A case of atypical infantile de novo antiphospholipid syndrome presenting with neonatal ischemic stroke without any triggering risk factors as a "second hit" and review of the literature.

Infantile antiphospholipid syndrome (APS) is a rare condition arising from either transplacental transfer of antiphospholipid antibodies (aPL) from the mother or de novo antibody production in the newborn. We present a unique case of cerebral artery thrombosis with persistently elevated anti-cardiolipin and anti-β2-glycoprotein-I antibodies, despite the absence of maternal aPL, suggesting primary de novo aPL synthesis. While the prevailing "second-hit" hypothesis suggests that additional thrombotic risk factors are required to trigger APS in infants, our case exhibited no prenatal, maternal, or thrombophilic risk factors. A literature review of 20 reported cases further confirmed that ours was the only case without additional thrombotic triggers among the 18 cases with complete data, challenging the necessity of a "second hit" in neonatal APS. Notably, aPL levels normalized over time without recurrence, raising questions about the need for long-term anticoagulation in select cases, including ours. These findings suggest a potential transient form of infantile APS and highlight the importance of sequential aPL testing to guide treatment. Further research is required to elucidate the mechanisms underlying de novo aPL synthesis and its clinical implications.