Postviral Anti-PF4 Immunothrombosis in Children: A Narrative Review with Practical Guidance

Postviral antiplatelet factor 4 (PF4) immunothrombosis is an emerging pediatric entity characterized by thrombocytopenia, thrombosis, and markedly elevated D-dimer levels and anti-PF4 antibodies. It shares immunopathologic features with vaccine-induced immune thrombotic thrombocytopenia but arises after natural infection, most often adenoviral infection. We reviewed pediatric cases and mechanistic studies identified through PubMed and reference screening (latest search: November 20, 2025), with a focus on pathophysiology, differential diagnosis, laboratory evaluation, and treatment. We identified 10 pediatric patients, with a reported mortality rate of 20%. Children typically presented with acute severe headache, focal neurological deficits, and thrombocytopenia 5-14 days after recent viral illness. All reported cases had markedly increased D-dimers. Rapid immunoassays for heparin-induced thrombocytopenia were often negative; PF4-specific enzyme-linked immunosorbent assay and PF4-enhanced functional assays were positive. Treatments in published cases included anticoagulation (9/10 cases), intravenous immunoglobulin (5/10 cases), and plasma exchange therapy (3/10 cases). On the basis of these findings and mechanistic parallels, we propose a diagnostic and therapeutic approach, acknowledging the limited evidence base. In conclusion, postviral anti-PF4 immunothrombosis in children, although rare, is potentially fatal and likely underrecognized. Further research is needed to establish standardized diagnostic criteria and evidence-based treatment protocols.