Monocyte/Macrophage Infiltration in Thrombus and Outcomes of Stroke Patients with Monocyte/Macrophage-dominant Thrombus

Background Inflammatory cells may play a role in thrombus formation. However, the impact of monocytes in thrombosis and clinical characteristics of patients with monocyte-rich thrombus are less well understood. Methods A FeCl3-induced carotid thrombosis model in mice was used to study aged thrombus by ligating the distal carotid artery for 0.5, 1, 2, 3, 6, 24, 48, or 72 hours. In stroke patients, we used thrombi that were obtained during endovascular thrombectomy. Immunohistochemistry was performed to determine thrombus composition. We investigated monocyte/macrophage recruitment to arterial thrombus over time in mice, and compared clinical outcomes between stroke patients with the higher and the lower monocyte/macrophage compositions in thrombus. Results In 90 mice, CD68 (monocyte/macrophage) counts increased from 3 hours in a time-dependent manner, and decreased after 48 hours (p < 0.001). In 102 stroke patients, the higher monocyte/macrophage group had higher blood platelet counts (median 228 × 109/L, interquartile range [177–267] versus median 186 × 109/L, interquartile range [164–225], p = 0.036), less frequently parenchymal hematoma (8.0% versus 28.8%, p = 0.007), and more frequently functional independence (54.0% versus 32.7%, p = 0.030). In multivariable logistic regression analysis, the higher monocyte/macrophage group was independently associated with functional independence (odds ratio 4.954, 95% confidence interval 1.467–16.724, p = 0.010). Conclusion Monocytes/macrophages increasingly infiltrated the thrombus after a few hours in mouse arterial thrombosis model, suggesting their role in later stages rather than initial stages of thrombosis. Stroke patients with higher monocyte/macrophage counts had less frequent parenchymal hematoma and more frequent functional independence, suggesting that monocyte/macrophage-rich thrombi are a predictor of better clinical outcomes.