Background:An international multi-disciplinary effort is underway to develop rigorous, new, consensus- and evidence-based classification criteria for Antiphospholipid Syndrome (APS). The methodological approach includes four phases; we have previously presented phases I and II (item generation and reduction), which resulted in 27 candidate criteria1organized in laboratory and clinical domains.Objectives:Phase III (item weighting/threshold identification) is currently underway; here we report initial Phase III case collection results.Methods:We used REDCap, a secure data system, for Phase III international case collection. The candidate criteria of 27 items at the end of Phase II was represented in a standardized case collection form. We asked international physicians interested in APS to provide and rate cases using a Likert scale (+3 to -3: highly likely to highly unlikely to be APS). Cases with higher scores (+2 or +3) were categorized as “highly likely” APS, whereas lower scores (+1 to -3) were categorized as “equivocal or unlikely” APS.Results:We collected 314 potential APS cases (mean age 43.8±14.4 years; 79% female; and 77% white) between 6/2019-8/2019 from 17 sites in Europe (47%), North America (41%), and South America (11%). Majority of cases were potential primary APS (64%); 137 were rated as “highly likely” and 177 as “equivocal or unlikely” APS. Lupus anticoagulant, antiβ2glycoprotein-I antibody IgG/M, anticardiolipin antibody IgG, arterial thrombosis, venous thromboembolism, microvascular disease, fetal loss between 16-34 weeks, severe preeclampsia, severe placental insufficiency, cardiac valve disease, and low platelet count occurred with higher frequency in the APS cases categorized as “highly likely” (Table).Conclusion:International collection of cases spanning the spectrum of “highly likely” to “equivocal or unlikely” APS provide “real world” assessment of patients being referred for APS evaluation. In next steps, proposed candidate criteria will be further refined, organized, and weighted, and a preliminary threshold for APS classification will be determined.References:[1]Barbhaiya M et al. Phase II Results [abstract]. Arthritis Rheumatol. 2019;71 (suppl 10).Table.Characteristics of Potential APS Cases Categorized by Physician AssessmentCandidate Relative Criteria, n (%)Total(n=314)Highly Likely APS(n=137)Equivocal or Unlikely APS(n=177)LABORATORYLupus Anticoagulant Test208 (66)117 (85)91 (51)Anticardiolipin Antibody• IgG170 (54)90 (66)80 (45)• IgM138 (44)61 (45)77 (44)Antiβ2glycoprotein-I Antibody• IgG99 (32)66 (48)33 (19)• IgM79 (25)47 (34)32 (18)CLINICALMacrovascular• Superficial Vein Thrombosis15 (5)4 (3)11 (6)• Venous Thromboembolism95 (30)63 (46)32 (18)• Transient Ischemic Attack27 (9)13 (10)14 (8)• Arterial Thrombosis82 (26)58 (42)24 (14)Microvascular*86 (27)62 (45)24 (14)Obstetric**• Embryonic Loss (<10 weeks [w])85 (45)34 (42)51 (48)• Fetal Loss (10w–<16w)20 (11)9 (11)11 (10)• Fetal Loss (16w–34w)42 (22)32 (40)19 (18)• Severe Preeclampsia (<34w)27 (14)18 (22)9 (8)• Severe Placental Insufficiency (<34w)22 (12)13 (16)9 (8)Cardiac Valve Disease***32 (10)21 (15)11 (6)Thrombocytopenia <150 G/L72 (23)43 (31)29 (16)*Livedo racemosa, livedoid vasculopathy, adrenal hemorrhage, acute ischemic enceophalopathy, cardiac microvascular disease, pulmonary hemorrhage, acute and/or chronic antiphospholipid-related nephropathy; **Total number of patients ever pregnant: 188 (highly likely APS: 81; unlikely APS: 107) ***Valve thickening and/or vegetation.Acknowledgments:The project is supported by ACR/EULARDisclosure of Interests:Medha Barbhaiya: None declared, Doruk Erkan: None declared, Yasaman Ahmadzadeh: None declared, Karen Costenbader Grant/research support from: Merck, GSK, Consultant of: Merck, GSK, Lily, Astra Zeneca, Janssen, Raymond Naden: None declared, Stéphane Zuily: None declared

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.

Background and Purpose: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale. Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2–infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries’ health expenditure on outcomes. Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were <55 years of age, and 105 (24.4%) patients had no identifiable vascular risk factors. Among acute ischemic stroke patients, 44.5% (126 of 283 patients) had large vessel occlusion; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median National Institutes of Health Stroke Scale (8 [3–17] versus 11 [5–17]; P =0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; P <0.001) in countries with middle-to-high health expenditure when compared with countries with lower health expenditure. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144 (37.8%) were asymptomatic at the time of admission for SARS-CoV-2 infection. Conclusions: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.

Objectives Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody (aPL)-positive patients with or without a history of thrombosis in an international cohort. Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. Methods In this cross-sectional study, we analyzed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analyzed the demographic, clinical, and laboratory characteristics based on two subgroups: (1) thrombotic APS patients with high versus low damage; and (2) non-thrombotic aPL-positive patients with versus without damage. Results Of the 826 aPL-positive patients included in the registry as of April 2020, 576 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 164 non-thrombotic). In the thrombotic group, hyperlipidemia (OR 1.82, 95%CI 1.05–3.15, adjusted p= 0.032), obesity (OR 2.14, 95%CI 1.23–3.71, adjusted p= 0.007), aβ2GPI high titers (OR 2.33, 95%CI 1.36–4.02, adjusted p= 0.002), and corticosteroids use (ever) (OR 3.73, 95%IC 1.80–7.75, adjusted p&lt; 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55, 95%CI 1.82–11.35, adjusted p= 0.001) and hyperlipidemia (OR 4.32, 95%CI 1.37–13.65, adjusted p= 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95%CI 0.075–0,77, adjusted p= 0.016). Conclusions DIAPS indicates substantial damage in aPL-positive patients in APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.