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–β₂-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%. Conclusion These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.

Objective: Catastrophic antiphospholipid syndrome (CAPS) is characterized by histopathologic evidence of small vessel thrombosis, dysfunction of multiple organs occurring over a short period of time, and laboratory confirmation of the presence of antiphospholipid antibodies (aPL). Treatment of CAPS focuses on anticoagulation therapy and on removal of aPL that promote thrombosis by activating endothelial cells, monocytes, and platelets. Studies in animal models support the hypothesis that a more targeted intervention, such as complement inhibition, may be an effective means to prevent aPL‐induced thrombosis. Herein we describe use of an inhibitor of complement activation to treat CAPS that was refractory to conventional therapy.Methods: Our patient was a young man who had recurrent CAPS characterized by multiple arterial thromboses in large and small vessels despite maximal anticoagulation, immunosuppression, and plasma exchange therapy. We treated him with eculizumab, an anti‐C5 monoclonal antibody that blocks activation of terminal complement.Results: Administration of eculizumab, at doses that blocked complement activity, aborted acute progressive thrombotic events, reversed thrombocytopenia, and was associated with no further clinical episodes of thrombosis during >3 years of therapy.Conclusion: This first report of the use and clinical efficacy of eculizumab, an inhibitor of complement activation, in the treatment of CAPS demonstrates both the importance of complement (specifically, terminal complement components) in the pathogenesis of CAPS and the therapeutic benefit of complement inactivation.

The catastrophic variant of the antiphospholipid syndrome (APS) is a life-threatening form of presentation of this syndrome that can be triggered by several factors. To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and puerperium. A review of the first 255 cases collected in the website-based "CAPS Registry" was undertaken. Three new and unpublished cases of catastrophic APS developed during pregnancy and puerperium were added. Fifteen cases were identified. The mean (range) age was 27 (17-38) years. Most patients had a previous unsuccessful obstetric history. In 7 of 14 (50%) cases with available medical history, the catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those patients with catastrophic APS triggered by other factors, except for a history of a higher prevalence of previous abortions (p<0.01). Several specific features were found, including the HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for the mothers (46%), and for the babies (54%). It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis.

Objective: To investigate whether an elevated interferon‐α (IFNα) level early in pregnancy is associated with poor pregnancy outcomes and to examine the relationship of an elevated IFNα level to angiogenic imbalance.Methods: Women were enrolled in a longitudinal case–control study of pregnant patients with lupus. Serum samples obtained monthly throughout pregnancy were assayed for IFNα and for the antiangiogenic factor soluble Flt‐1 and the proangiogenic factor placenta growth factor (PlGF). Each of 28 patients with systemic lupus erythematosus (SLE) with a poor pregnancy outcome was matched to an SLE patient with an uncomplicated pregnancy and to a pregnant healthy control. The effects of IFNα and/or soluble Flt‐1 on human endothelial cells and endothelial cell–trophoblast interactions were assessed.Results: Compared to SLE patients with uncomplicated pregnancies, patients with preeclampsia had increased IFNα levels before clinical symptoms. Patients without autoimmune disease who developed preeclampsia did not have increased IFNα levels. In SLE patients with low IFNα levels, marked angiogenic imbalance (higher soluble Flt‐1, lower PlGF, and higher soluble Flt‐1:PlGF ratios) preceded maternal manifestations of preeclampsia, whereas in SLE patients with high IFNα levels, preeclampsia occurred without evidence of systemic angiogenic imbalance. Treatment of human endothelial cells with soluble Flt‐1 induced expression of sFLT1 messenger RNA, and IFNα dramatically amplified responses to soluble Flt‐1. In a model of spiral artery transformation, only the combination of IFNα and soluble Flt‐1 disrupted the ability of trophoblast cells to remodel endothelial tube structures.Conclusion: Our findings identify a new mechanism by which IFNα induces an antiangiogenic milieu and increases the sensitivity of endothelial cells to soluble Flt‐1, and suggest that elevated IFNα levels may contribute to the pathogenesis of preeclampsia in some pregnant patients with SLE.