Abstract
Deep vein thrombosis (DVT) and its devastating complication, pulmonary embolism, are a severe health problem with high mortality. Mechanisms of thrombus formation in veins remain obscure. Lack of mobility (e.g., after surgery or long-haul flights) is one of the main factors leading to DVT. The pathophysiological consequence of the lack of mobility is blood flow stagnation in venous valves. Here, a model is described that mimics such flow disturbance as a thrombosis-driving factor. In this model, partial flow restriction (stenosis) in the inferior vena cava (IVC) is created. Closure of about 90% of the IVC lumen for 48 h results in development of thrombi structurally similar to those in humans. The similarities are: i) most of the thrombus volume is red, i.e., consists of red blood cells and fibrin, ii) presence of a white part (lines of Zahn), iii) non-denuded endothelial monolayer, iv) elevated plasma D-Dimer levels, and v) possibility to prevent thrombosis by low molecular weight heparin. Limitations include variable size of thrombi and the fact that a certain percentage of wild-type mice (0 - 35%) may not produce a thrombus. In addition to visual observation and measurement, thrombi may be visualized by non-invasive technologies, such as ultrasonography, which allows for monitoring the dynamics of thrombus development. At shorter time points (1 - 6 h), intravital microscopy may be applied to directly observe events (e.g., recruitment of cells to the vessel wall) preceding thrombus formation. Use of this method by several teams around the world has made it possible to uncover basic mechanisms of DVT initiation and identify potential targets that might be beneficial for its prevention.
Highlights
Deep vein thrombosis (DVT) is the development of thrombi in deep veins, usually in legs
Blood flow in veins depends on the muscle pump and limb immobilization results in stagnant blood flow in venous valves, which leads to thrombosis
Partial flow restriction in the inferior vena cava (IVC) mimics conditions created in human venous valves and results in the formation of a thrombus similar in structure to human thrombi[6]
Summary
Deep vein thrombosis (DVT) is the development of thrombi in deep veins, usually (but ) in legs. In which residual flow is maintained in the vessel, application of stasis completely stops the flow and limits the accessibility of systemically administered substances to the thrombosis site It seems that mechanisms underlying thrombosis induced by stenosis and stasis are different: stenosis results in the development of local inflammation (activation of the endothelium, release of Weibel-Palade body content, recruitment of immune cells and platelets to the vessel wall) causing "immunothrombosis"[6,9,17], whereas stasis seems to induce rather thrombosis based, in particular, on tissue factor and other coagulation and fibrinolysis-related mechanisms[18,19,20]. Mice on C57BL/6 background, 8 - 12 week old, 19 - 25 g body weight, of both genders are used
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