Development of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-C Report: Assessment of Patient Scenarios (Derivation Cohort) and Refinement of Definitions.

Objective: The 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification criteria aim to identify patients with high likelihood of APS for research. Phases I/II of our four-phase methodological approach resulted in 27 candidate criteria organized in clinical and laboratory domains. Here, we summarize Phase III efforts to reduce and refine criteria using patient scenarios.

Thrombin generation test as a useful tool for improving disease severity stratification in antiphospholipid syndrome.

Background: Patients with antiphospholipid syndrome (APS) display a wide range of clinical manifestations with similar immunological profile with the presence of lupus anticoagulant in around 70% of them. Although antiphospholipid antibodies (aPL) profile influences the risk of thrombosis in APS, APS risk stratification remains to be improved.

Objectives: Our study aimed to evaluate thrombin generation test (TGT) interest to improve disease severity stratification in APS patients.

Vascular liver disorders in patients with antiphospholipid syndrome: a national retrospective multicentre study.

Objective: Antiphospholipid syndrome (APS) is an acquired autoimmune prothrombotic condition. Vascular liver disorders (VLD), such as portal vein thrombosis (PVT), Budd-Chiari syndrome (BCS) and porto-sinusoidal vascular disorder (PSVD), are rare and related to an underlying hypercoagulable state in most cases. We aimed to describe the clinical and immunological features of APS patients with VLD.

French protocol for the diagnosis and management of systemic lupus erythematosus.

Because Systemic Lupus Erythematosus (SLE) is a rare disease, and due to the significant prognostic impact of early management, a diagnosis confirmed by a physician with experience in SLE is recommended, for example from an expert center. Once the diagnosis is confirmed, existing manifestations should be identified in particular, renal involvement by an assessment of proteinuria, disease activity and severity should be determined, potential complications anticipated, associated diseases searched for, and the patient's socioprofessional and family context noted. Therapeutic management of SLE includes patient education on recognizing symptoms, understanding disease progression as well as when they should seek medical advice.

Thrombosis recurrence and major bleeding in non-anticoagulated thrombotic antiphospholipid syndrome patients: Prospective study from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) clinical database and repository ("Registry").

Background: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice.

Objectives: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups.

Patients/methods: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease.

Activities of Clinical Expertise and Research in a Rare Disease Referral Centre: A Place for Telemedicine beyond the COVID-19 Pandemic?

Introduction: Rare disease referral centres are entrusted with missions of clinical expertise and research, two activities that have to contend with numerous obstacles. Providing specialist opinions is time-consuming, uncompensated and limited by difficulties in exchanging medical data. Clinical research is constrained by the need for frequent research protocol visits.

2023 ACR/EULAR antiphospholipid syndrome classification criteria.

Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR.

Methods: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard.

Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β-glycoprotein I antibodies).

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.

Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2.

Relevance of inflammatory and complement activation biomarkers profiling in antiphospholipid syndrome patients outside acute thrombosis.

Objectives: To evaluate whether inflammatory and complement biomarkers are associated with specific characteristics of antiphospholipid syndrome (APS).

Methods: Serum levels of interleukin (IL)-1β (IL-1β), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, interferon-α (IFN)-α, IFN-γ, vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule (VCAM)-1, and plasma levels of soluble C5b-9 (sC5b-9), C3a, C4a, Bb fragment were measured in unselected APS patients. Twenty-five healthy blood donors were included as controls.

Precipitating factors of catastrophic antiphospholipid syndrome: the role of anticoagulant treatment in a series of 112 patients.

Background: The prevention of catastrophic antiphospholipid syndrome (CAPS), a rare complication of antiphospholipid syndrome (APS), is a major goal.

Objectives: We analyzed its precipitating factors, focusing on anticoagulation immediately before CAPS episodes.

Methods: We retrospectively analyzed patients in the French multicenter APS/systemic lupus erythematosus database with at least 1 CAPS episode.

Cutaneous Involvement in Catastrophic Antiphospholipid Syndrome in a Multicenter Cohort of 65 Patients.

Importance: Catastrophic antiphospholipid syndrome (CAPS) is a severe, rare complication of antiphospholipid syndrome (APS), but cutaneous involvement has not yet been adequately described.

Objective: To describe cutaneous involvement during CAPS, its clinical and pathological features, and outcomes.

Design, Setting, And Participants: This cohort study was a retrospective analysis of patients included in the French multicenter APS/systemic lupus erythematosus register (ClinicalTrials.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

Background: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome.

Methods: This multicentre, prospective, observational study was done at 76 centres in France.

Association between Routine Laboratory Parameters and the Severity and Progression of Systemic Sclerosis.

(1) Background: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease with a high mortality and morbidity rate. Identification of biomarkers that can predict the evolution of SSc is a key factor in the management of patients. The aim of this study was to assess the association of routine laboratory parameters, widely used in practice and easily available, with the severity and progression of SSc.

Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

Objective: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD).

Study Design: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected.

Dyslipidemia is insufficiently treated in antiphospholipid syndrome patients.

Objectives: Although dyslipidemia is a strong risk factor for thrombosis in antiphospholipid syndrome (APS), it has been poorly studied. This study aimed to assess lipids profile and risk factors for unachieved cholesterol levels in a real-life APS population.

Methods: Inclusion criteria were: APS diagnosis according to international classification criteria, referring to the out-patients clinic of our tertiary care center for their follow-up, and having a blood sample collection for lipids levels determination.

Molecular Spectrum in a French Cohort with Primary Dyslipidemia.

Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant hypercholesterolemia (ADH) or associated with elevated triglyceride levels in familial combined hyperlipidemia (FCHL). Rare variants are known in ADH and FCHL. We explored the molecular spectrum in a French ADH/FCHL cohort of 5743 unrelated probands.