American college of rheumatologist eular apls 2023.pptx

classification of APLS latest EULAR APLS 2023

1. CME hemostatis Zahabiya P109291

2. Outline Introduction- APLS Definition Evolution of APLS classification criteria Latest APLS classification 2023 ACR/EULAR The laboratory testing updates in APLS according to the 2023 ACR/EULAR Summary- Sydney 2006 vs ACR/EULAR 2023 classification Strengths and limitations C onclusion

3. Introduction Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistent antiphospholipid antibodies ( aPL ).

4. Evolution of APLS classification criteria

5. 1999 Sapporo classification

6. Revised Sapporo 2006/Sydney

7. Sapporo 1999 vs Revised Sapporo 2006 (Sydney)- Laboratory

8. ACR/EULAR APS 2023 There has been advancements in understanding of APS include better characterisation of non-thrombotic clinical manifestations, identification of the role of traditional thrombosis risk factors in aPL -positive individual and risk stratification by aPL profile. In revised Sapporo criteria, broad clinical definitions caused inclusion of ‘heterogenous’ group of ‘ aPL positive” patients with different risk profiles for research.

9. 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.

10. Methods Four phases Phase I, criteria generation by surveys and literature review Phase II, criteria reduction by modified Delphi and nominal group technique exercises. 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 Phase IV, validation using independent adjudicators’ consensus as the gold standard.

11. 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. 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%.

12. Clinical criteria

13. Laboratory criteria

14. Novel laboratory features Quantifying single-, double-,and triple- aPL positivity based on different domains and weights; Separating aCL /anti-β2GPI IgG and IgM isotypes, to avoid including aPL - positive patients with isolated aCL /anti-β2GPI IgM isotypes ( ie , no other aPL positivity) in the same research studies as those with aCL /anti-β2GPI I IgG isotypes; Defining 2 levels of aCL /anti-β2GPI positivity that wil be interpreted as clinically relevant by most investigators.

15. Summary of 2023 ACR/EULAR vs Sydney 2006

16. Criteria 2023 ACR/EULAR Classification Clinical Weighted assessment Well-defined microvascular domains Restructured definition of pregnancy morbidity and addition of cardiac valve disease and thrombocytopenia Laboratory Quantifying single-, double-,and triple- aPL positivity based on different domains and weights Separating IgM and IgG isotypes for aCL and anti-B2GP1 antibodies Determining 2 levels of aCL and anti-B2GP1 IgG (moderate and high) aCL ) and anti– β2- glycoprotein I antibody (anti- β2 GPI) thresholds of moderate and high should be determined based on standardised ELISA results , not based on other testing modalities such as new automated platforms with variations of the solid phase ( eg , magnetic microparticles and microspheres) and various detection systems ( eg , chemiluminescent immunoassay (CLIA), multiplex flow immunoassay (MFI), or flow cytometry). Interval between aPL ab positivity and clinical sx Less than 3 years , compared to less than 5 years in Sydney criteria Sensitivity and specificity Sensitivity- 84% (Sydney- 99%) Specificity- 99% (Sydney- 86%)

17. Strengths Inclusion of international cases capturing spectrum of APS, reducing risk of selection bias and increasing generalizability (Asians: 3-6 %) Multidisciplinary participants in phase III and IV were different  avoid bias of circular reasoning. Two independent validation cohort with similar performance  strengthens results New classification allows for individual domain modification allowing for future incorporation of additional clinical or new commercially available laboratory items if shown to be highly specific for APS, or new VTE and CVD risk factors based on future guidelines. “Entry criteria” to reflect current thinking that only cases with at least a minimal degree of clinical and laboratory suspicion for APS should be considered for classification  increase specificity Absolute point requirements from both clinical and laboratory domains refines previous single threshold models and more accurately reflects actual APS clinical decision- making.

18. Limitations Do not represent all possible subpopulations – for eg ; in the clinical scenario of an acceptable aPL profile and concomitant heparin- induced thrombocytopenia, the hematologic domain should not be scored. Similarly, in a patient with systemic lupus erythematosus (SLE) with an acceptable aPL profile and preeclampsia, the obstetric item should not be scored if the preeclampsia can be equally or more likely explained as attributable to SLE  decrease sensitivity Independent adjudicators may still have inherent bias towards established criteria

19. Conclusion Using rigorous data- driven and expert- based methodology, including international multidisciplinary collaborators with APS expertise, methodologists, and patients, we have incorporated heterogenous aPL - related clinical and laboratory manifestations into a set of hierarchically clustered, weighted, and risk- stratified classification criteria reflecting current thinking about APS, providing high specificity and an improved foundation for APS research. **While the laboratory criteria are more straight-forward and less complex, application of the clinical criteria maybe challenging.

20. Thank you..