Acute Renal Thrombotic Microangiopathy Caused by Eltrombopag and Romiplostim in a Patient with Myelodysplastic Syndromes (MDS) and Underlying Antiphospholipid Syndrome.

Romiplostim and eltrombopag are synthetic agonists of the thrombopoietin receptor (TPO-R), commonly used for immune thrombocytopenic purpura (ITP) and sometimes in myelodysplastic syndrome (MDS). They are rarely associated with kidney injury. We report a case of acute kidney injury caused by romiplostim and eltrombopag in an 80-year-old male patient with MDS and ITP. He did not have systemic haemolysis syndrome but isolated acute renal thrombotic microangiopathy confirmed by kidney biopsy. He was treated with steroids, plasmapheresis and anticoagulation, with improvement in renal function. Interestingly, the patient had high antiphospholipid (aPL) antibodies noted upon screening, indicating a possible new antiphospholipid syndrome (APS) diagnosis. In the presence of circulating aPL antibodies, eltrombopag may have served as a trigger, causing endothelial injury and subsequent renal microangiopathy; aPL antibodies were still significantly positive at four weeks of outpatient testing. This case and a few others reported in the literature highlight the importance of screening for aPL antibodies before initiating TPO-R agonists in patients with ITP. We suspect that using TPO-R agonists, rather than underlying aPL, caused renal failure. LEARNING POINTS: Synthetic agonists of the thrombopoietin receptor, such as romiplostim or eltrombopag, can cause acute renal failure.Preexisting antiphospholipid (aPL) antibodies may increase the risk of renal failure.Screening for aPL antibodies should be considered before initiating thrombopoietin-receptor agonists (TPO-R agonists) in patients with immune thrombocytopenic purpura (ITP).

Comparative assessment of the diagnostic performances of particle-based multianalyte technology and commercial ELISA for antiphospholipid autoantibody testing.

BACKGROUND: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-ß2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes. METHODS: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT's performance was evaluated against commercial ELISA in detecting aPL antibodies. RESULTS: At the manufacturer's suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88-90% specificity), IgA and IgM antibodies yielded 5.9-17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity. CONCLUSIONS: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation.

[Beyond hypercoagulability in celiac disease]. / Más allá de la hipercoagulabilidad en la enfermedad celíaca.

In celiac disease (CD) there is a state of hypercoagulability and multiple factors have been found that may be involved. Cases of association of CD and antiphospholipid síndrome (APS) have been described and several observational studies have found an increase in antiphospolipid antibodies (AAF) in patients with CD, so both entities may be interrelated, increasing the risk of thrombotic events. A descriptive case of a patient who is simultaneusly diagnosed with CD and APS is presented.

A Comparison of Obstetric Outcomes in Antiphospholipid Syndrome Among Pregnant Women With Systemic Lupus Erythematosus.

Objective The aim of this study was to evaluate the maternal and perinatal outcomes in systemic lupus erythematosus (SLE) women with antiphospholipid syndrome (APS). Methods This retrospective case-control study was conducted among pregnant women with SLE with and without APS. Group A included SLE patients with APS, whereas group B included pregnant SLE women without APS. Data were expressed as mean ± standard deviation (SD). Frequency and percentage were computed for categorical data. The chi-square test was used to analyze the difference between categorical data. Results Out of 125 cases of SLE, APS was found in 72 (57.6%) women. Almost 95.8% of patients were on treatment (aspirin and enoxaparin) in group A. Preterm delivery (31.89±7.36 versus 34.46±4.97; p=0.021) and termination of pregnancy (18.1% [13/72] versus 5.7% [3/53]; p=0.04) were statistically significant in group A. Among these terminations, second-trimester intrauterine death is found to be more in group A (SLE with APS) (16.7% [12/72]) as compared to group B (SLE without APS) (5.7% [3/53]) with a p-value of 0.05. Perinatal outcomes including NICU admissions (39% [23/59] versus 24% [12/50]; p=0.071) and neonatal death (12.3% [7/57]; p=0.015) were also found to be statistically significant between the two groups. Conclusion APS with SLE is associated with adverse pregnancy outcomes such as preterm birth, termination of pregnancy due to second-trimester fetal loss, more NICU admission, and neonatal deaths when compared to the control group. Hence, pregnancies with APS with SLE require vigilant monitoring and frequent follow-ups to ensure a positive pregnancy outcome.

The association between antiphospholipid syndrome and atrial fibrillation: a single center retrospective case-control study.

Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim of this study is to investigate the association between APS and atrial fibrillation (AF) among patients in Peking University People's Hospital. A single center retrospective study was conducted. Cases were hospitalized patients diagnosed with AF by a cardiologist while the control group patients did not exhibit cardiac diseases. The results of the study revealed that in multivariable logistic regression, APS, anticardiolipin antibody (aCL) positivity and anti-beta-2-glycoprotein antibody (anti-ß2GPI) positivity are independent risk factors of AF. APS, aCL positivity and anti-ß 2GPI positivity are statistically different between AF patients and non-AF patients. Forthcoming studies are needed to clarify the potential link between APS and AF.

[Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues]. / 产科抗磷脂综合征的诊治原则与热点问题述评.

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

The relevance of antiphospholipid antibodies in obstetrics.

AIM AND METHODOLOGY: To provide a comprehensive review on new findings and current recommendations regarding antiphospholipid antibodies with particular emphasis on clinical impact on gestation. CONCLUSION: Antiphospholipid antibodies are an important risk factor for the development of a series of pregnancy-related complications. Early diagnosis and appropriate therapy can reduce the incidence of pregnancy loss and pregnancy-related complications.

Antiphospholipid Syndrome and Patent Foramen Ovale: A Case Report and Literature Review.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or non-thrombotic manifestations in patients with persistent antiphospholipid antibodies (aPL). Catastrophic APS is a rare and severe form of APS that is defined by the presence of multiple vascular occlusive events. When a patent foramen ovale (PFO) is present, paradoxical embolization can occur, simultaneously leading to arterial and venous thrombosis. We present a complex clinical case of a patient who presented with multiple arterial and venous thrombotic events with positive aPL. The suspicion of catastrophic APS was removed when a PFO was found in a transesophageal echocardiogram, justifying paradoxical embolization. This emphasizes the importance of searching for PFO in patients with APS presenting with simultaneous venous and arterial thrombosis for management and prognosis purposes.

Crossed-reflex in antiphospholipid chorea.

Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases.

The Relentless Recurrence of Diffuse Alveolar Hemorrhage in Catastrophic Antiphospholipid Syndrome and Lupus: A Therapeutic Challenge.

Diffuse alveolar hemorrhage (DAH), a rare complication of coexisting antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE), poses significant diagnostic and therapeutic challenges, especially with recurrent episodes. We present a 27-year-old male with catastrophic APS and SLE who experienced acute respiratory failure and hemoptysis due to DAH. Despite aggressive therapy with immunosuppressants, plasma exchange, and anticoagulation, he had recurrent DAH episodes requiring repeated admissions. Early recognition, multidisciplinary management, and utilization of effective targeted therapies, such as intravenous immunoglobulin, in refractory cases are crucial for improving outcomes in this challenging complication.

Antiphospholipid antibodies in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by recurrent pregnancy morbidity or thrombosis in combination with the persistent presence of antiphospholipid antibodies (aPLs) in plasma/serum. Antiphospholipid antibodies are a heterogeneous, overlapping group of autoantibodies, of which anti-ß2-glycoprotein I (aß2GPI), anticardiolipin (aCL) antibodies and antibodies that prolong plasma clotting time in tests in vitro known as lupus anticoagulant (LAC) are included in the laboratory criteria for the diagnosis of APS. The presence of LAC antibodies in plasma is indirectly determined by measuring the length of coagulation in two tests - activated partial thromboplastin time (aPTT) and diluted Russell's viper venom time (dRVVT). The concentration of aß2GPI and aCL (immunglobulin G (IgG) and immunoglobulin M (IgM) isotypes) in serum is directly determined by solid-phase immunoassays, either by enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay (FIA), immunochemiluminescence (CLIA) or multiplex flow immunoassay (MFIA). For patient safety, it is extremely important to control all three phases of laboratory testing, i.e. preanalytical, analytical and postanalytical phase. Specialists in laboratory medicine must be aware of interferences in all three phases of laboratory testing, in order to minimize these interferences. The aim of this review was to show the current pathophysiological aspects of APS, the importance of determining aPLs-a in plasma/serum, with an emphasis on possible interferences that should be taken into account when interpreting laboratory findings.

Exploring the impact of acute viral exposure on clinical characteristics and antibody profiles in antiphospholipid syndrome: a study in CAPSTONE.

The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.

Impact of Inherited Thrombophilia in Women with Obstetric Antiphospholipid Syndrome: A Single-Center Study and Literature Review.

Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the presence of antiphospholipid syndrome (APS). The aim of this study was to assess the prevalence and impact of IT on fetal-maternal outcomes and thrombotic risk in women within the spectrum of obstetric APS. Three hundred and twenty-eight women with APS-related obstetric morbidity ever pregnant were included. Of these, 74 met the APS classification criteria, 169 were non-criteria (NC)-APS, and 85 were seronegative (SN)-APS. Patients with other autoimmune diseases were excluded. APOs included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. Successful pregnancy was defined as the achievement of a live newborn. A literature search was also performed. The mean age of the overall group was 33.9 ± 5.3 years, and the patients were followed up for 35 (11-79) months. During the study period, there were 1332 pregnancies. Nearly 14% of the patients had an associated IT. IT patients more frequently received the standard-of-care (SoC) therapy. The presence of IT was not associated with worse maternal-fetal outcomes in patients treated with SoC treatment. Overall, IT patients had a lower frequency of newborns without treatment, especially those without definite APS. In addition, IT did not increase the risk of thrombosis during pregnancy or the postpartum period. A detailed analysis of the literature review identified only four publications related to our study and did not show conclusive evidence of the impact of IT on patients with obstetric APS. The group of women with APS-related obstetric morbidity and IT who did not receive treatment, especially those without definite APS, had a worse prognosis in terms of a live birth. However, with SoC therapy, the prognosis is similar in those patients without IT. The association of IT with APS does not seem to predispose to the development of thrombosis during pregnancy and/or the postpartum period.

Bulk T-cell receptor sequencing confirms clonality in obstetric antiphospholipid syndrome and may as a potential biomarker.

The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRß repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.

Domain 5 of Beta 2 glycoprotein I: Friend or foe in health? Context matters.

Beta 2 glycoprotein I (ß2GPI) is the major autoantigen in the antiphospholipid syndrome, an autoimmune disorder characterized by thrombotic and obstetric complications. The autoantibodies that target beta 2 glycoprotein I are pathogenic and contribute to disease pathogenesis. The ß2GPI molecule is composed of 5 domains that are numbered 1 through to 5. Autoantibodies bind mainly to domain 1 whereas the majority of the biological functions of the ß2GPI molecule in diverse processes such as apoptotic cell clearance, complement regulation, lipopolysaccharide clearance and anticoagulation have been localised to domain 5 and its unique biochemistry, reviewed in this article. The role of purified domain 5 peptide as a potential therapeutic agent in APS and ischemia reperfusion injury is discussed.

Extensive Thrombosis in Catastrophic Antiphospholipid Syndrome in a Newly Diagnosed Systemic Lupus Erythematosus: A Case Report.

In this case report, we present the development of catastrophic antiphospholipid syndrome (CAPS), a rare and potentially fatal consequence of systemic lupus erythematosus (SLE), in a 33-year-old Micronesian woman. CAPS is characterized by extensive arterial thrombosis and multiorgan failure. The patient first showed signs of neuropsychiatric symptoms, brain infarctions on imaging, and severe hypoxic respiratory failure brought into the hospital by diffuse alveolar hemorrhage (DAH) along with lupus nephritis (LN). Blood urea nitrogen (BUN) and creatinine (Cr) were progressively elevated to 102/4.1 mg/dL, respectively. A urinalysis revealed microscopic hematuria and proteinuria with a urine protein/creatinine ratio of 6052 mg/g. She was also found to have had microangiopathic hemolytic anemia (MAHA) and severe venous thrombosis, both of which were indicative of CAPS. An aggressive approach, including immunosuppressive medication, therapeutic plasma exchange, and anticoagulation, had positive results, including renal recovery and the cessation of thrombotic episodes. This instance highlights how crucial it is to identify CAPS patients early and take appropriate action to improve patient outcomes for this difficult and sometimes deadly disorder.

Antiphospholipid Syndrome and Antibodies Associated With Malignancy and Older Age: A Retrospective Study.

BACKGROUND: Antiphospholipid syndrome (APLS) is an established cause of thrombosis and hypercoagulability. However, the clinical characteristics of those with APLS or patients with positive antiphospholipid antibodies (APLA) in the embolic stroke of undetermined source (ESUS) have not been well studied. METHODS: A retrospective analysis was conducted between January 1, 2010, and December 31, 2020, across all three Mayo Clinic sites. Patients who were included in the study were tested for APLA and had a diagnosis of ESUS. Baseline characteristics, radiographic parameters, and outcome data were collected and compared between those who tested positive for APLS or had positive APLA and those who were negative. RESULTS: A total of 206 patients were included in the study. Eight (4%) patients were diagnosed with APLS, and 21 (10%) patients had positive APLA. On comparing those with a diagnosis of APLS and those without, patients with APLS were found to be significantly older (75 years old ± 9 vs. 58 years old ± 14, p = 0.001) and were more likely to have a history of cancer (50% vs. 13%, p = 0.012). Those with positive APLA had similar findings of being older (67 years old ±13 vs. 58 years old ± 14 p = 0.003) and more likely to have a history of cancer (29% vs. 8.4% p = 0.027). Radiographically, those with APLS had a higher white matter disease burden (Fazekas score median 2 (IQR 1.5-3) vs. median 1 (IQR 1-2), p = 0.028). CONCLUSION: Both APLS and positive APLA are associated with older age and a history of malignancy. These findings highlight the importance of considering a hypercoagulable evaluation even in the elderly ESUS population.

Neuromyelitis optica spectrum disorder co-existing with antiphospholipid syndrome: A case report.

Key clinical message: Neuromyelitis optica spectrum disorder is an autoimmune disease, rarely presents with antiphospholipid syndrome. Diagnosis and management of NMOSD are challenging in the background of diverse presentations, especially in resource-limited settings. Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is a progressive demyelinating autoimmune condition resulting from the autoantibodies produced against aquaporin-4 (AQP-4) proteins which are widely distributed in astrocytes in the nervous system. In the setting of NMOSD, it is very crucial to consider other autoimmune diseases as differential diagnoses or co-occurrences due to the diversity of symptoms. NMOSD co-exists with other autoimmune diseases such as myasthenia gravis, thyroid disease, ankylosing spondylitis, pernicious anemia, thrombotic thrombocytopenic purpura, ulcerative colitis, and systemic lupus erythematosus. Few cases of antiphospholipid syndrome co-existing with NMOSD have been reported. In resource-limited settings, the published data are scarce, and therefore, autoimmune diseases are poorly studied. Therefore, late diagnosis and delayed treatment initiation pose long-term sequelae and hence poor prognosis. Here, we present a case of an African woman in her early 40s presenting with bilateral progressive loss of vision, transverse myelitis, extensive longitudinal hyperintense T2 cervical lesion, and AQP-4 autoantibody keeping with NMOSD. The co-existence of antiphospholipid syndrome, in this case, was supported by a history of recurrent pregnancy loss and positive antiphospholipid antibodies. This case underscores the importance of individualized-based medicine, especially in resource-limited settings.

Toward harmonized interpretation of anticardiolipin and anti-ß2-glycoprotein I antibody detection for diagnosis of antiphospholipid syndrome using defined level intervals and likelihood ratios: communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

BACKGROUND: Improving harmonization of the clinical interpretation of anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies immunoglobulin G (IgG)/immunoglobulin M (IgM) in the diagnosis of antiphospholipid syndrome (APS) is desirable. Likelihood ratios (LRs) with corresponding test-result intervals can identify the power of a test to discriminate between a diseased and nondiseased patient and may be useful for the semiquantitative interpretation of aCL/aß2GPI results. OBJECTIVES: To determine moderate and high thresholds for aCL and aß2GPI IgG/IgM measured with chemiluminescent immunoassay, enzyme-linked immunosorbent assay, fluorescence enzyme immunoassay, and multiplex flow immunoassay. METHODS: aCL and aß2GPI antibodies IgG/IgM were determined with 4 solid-phase systems in a case-control study population including 381 APS patients and 727 controls. Interval-specific LRs (IS-LR) were calculated for ranges determined by prespecified specificity and sensitivity levels. Three methods were used for determining thresholds that separated low, moderate, and high positive antibody levels. Interassay agreement was checked with Cohen's kappa statistics. RESULTS: Assay- and antibody-specific thresholds demonstrated increasing IS-LR, reflecting different clinical significance for low, moderate, and high levels, especially for IgG aCL and aß2GPI and in thrombotic APS. IS-LRs per antibody and unit range were comparable across solid-phase platforms resulting in enhanced harmonization of result interpretation. Agreement between assays for identifying high levels was improved by semiquantitative interpretation compared with that by quantitative reporting. CONCLUSION: aCL and aß2GPI IgG/IgM moderate and high thresholds were determined for 4 analytical platforms. Thresholds improve harmonized interpretation of aCL/aß2GPI levels across platforms. The proposed thresholds should be verified in an independent case-control study to check interlaboratory transferability.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.