OBJECTIVE: To define the spatial-morphologic characteristics of venous thrombus formation, propagation, and resolution at the submicron level over time.
METHODS: Using a murine model of stasis-induced deep vein thrombosis along with scanning electron microscopy and immunohistology, we determine the specific structural, compositional, and morphologic characteristics of venous thrombi formed after 4 days and identify the changes that take place during resolution by day 7. Comparison is made with the structure and composition of venous thrombi formed in mice genetically deficient in plasminogen activator inhibitor type 1.
RESULTS: As venous thrombus resolution progresses, fibrin exists in different structural forms, and there are dynamic cellular changes in the compositions of leukocytes, platelet aggregates, and red blood cells. Intrathrombus microvesicles are present that are not evident by histology, and red blood cells in the form of polyhedrocytes are an indicator of clot contraction. Structural evidence of fibrinolysis is observed early during thrombogenesis and is accelerated by plasminogen activator inhibitor type 1 deficiency.
CONCLUSIONS: The results reveal unique, detailed ultrastructural and compositional insights along with documentation of the dynamic changes that occur during accelerated resolution that are not evident by standard pathologic procedures and can be applied to inform diagnosis and effectiveness of thrombolytic treatments to improve patient outcomes.
目的:定义静脉血栓形成的空间形态特征,传播,随着时间的推移,亚微米级别的分辨率。
方法:使用小鼠血瘀诱导的DVT模型以及扫描电子显微镜和免疫组织学,我们确定了具体的结构,4天后形成的静脉血栓的组成和形态特征,并确定在第7天解决期间发生的变化。比较了在遗传上缺乏纤溶酶原激活剂抑制剂1型(PAI-1)的小鼠中形成的静脉血栓的结构和组成。
结果:随着静脉血栓消退的进展,纤维蛋白以不同的结构形式存在,并且在白细胞的组成中存在动态的细胞变化,血小板聚集体和红细胞。血栓内微泡存在,组织学不明显,和红细胞形式的多角体细胞是凝块收缩的指标。早期观察到纤维蛋白溶解的结构证据,在血栓形成过程中,并因PAI-1缺乏而加速。
结论:结果显示,详细的超微结构和成分的见解,以及在加速分辨率过程中发生的动态变化的文件,这些变化在标准病理程序中并不明显,并可用于告知溶栓治疗的诊断和有效性,以改善患者的预后。