Introduction: While COVID-19 vaccines substantially reduced global mortality, rare hypercoagulable safety signals such as immunothrombosis emerged. In critically ill ICU patients, pre-existing systemic inflammation and endothelial strain may compound these thrombotic risks within the delicate pulmonary vasculature. Consequently, this study aimed to evaluate the incidence and clinical characteristics of pulmonary vascular thrombosis in ICU patients following COVID-19 vaccination.

Material and methods: This cross-sectional study was conducted at Imam Reza Center, Tabriz, recruiting 250 ICU patients selected via convenience sampling based on Cochran’s formula. Eligible post-vaccination patients were evaluated for pulmonary vascular thrombosis using CTPA. Demographic, clinical, hemodynamic, and laboratory data—including D-dimer and anti-PF4 levels—were abstracted from medical records and analyzed to identify clinical predictors.

Results: Pulmonary vascular thrombosis significantly correlated with thrombocytopenia (61.8% vs. 17.6%, P < 0.001), elevated D-dimer (6.84±3.42 vs. 2.22±1.28 mg/L FEU, P<0.001), and higher mPAP (31.40±8.24 vs. 22.33±4.98 mmHg, P<0.001). Multivariable regression identified anti-PF4 positivity (aOR:6.842, 95% CI:2.418–19.362, P<0.001), thrombocytopenia (aOR:3.428, 95% CI:1.584–7.418, P=0.002), and adenoviral vaccination (aOR:2.815, 95% CI:1.382–5.735, P=0.004) as independent predictors.

Conclusion: Post-vaccination pulmonary vascular thrombosis in critically ill patients is independently driven by adenoviral vector platforms, thrombocytopenia, and anti-PF4 seropositivity, leading to marked hemodynamic compromise. Routine screening with D-dimer, platelet counts, and anti-PF4 antibody assays facilitates early risk stratification, timely intervention, and mitigated ICU mortality.