Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder

Obstetric antiphospholipid syndrome (APS) is now being recognized as a distinct entity from vascular APS. Pregnancy morbidity includes >3 consecutive and spontaneous early miscarriages before 10weeks of gestation; at least one unexplained fetal death after the 10th week of gestation of a morphologically normal fetus; a premature birth before the 34th week of gestation of a normal neonate due to eclampsia or severe pre-eclampsia or placental insufficiency. It is not well understood how antiphospholipid antibodies (aPLs), beyond their diagnostic and prognostic role, contribute to pregnancy manifestations. Indeed aPL-mediated thrombotic events cannot explain the obstetric manifestations and additional pathogenic mechanisms, such as a placental aPL mediated complement activation and a direct effect of aPLs on placental development, have been reported. Still debated is the possible association between aPLs and infertility and the effect of maternal autoantibodies on non-vascular manifestations in the babies. Combination of low dose aspirin and unfractionated or low molecular weight heparin is the effective treatment in most of the cases. However, pregnancy complications, in spite of this therapy, can occur in up to 20% of the patients. Novel alternative therapies able to abrogate the aPL pathogenic action either by interfering with aPL binding at the placental level or by inhibiting the aPL-mediated detrimental effect are under active investigation.