Table 2.

Phase II Survey A Results and Subsequent Steering Committee and Domain Subcommittee Decisions/Rationale for Item Reduction During New Antiphospholipid Syndrome Classification Criteria Development

Candidate Criteria and Domains	Committee Consensus Supported by the Literature Review for Items Eliminated (Despite Score >2) or Retained (Despite Score <2)
I: Cardiopulmonary • Retained1: Cardiac Valve (CV) Vegetation, CV Thickening, Alveolar Hemorrhage (AH)*  -------------------------------------------------------------------------------------------------- • Eliminated2: Pulmonary HTN (thromboembolic [TE])*, Heart Failure Due to Ischemia	AH: Considered distinct entity associated with aPL(37);retained for Phase 3 ‘microvascular’ domain. ----------------------------------------------------------------------------- Pulm HTN (TE): Commonly due to pulmonary embolism in APS which is redundant with the item VTE (chronic TE pulmonary hypertension[Group 4])(38, 39).
II: Dermatologic • Retained1: Livedo Racemosa (LRa), Livedoid Vasculopathy  -------------------------------------------------------------------------------------------------- • Eliminated2: Livedo Reticularis (LRe)*, Atrophie Blanche de Milan, Pyoderma Gangrenosum-like Skin Ulcers, Anetoderma	---------------------------------------------------------------------------- LRe: Relatively common in general population; not as specific as LRa for APS classification(40, 41).
III: Hematologic: • Retained1: Thrombocytopenia (mild), Thrombocytopenia (severe)*  -------------------------------------------------------------------------------------------------- • Eliminated2: Microangiopathic Hemolytic Anemia, Coombs+ without Hemolytic Anemia	Thrombocytopenia (severe): Given that other more likely explanations than aPL exist, committee proposed evaluating “cut-off” thresholds (mild-moderate-severe) in Phase 3 to improve specificity(42, 43). ----------------------------------------------------------------------------
IV: Neurology: • Retained1: Transient Ischemic Attack (TIA) without additional risk factor (ARF) (age <55), Transient Ischemic Attack (TIA) without additional risk factor (ARF) (age >55)*, Transient Ischemic Attack (TIA) with additional risk factor (ARF) (age <55)*, Transient Ischemic Attack (TIA) with additional risk factor (ARF) (age >55)*, Acute Ischemic Encephalopathy (age<55y)  -------------------------------------------------------------------------------------------------- • Eliminated2: Seizure/Epilepsy*, Atypical Multiple Sclerosis-like Disease, Migraine Responsive to Anticoagulation, Chorea, Cerebral White Matter Lesions, Cognitive Dysfunction, Longitudinal Extensive Transverse Myelitis, Multi-Infarct Dementia (<65y)	TIA: Retained for Phase 3 independent of age and ARF, with plan to further analyze in context of age and ARF during case collection. ----------------------------------------------------------------------------- Seizure/Epilepsy: Rarely associated with aPL; mainly secondary to stroke in aPL positive patients; poor definability(5, 44).
V: Obstetric: • Retained1: Fetal Loss (Single*/Recurrent/Consecutive), Stillbirth, Early Pregnancy Loss (Recurrent*), Pre-eclampsia (early/severe/mild/late*), HELLP Syndrome*, Eclampsia, Intrauterine Growth Restriction*  --------------------------------------------------------------------------------------------------- • Eliminated2: Chorea Gravidarum, Pregnancy-induced Hypertension	Obstetric Morbidity: Re-structured domain for evaluation of individual items during Phase 3 case collection. (45, 46). -----------------------------------------------------------------------------
VI: Vascular • Retained1: Arterial Thrombosis (AT) without ARF (age <55), AT with ARF (age< 55)*, AT without ARF (age >55)*, AT with ARF (age >55)*, Venous Thromboembolism (VTE) without ARF (age <55y), VTE with ARF (age < 55y)*, VTE without ARF (Age > 55)*, VTE with ARF (age>55)*, Superficial Venous Thrombosis (SVT) without ARF (age <55y), SVT with ARF (age < 55y)*, SVT without ARF (age > 55)*, SVT with ARF (age>55)*	AT/VTE/SVT: SVT considered to have lower specificity for aPL than AT or VTE(5, 47). However, all three retained for Phase 3 independent of age and risk factors; committee agreed to include age thresholds and additional thrombosis risk factors during case collection.
VII: Renal/Abdominal: • Retained1: Nephrotic Syndrome, Adrenal hemorrhage
VIII: Pathology: • Retained1: Thrombosis/infarction without Vasculitis, Pulmonary Capillaritis (PC)*, Fibrous Interstitial Hyperplasia (FIH)*, Focal Cortical Atrophy (FCA)	PC/FIH: PC increasingly associated with aPL(37). FIH considered the most frequent chronic lesion in primary aPL nephropathy(48). Retained and restructured both items for Phase 3 data collection under ‘microvascular’ domain.
IX. Laboratory Part I • Retained: Lupus Anticoagulant Test
X. Laboratory Part II • Retained1: Anticardiolipin Antibodies (aCL) IgG/IgM*, Anti-β2Glycoprotein-I Antibodies (aβ2GPI) IgG/IgM*  ------------------------------------------------------------------------------------------------- • Eliminated2: Anti-Domain-I Antibodies (aDI)*, Anti-Phosphatidylserine-Prothrombin Antibodies (aPS/PT)*, aCL IgA, aβ2GPI IgA, Anti-Prothrombin antibodies	aCL & aβ2GPI IgM: Wide variation in survey scores for aPL ELISA IgM based on titer level and single/persistent positivity. aPL ELISA IgM noted to have lower specificity than IgG for APS. Final decision was to collect detailed aPL ELISA isotype and titer information during phase 3 (49, 50). ---------------------------------------------------------------------------- aDI & aPS/PT: limited commercial availability; additional research needed to define feasibility, clinical correlation, and standardization(4).

¹“Reason for retention” was based on committee agreement, supported by survey Likert score ≥2. Any item scoring <2 but retained based on committee discussions is marked with an asterisk (*), and the reason is explained in the notes section.

²“Reason for elimination” was based on committee agreement, supported by survey Likert score <2 (low specificity). Any item scoring ≥2 but eliminated based on committee discussions is marked with an asterisk (*) explained in the notes section