Non-Criteria Obstetric Antiphospholipid Syndrome: Myth or Reality?

Women with adverse pregnancy outcomes suggestive of obstetric antiphospholipid syndrome (OAPS) but not fulfilling the clinical and/or laboratory international classification criteria are increasingly recognized both in clinical practice and in literature. This entity is termed non-criteria OAPS (NC-OAPS). It includes clinical scenarios such as two unexplained pregnancy losses, three non-consecutive pregnancy losses, late preeclampsia/eclampsia/signs of placental insufficiency, or recurrent implantation failure, as well as positive low-titers of antiphospholipid antibodies (aPL) and non-classical aPL. Given the heterogeneity of NC-OAPS, an attempt to organize it in subsets was accomplished in the form of a nomenclature proposal. In the last years, retrospective and prospective cohort studies have been designed to clarify the characteristics and outcomes of the different subsets of NC-OAPS. In general, the studies support that NC-OAPS may benefit from treatment, but several considerations must be made on the robustness and nuances of the scientific evidence. In this review we examine the available evidence supporting the diagnosis of NC-OAPS, the features of its different subsets, and the impact of treatment strategies on its outcome, pointing out the questions that are still unanswered.