Pentasystem embolism associated with transient antiphospholipid antibodies in severe M. pneumoniae pneumonia: a “Dual-Hit” case report and systematic review

Background Thromboembolism is a critical complication of severe Mycoplasma pneumoniae pneumonia (SMPP) in children, yet its clinical spectrum and immunothrombotic mechanisms remain poorly defined. The “dual-hit” hypothesis—synergy between infection-induced inflammation and transient antiphospholipid antibodies (aPLs)—lacks integrated clinical validation. Methods We report a case of extensive multi-system thrombosis in a 6-year-old boy with SMPP. A systematic review of literature (January 2020–December 2025) identified 19 studies comprising 199 pediatric cases. Results In the index case, thrombosis coincided with hyperinflammation and transient aPLs, which seroconverted to negative upon recovery. Pooled analysis showed multi-system involvement in 27.1% of cases (54/199). Among tested patients (n = 65; 32.7% of the cohort), aPL positivity was 69.2% (45/65). Most patients achieved favorable outcomes with anticoagulation and immunomodulation. Conclusion This study is consistent with the “dual-hit” model in SMPP, where systemic inflammation may prime the endothelium and transient aPL positivity coincides with an extensive thrombotic burden. The high prevalence of multi-system involvement supports low-threshold vascular imaging and aPLs screening, along with biomarker-guided management. Transient aPLs should be interpreted as a potential risk-amplifying biomarker rather than a proven causal driver of thrombosis.