Avoiding misclassification of thrombotic primary antiphospholipid syndrome as systemic lupus erythematosus (SLE): What are the best-performing SLE classification criteria?

BACKGROUND: Systemic lupus erythematosus (SLE) and Primary Antiphospholipid Syndrome (PAPS) overlap clinical and immunological features. Therefore, misclassification of PAPS patients as SLE is a concern. The ACR/EULAR 2019 SLE classification has never been studied in PAPS. OBJECTIVE: To verify if the ACR/EULAR 2019 SLE classification can correctly classify a PAPS patient as not having SLE and compare its performance with the SLICC 2012 SLE classification. Methods: One-hundred thrombotic PAPS patients who fulfilled the Sidney criteria were consecutively screened and those who attended the inclusion criteria were submitted to ACR/EULAR 2019 and SLICC 2012 classifications. RESULTS: Sixty-seven PAPS patients were included in this study. The majority was female (89.6%) with median age at study inclusion of 45 years (35-53) and median PAPS disease duration of 13 years (8-19). PAPS correct classification was observed more often with ACR/EULAR 2019 than SLICC 2021 criteria (94.0% vs. 64.2%; p < 0.001). The 4 misclassified patients in ACR/EULAR 2019 were also misclassified in SLICC 2012. The comparison of misclassified patients to those correctly not classified as SLE resulted, for both criteria, in higher frequencies of hematological domain [ACR/EULAR 2019 (100% vs. 28.6%, p = 0.010) and SLICC 2012 (95.8% vs. 11.6%, p < 0.001)]. Further analysis of hematological manifestations revealed that for the ACR/EULAR 2019 leukopenia (100% vs. 22.2%, p = 0.004) and for the SLICC 2012 leukopenia/lymphopenia (91.7% vs. 7%, p < 0.001) were more frequent in misclassified group. Proteinuria (20.8% vs. 0%, p = 0.004) and low complement (45.8% vs. 20.9%, p = 0.033) were also more often observed in the incorrectly SLICC 2012 classified patients. CONCLUSION: ACR/EULAR 2019 had high accuracy for distinguishing PAPS from SLE, whereas the SLICC 2012 incorrectly classified more than one third of the PAPS patients as having SLE.

Development of a New International Antiphospholipid Syndrome Classification Criteria Phase I/II Report: Generation and Reduction of Candidate Criteria.

OBJECTIVE: An international multidisciplinary initiative, jointly supported by the American College of Rheumatology and European Alliance of Associations for Rheumatology, is underway to develop new rigorous classification criteria to identify patients with high likelihood of antiphospholipid syndrome (APS) for research purposes. The present study was undertaken to apply an evidence- and consensus-based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains. METHODS: During phase I, the APS classification criteria steering committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains. RESULTS: Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in phase II, we initially reduced these items to 64 potential candidate criteria organized into 10 clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into 6 additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification. CONCLUSION: Using data- and consensus-driven methodology, we identified 27 APS candidate criteria in 6 clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real-world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification.

A glimpse into the history of description of the antiphospholipid syndrome.

Prior to 1983, several landmark reports prepared the stage for a detailed description of the Antiphospholipid (Hughes) syndrome (APS). Formerly depicted as lupus-like, APS exhibits a wide spectrum of symptoms that overlap with Sjogren's, Hashimoto, and other autoimmune diseases. In this review, we take a glimpse into the history of description of APS, discussing the events that led to its recognition as one of the most common autoimmune diseases and the enormous impact of that recognition in the rheumatology field.

Recomendaciones de la Sociedad Española de Reumatología sobre síndrome antifosfolípido primario. Parte I: diagnóstico, evaluación y tratamiento / Recommendations of the Spanish Rheumatology Society for primary antiphospholipid syndrome. Part I: diagnosis, evaluation and treatment

OBJETIVO: 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. MÉTODOS: 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». RESULTADOS: 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. CONCLUSIONES: 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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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

Direct oral anticoagulants in patients with antiphospholipid syndrome: a cohort study.

OBJECTIVES: Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients. PATIENTS AND METHODS: In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB). RESULTS: APS patients were followed for a median time of 51 (interquartile range 43-63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54-10.28, p = 0.004 and HR = 3.69, 95% CI: 1.27-10.68, p = 0.016, respectively) with no differences between rivaroxaban and apixaban or single- or double-positive and triple-positive APS. Thromboembolism on DOACs was associated with older age (median 52 versus 42 years, p = 0.008) and higher global APS score (median 13 versus 8.5, p = 0.013). Patients on DOACs had increased risk of major bleeding or CRNMB (HR = 3.63, 95% CI: 1.53-8.63, p = 0.003), but rates of gastrointestinal bleeds (HR = 3.36, 95% CI: 0.70-16.16, p = 0.13) and major bleeds or CRNMB other than heavy menstrual bleeding (HR = 2.45, 95% CI: 0.62-9.69, p = 0.2) were similar in both treatment groups. CONCLUSION: During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

Improvements in diagnosis and risk assessment of primary and secondary antiphospholipid syndrome.

Classification criteria for antiphospholipid syndrome have not been updated since the revised Sapporo classification criteria were published in 2006. These criteria have limitations in that they omit nonclassical manifestations (hematologic and neurologic), include anticardiolipin and anti-ß2-glycoprotein I immunoglobulin (Ig)M isotypes, and do not separately consider primary (no autoimmune disease) or secondary (usually systemic lupus erythematosus) disease. Recent findings in antiphospholipid antibody include fluctuation of antiphospholipid antibodies, recognition that IgA isotypes do confer risk, identification of the role of complementopathy in catastrophic antiphospholipid syndrome, and elucidation of the role of thrombosis risk equations.

Laboratory Evaluation of Antiphospholipid Syndrome.

OBJECTIVES: Anti-ß2 glycoprotein I domain I (anti-domain I) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are present in patients with antiphospholipid syndrome (APS); however, their use in evaluation remains unclear. METHODS: Diagnostic attributes of lupus anticoagulant (LAC), anti-domain I IgG, anti-cardiolipin, anti-ß2 glycoprotein I (anti-ß2GPI), and aPS/PT IgG and IgM antibodies were assessed in 216 patients evaluated for APS. RESULTS: LAC had the best odds ratio (OR, 14.2) while that for anti-domain 1 IgG was comparable to anti-ß2GPI IgG (OR, 8.3 vs 9.4) but higher than all others. Significant correlations were observed for thrombosis (P = .03) and pregnancy-related morbidity (P = .001) with anti-domain IgG and for any thrombosis with aPS/PT IgG (P = .006). Use of noncriteria antiphospholipid with or without criteria markers did not significantly increase the probability to diagnose APS. CONCLUSIONS: Noncriteria tests can contribute to diagnosis and stratification of APS but do not improve diagnostic yield. Optimal strategies for implementation require prospective investigation.

The clinical value of assays detecting antibodies against domain I of ß2-glycoprotein I in the antiphospholipid syndrome.

As the clinical symptoms of the antiphospholipid syndrome (APS) frequently occur irrespective of the syndrome, diagnosis predominantly depends on the laboratory assays measuring the level or function of antiphospholipid antibodies (aPLs). ß2-glycoprotein I (ß2GPI) is increasingly accepted as the most important target of aPLs. Anti-ß2GPI antibodies constitute a heterogeneous population, but current in vivo and in vitro evidence show that especially the first domain (DI) of ß2GPI contains an important pathogenic epitope. This epitope containing Glycine40-Arginine43 (G40-R43) has proven to be cryptic and only exposed when ß2GPI is in its open conformation. A previous study demonstrated a highly variable exposure of the cryptic epitope in commercial anti-ß2GPI assays, with implications on correct patient classification. Unexpectedly, recent unpublished data revealed impaired exposure of the pathogenic epitope in the commercially available anti-DI chemiluminescence immunoassay (CIA) assay detecting specific antibodies directed to DI. In this review we summarize the laboratory and clinical performance characteristics of the different anti-DI assays in published data and conclude with inconsistent results for both the correlation of anti-DI antibodies with clinical symptoms and the added value of anti-DI antibodies in the classification criteria of APS. Additionally, we hypothesize on possible explanations for the observed discrepancies. Finally, we highly advise manufacturers to use normal pooled plasma spiked with the monoclonal anti-DI antibodies to verify correct exposure of the cryptic epitope.

Classification of primary antiphospholipid syndrome as systemic lupus erythematosus: Analysis of a cohort of 214 patients.

OBJECTIVES: To assess the limitations of the SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for systemic lupus erythematosus (SLE), in patients with primary antiphospholipid syndrome (PAPS). METHODS: Retrospective study of a cohort of APS patients (Sydney criteria). We successively excluded patients with (1) at least one "SLE-specific" manifestation (biopsy-proven SLE nephropathy, arthritis, cutaneous, or neurologic SLE manifestations, pericarditis, autoimmune haemolytic anaemia, oral and nasal ulcers, non-scarring alopecia, anti-dsDNA, and anti-Sm antibodies), (2) any other autoimmune connective tissue disease, and/or (3) antinuclear antibodies >1/320. Careful file review confirmed PAPS among the remaining patients. We then assessed the number of SLICC criteria each patient met. RESULTS: Among these 214 APS patients, we excluded 85 with at least one SLE-specific manifestation, 8 with another connective tissue disease, and 21 with antinuclear antibodies >1/320, leaving 100 patients with primary APS. Among them, 28% met at least 4 SLICC classification criteria including one clinical and one immunological criterion (antiphospholipid antibodies, aPL, by definition) and could thus theoretically be classified with SLE. Fourteen had an arterial phenotype (50%), 9 a history of catastrophic APS (32%), and 18 a triple-positive profile for aPL (64%). None had developed SLE during a median follow-up of 12 [6.5-17] years. CONCLUSION: Because 28% of our patients with longstanding and strictly defined PAPS could be mistakenly classified as SLE, they were at risk of deleterious therapeutic management. We therefore suggest that any future classification for SLE should specifically require at least one SLE-specific criterion for patients with aPL.

Prevalence, persistence and clinical correlations of classic and novel antiphospholipid antibodies in systemic lupus erythematosus.

Objectives: aPL are frequently present in SLE. In a well characterized SLE cohort we aimed at investigating the prevalence of aPL and assessing their analytical performance and clinical association by testing criteria specificities including LA, aCL IgG and IgM, anti-ß2-glycoprotein 1 (antiß2GP1) IgG and IgM, as well as the non-criteria aPS-PT IgG and IgM and anti-ß2GP1 domain 1 (aD1) IgG. Methods: We included 178 patients satisfying the ACR SLE classification criteria, from whom 283 samples and thrombotic events were collected longitudinally. Each sample was tested for criteria and non-criteria aPL using validated techniques in a single centre. Results: All assays provided highly reproducible results. Of the samples, 42.5% were positive for at least one criteria assay, 20.5% showed double positivity and 12.6% triple positivity. All criteria and non-criteria specificities persisted over time. Most antibody titres were only moderately correlated; however, strong correlation was observed on one hand between aD1 IgG, antiß2GP1 IgG and aCL IgG, and on the other between aPS-PT IgG and LA. aD1 IgG titres were extremely elevated in triple-positive samples. aPS-PT IgG by itself, and jointly with LA, was associated with thrombosis, an association mostly driven by venous thrombotic events. Conclusions: In this SLE cohort, the non-criteria aPL aD1 IgG and aPS-PT IgG performed differently. aD1 IgG was highly enriched in triple-positive samples, and aPS-PT IgG, jointly with LA, was associated with thrombotic events.

Catastrophic antiphospholipid syndrome (Ronald Asherson syndrome) and obstetric pathology.

BACKGROUND: Catastrophic antiphospholipid syndrome (CAPS) is an uncommon, often fatal, variant of the antiphospholipid syndrome (APS) that results in a widespread coagulopathy and high titres of antiphospholipid antibodies (aPL) and affects predominantly small vessels supplying organs with the development of multiorgan failure. It remains unclear why some patients develop the typical clinical picture of APS (thrombosis of large vessels), whereas others show the development of progressive microthrombosis, which the authors called "thrombotic storm" and multiple organ failure, that is, CAPS. MATERIALS AND METHODS: Since 2001-2016, we discovered 17 patients with CAPS development. CONCLUSION: CAPS is life-threatening condition, but optimal treatment for CAPS is not developed yet and the mortality rate is as high as 30%-40%.

Antiphospholipid syndrome (APS) revisited: Would migraine headaches be included in future classification criteria?

Headaches have been extensively reported in Antiphospholipid syndrome (APS)/Antiphospholipid antibodies (aPL)-positive patients. The aim of this study was to highlight the prevalence of headaches among APS/aPL-positive patients and discuss its association with laboratory, clinical and imaging findings. We searched the literature through Google Scholar and PubMed for publications on the epidemiology, pathogenesis, laboratory, imaging and clinical findings, and management of headaches in APS/aPL-positive patients. The following keywords were used: Antiphospholipid, Hughes syndrome, anticardiolipin, lupus anticoagulant, anti-ß2 glycoprotein I, headache, migraine, tension, and cluster. All reports published between 1969 and 2015 were included. Migraine is the most commonly reported type of headache in APS/aPL-positive patients. Thrombotic and platelet dysfunction hypotheses have been studied to uncover the pathogenic role of aPL in the development of headaches. Several studies are reporting higher levels of aPL in primary and secondary APS migraineurs, but only few reached statistical significance. Migraine patients without clinical signs/symptoms of cerebral infarction rarely show positive imaging findings. Digital subtraction angiography shows promise in demonstrating small vascular lesions otherwise not detected on computed tomography, magnetic resonance imaging, or cerebral angiograms. Although it may be solitary and harmless in many cases, the deleterious effect of migraine on the quality of life of APS patients prompts rapid diagnosis and proper management. An anticoagulation trial is advisable in APS patients with migraine as many cases of severe, refractory migraine resolved with anticoagulation therapy. The profile of migraine headaches discussed in this study permits its candidacy for inclusion in future APS classification criteria.

Diagnóstico en el síndrome antifosfolipídico: desde una perspectiva histórica a la aparición de nuevos autoanticuerpos / Diagnosis of antiphospholipid syndrome: From an historical perspective to the emergence of new autoantibodies

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[Antiphospholipid syndrome and pregnancy]. / Antifosfolipidsyndrom og graviditet.

Antiphospholipid syndrome (APS) is the association of antiphospholipid antibodies with thromboses and/or obstetric morbidity. Obstetric morbidity includes recurrent first trimester loss, stillbirth, intrauterine death, preeclam-psia, premature birth and fetal growth restriction. Although current treatment regimens including aspirin and low-molecular weight heparin have improved pregnancy outcomes, 30% of affected women have pregnancy complica-tions. Women with APS are therefore high-risk pregnancies who should be monitored in specialist centres according to international standards.

[Pathogenesis and Laboratory Findings in Antiphospholipid Syndrome, Especially Associated with Lupus Anticoagulant].

Antiphospholipid syndrome (APS), an acquired thrombotic condition, is a complex clinical state characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Revised APS classification criteria are used for diagnosis, which include at least one clinical criterion (thrombosis or pregnancy loss) and at least one of the laboratory criteria [anticardiolipin antibodies, anti-ß2GPI antibodies, lupus anticoagulant (LA)]. LA is also an independent risk factor for developing thrombosis, though some LA-positive cases have been reported to have a bleeding symptom. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disorder characterized by a bleeding tendency due to low prothrombin activity in patients with LA, and has recently been reported not only in children but also in adults We have encountered LA cases with bleeding and low coagulation factor activities except for prothrombin. Based on our findings, we propose that LA-positive cases with a bleeding symptom and characterized by low coagulation factor activity including prothrombin be termed lupus anticoagulant-associated coagulopathy (LAAC). Furthermore, coagulation factor autoantibodies are often detected in LAAC patients; thus, correct measurement of LA is important to distinguish LAAC patients from those possessing an inhibitor to coagulation factors such as acquired hemophilia A as well as to select the optimal therapeutic strategy.

[Antiphospholipid syndrome and pregnancy: Obstetrical prognosis according to the type of APS]. / Syndrome des anticorps antiphospholipides et grossesse : pronostic obstétrical selon le type de SAPL.

OBJECTIVE: The objective of our study was to compare treatment-based obstetrical outcomes in women with either thrombotic or obstetrical antiphospholipid syndrome (APS). MATERIALS AND METHODS: This was a historical cohort study conducted between 1998 and 2009 in 23 patients who had a total of 83 pregnancies. The syndrome was diagnosed using the 2006 Sapporo criteria. RESULTS: Thirty-one of these 83 pregnancies were valid before the diagnosis was made. A live infant was born in 22% of them, the infant being small for gestational age in 26% of cases. The fetus died in utero in a further 26% of cases. Pregnancies were subdivided into 2 groups depending on whether the initial event leading to APS diagnosis was obstetrical or thrombotic. Treatment (aspirin and low molecular weight heparin) was based on this classification: the latter was given in a curative dose for thrombotic events, in a preventive dose for obstetrical events. No fetal loss was observed when treatment was administered according to the protocol. Nevertheless, 20% of the pregnancies with obstetrical APS were complicated by smallness for gestational age and only 38% of the infants were live births. More than 87% of the thrombotic forms treated were free of complications and led to birth of a living child. CONCLUSION: Appropriate treatment appears to improve the prognosis for pregnancies in patients with APS. These patients are nevertheless at increased risk of an obstetrical event and require close monitoring, especially in obstetrical manifestations, which appear to have a poorer prognosis. Multidisciplinary follow-up by an experienced team is essential.

Recurrent miscarriages in women not fulfilling classification criteria for antiphospholipid antibody syndrome.

Obstetric antiphospholipid antibody syndrome (APS), is well defined by classification criteria. It is well known that women with APS should receive prophylactic anticoagulation therapy with subcutaneous low weight heparin all throughout pregnancy and in the first 6 weeks postpartum. However, the optimal treatment for pregnant women having positive anti-phospholipid antibodies, but not fulfilling classification criteria for APS is still unclear. In this retrospective study we report pregnancy outcomes of 10 patients affected by recurrent miscarriages and positive anti-cardiolipin or aß2GP1 antibodies with titers ranging from 10 to 20 GPL/MPL demonstrated at least twice before pregnancy.

Catastrophic antiphospholipid syndrome: task force report summary.

The Task Force on Catastrophic Antiphospholipid Syndrome (CAPS) aimed to assess the current knowledge on pathogenesis, clinical and laboratory features, diagnosis and classification, precipitating factors and treatment of CAPS. This article summarizes the main aspects of its final report.

Antiphospholipid antibody testing for the antiphospholipid syndrome: a comprehensive practical review including a synopsis of challenges and recent guidelines.

The antiphospholipid (antibody) syndrome (APS) is an autoimmune condition characterised by a wide range of clinical features, but primarily identified as thrombotic and/or obstetric related adverse events. APS is associated with the presence of antiphospholipid antibodies (aPL), including the so-called lupus anticoagulant (LA). These aPL are heterogeneous in nature, detected with varying sensitivity and specificity by a diverse range of laboratory tests. All these tests are unfortunately imperfect, suffer from poor assay reproducibility (inter-method and inter-laboratory) and a lack of standardisation and harmonisation. Clinicians and laboratory personnel may struggle to keep abreast of these factors, as well as the expanding range of available aPL tests, and consequent result interpretation. Therefore, APS remains a significant diagnostic challenge for many clinicians across a wide range of clinical specialities, due to these issues related to laboratory testing as well as the ever-expanding range of reported clinical manifestations. This review is primarily focussed on issues related to laboratory testing for APS in regards to the currently available assays, and summarises recent international consensus guidelines for aPL testing, both for the liquid phase functional LA assays and the solid phase assays (anticardiolipin and anti-beta-2-Glycoprotein-I).