Venous stasis-induced fibrinolysis prevents thrombosis in mice: role of {alpha}2-antiplasmin

We examined the relationship between stasis, fibrinolysis, and the development of experimental venous thrombosis. Effects of stasis-induced deep vein thrombosis and fibrinolysis on thrombosis were examined by inferior vena cava ligation in congenic mice with and without α2-antiplasmin (α2AP), the primary inhibitor of plasmin. Venous thrombus weights were measured and thrombus composition was determined by Martius scarlet blue and immunofluorescence staining. Venous thrombi from α2AP+/+ mice contained plasminogen activators, plasminogen activator inhibitor-1, plasminogen, and α2AP, which changed with thrombus age. Normal, α2AP+/+ mice developed large, occlusive thrombi within 5 hours after ligation; thrombi were even larger in plasminogen-deficient mice (P < .001). No significant thrombus formation was seen in α2AP–/– mice (P < .0001) or in α2AP+/+ mice treated with an α2AP-inactivating antibody (P < .001). Venous stasis activated fibrinolysis, measured by D-dimer levels, in α2AP–/– mice vs α2AP+/+ mice (P < .05). Inhibition of fibrinolysis by the indirect plasmin inhibitor -aminocaproic acid or by α2AP restored thrombosis in α2AP–/– mice. In addition to its effects on acute thrombosis, thrombus formation was also markedly suppressed in α2AP–/– mice vs α2AP+/+ mice (P < .0001) 1, 7, and 14 days after ligation. We conclude that exper...

Source: Blood - September 18, 2019 Category: Hematology Authors: Singh, S., Houng, A. K., Reed, G. L. Tags: Thrombosis and Hemostasis Source Type: research