Catastrophic fetal-neonatal thrombosis: a thromboinflammatory concept and the role of antiphospholipid antibodies

OBJECTIVE: Fetal and neonatal thrombosis comprises a heterogeneous spectrum of disorders ranging from localized vascular events to rapidly progressive systemic thrombosis involving multiple vascular beds and organs. This review examines thromboinflammation and antiphospholipid antibodies (aPL) in severe fetal-neonatal thrombosis. METHODS: This narrative, hypothesis-generating review draws on a structured, non-systematic literature search through August 31, 2026, distinguishing direct fetal and neonatal evidence from adult and experimental findings. RESULTS: Neonatal hemostasis is characterized by a physiologically balanced but vulnerable state that may become destabilized by infection, hypoxia, endothelial injury, inflammation, and genetic or immune-mediated factors. Current evidence suggests that interactions between endothelial dysfunction, innate immune activation, platelets, coagulation, neutrophil extracellular traps, and the complement system may promote a transition from localized thrombosis to a self-amplifying thromboinflammatory process. However, a common mechanism of such progression has not been established across different fetal and neonatal thrombotic disorders. Maternal IgG aPL may cross the placenta, whereas aPL detected in some neonates may reflect presumed de novo production. The presence of aPL does not necessarily result in neonatal thrombosis, and additional prothrombotic factors reported in selected cases are consistent with, but do not establish, a "second-hit" or "multiple-hit" model. CONCLUSION: We propose catastrophic fetal-neonatal thrombosis as an unvalidated clinical and pathogenetic framework rather than a distinct disease entity. Paired maternal-neonatal testing and longitudinal antibody assessment may help clarify antibody origin, although delayed testing limits causal interpretation. Its potential value for earlier recognition and etiologically directed diagnostic evaluation requires prospective assessment.