EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies

Objectives. aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria ('criteria aPL') and at titres lower than thresholds considered by classification criteria ('low-titre aPL') on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (P-PM). Methods. Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. Results. EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact P-PM when at low titres and when fulfilling classification criteria. P-PM was further stratified upon the aPL tests: aCL IgG/IgM and anti-beta 2-glycoprotein I (beta 2GPI) IgM, alone or combined, do not affect the basal risks of P-PM, an increase occurs in case of positive LA or anti-beta 2GPI IgG. LDASA significantly affects P-PM exclusively in women with low-titre aPL without anti-beta 2GPI IgG. The LDASA+LMWH combination significantly reduces P-PM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-beta 2GPI IgG. In this group, the addition of HCQ further reduces P-PM, although not significantly. Conclusion. EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPLpositive pregnant women.

Automated summary

This study investigates the impact of aPL positivity at different titres on pregnancy morbidity, finding that low-titre aPL and aPL fulfilling classification criteria significantly impact the risk of PM. The combination of LDASA and LMWH can significantly reduce the probability of PM in all women with low-titre aPL and criteria aPL.