Non-Criteria Obstetric Antiphospholipid Syndrome: Myth or Reality?

Abstract

Women with adverse pregnancy outcomes suggestive of obstetric antiphospholipid syndrome (OAPS), but not fulfilling clinical and/or laboratory international classification criteria, are increasingly recognized both in clinical practice and in the 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 pre-eclampsia/eclampsia/signs of placental insufficiency, or recurrent implantation failure, as well as positive low-titers of antiphospholipid antibodies (aPLs) and non-classical aPLs. To address the NC-OAPS heterogeneity, a nomenclature proposal was developed. In recent 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 with antithrombotic, anticoagulant and/or immunomodulator agents, but several considerations must be made on the robustness and nuances of the scientific evidence. The objective of this review is to critically analyze the available evidence supporting the diagnosis of NC-OAPS, categorize its subsets, and evaluate the impact of treatment strategies on its outcome. We also remark on questions that are still unanswered, such as the lack of consensus on diagnostic criteria or treatment protocols.

Keywords: infertility; low-titer aPL; non-criteria obstetric antiphospholipid syndrome; recurrent implantation failure.

Figure 1

(A) Placental infarction (villous infarction) with intervillous space collapse and coagulative necrosis of chorionic villi in the left lower quadrant. Syncytial knot hyperplasia, visible as multiple dark hematoxylin-stained sprouts upon chorionic villi. H&E staining. Original magnification 2×. (B) Impaired spiral artery remodeling with persistence of the muscular wall (brown structures on the right side). Smooth-muscle actin immunohistochemistry counterstained with hematoxylin. Original magnification 4×. (C) Decidual inflammation. Chronic deciduitis is characterized by a dense lympho-plasmacytic inflammatory infiltrate dissecting decidual cells. H&E staining. Original magnification 40×. (D) The deposition of complement split product C4d signed with red arrows. Original magnification 40×.