The effects of blood flow on the structure of venous thrombi

Objectives Thrombolytic therapy can eliminate thrombotic masses from the deep veins, but its effectiveness is not always predictable. We hypothesize that blood flow may influence the composition of an acute venous thrombus contributing to unpredictable outcomes. The aim of the study was to take advantage of two available well-established models to compare venous thrombus composition under flow and stasis conditions in vivo. Methods C57BL/6 mice, 10-12 weeks old, weighing 20-25g, were used in electrolytic (EIM) and ligation (LM) models of VT. Four groups (n = 5) were used to compare the structure of acute (Day (2) and subacute (Day (6) thrombus in the EIM and LM. Venous thrombus was harvested for thrombus weight (TW) measurement and histology. Expression of PAI-1, t-PA, u-PA, and alfa-2-antiplasmin in the vein wall and D-dimer levels in plasma were investigated at Day 2 and 6. Results Acute venous thrombus within the EIM was significantly smaller compared to LM (6.2 ± 3.6 vs 26.2 ± 3.6, P < .05 ). Thrombus formed within the EIM had a significantly higher amount of plasminogen, especially on the surface and in the tail of the thrombus. In addition, a significantly higher concentration of circulating D-Dimer was found within the EIM. Conclusions Regional venous blood flow pattern may significantly affect the structure and composition of the venous thrombotic masses. Non-occlusive thrombus has a higher potential to be targeted by the fibrinolytic system and fibrinolytic therapy due to a higher plasminogen content and accessibility for plasminogen activators.