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

Abstract

Background Inflammatory cells may play a role in thrombus formation. However, the impact of monocytes in thrombosis and clinical characteristics of patients withmonocyte-rich thrombus are less well understood. MethodsAFeCl3-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. Instroke patients, we used thrombi that wereobtained during endovascular thrombec-tomy. Immunohistochemistry was performed to determinethrombus composition. Weinvestigated monocyte/macrophage recruitment to arterial thrombus over time inmice, and compared clinical outcomes between stroke patients with the higher and thelower monocyte/macrophage compositions in thrombus. ResultsIn 90 mice, CD68 (monocyte/macrophage) counts increased from 3hours ina time-dependent manner, and decreased after 48 hours (p<0.001). In 102 strokepatients, the higher monocyte/macrophage group had higher blood platelet counts(median 228 x 10(9)/L, interquartile range [177-267] versus median 186 x 10(9)/L,interquartile range [164-225],p = 0.036), less frequently parenchymal hematoma(8.0% versus 28.8%,p<1/4>0.007), and more frequently functional independence (54.0%versus 32.7%,p 1/40.030). In multivariable logistic regression analysis, the highermonocyte/macrophage group was independently associated with functional indepen-dence (odds ratio 4.954, 95% confidence interval 1.467-16.724,p = 0.010). ConclusionMonocytes/macrophages increasingly infiltrated the thrombus after afew hours in mouse arterial thrombosis model, suggesting their role in later stages ratherthan initial stages of thrombosis. Stroke patients with higher monocyte/macrophagecounts had less frequent parenchymal hematoma and more frequent functional indepen-dence, suggesting that monocyte/macrophage-rich thrombi are a predictor of betterclinical outcomes