during pregnancy, they have meant an improvement in the obstetric results. The introduction of new variables independent of the disease such as age at conception, socio-cultural origin, or the availability of multidisciplinary units should be considered in the results of future studies.
The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts’ Consensus
2021, Autoimmunity Reviews
Citation Excerpt :
After 26 months without treatment, she developed a new pulmonary embolism. The fourth study, led by Riancho-Zarrabeitia et al. [148], focused in 105 pregnant women with positive aPL, 49 of them had primary APS. Treatment was stopped in 13 women and no thrombotic events were observed after a median of 41 (9-135) months.
Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure.
Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events.
In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients.
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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¹: These authors have equally contributed to this article and shared first authorship.

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Serological evolution in women with positive antiphospholipid antibodies

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Study population

General characteristics of the study population

Discussion

J Thromb Haemost

Rev Clin Esp

J Thromb Haemost

Autoimmun Rev

Semin Arthritis Rheum

Antiphospholipid syndrome: an update

Eur J Clin Invest

Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review

Rheumatology (Oxford)

Transient antiphospholipid syndrome associated with primary cytomegalovirus infection: a case report and literature review

Case Rep Rheumatol

Transient antiphospholipid antibodies associated with acute infections in children: a report of three cases and a review of the literature

Eur J Pediatr

Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus