| First Author | Singh S | Year | 2019 |
| Journal | Blood | Volume | 134 |
| Issue | 12 | Pages | 970-978 |
| PubMed ID | 31395599 | Mgi Jnum | J:280273 |
| Mgi Id | MGI:6364457 | Doi | 10.1182/blood.2019000049 |
| Citation | Singh S, et al. (2019) Venous stasis-induced fibrinolysis prevents thrombosis in mice: role of alpha2-antiplasmin. Blood 134(12):970-978 |
| abstractText | Stasis of venous blood triggers deep vein thrombosis by activating coagulation, yet its effects on the fibrinolytic system are not fully understood. 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 alpha2-antiplasmin (alpha2AP), 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 alpha2AP(+/+) mice contained plasminogen activators, plasminogen activator inhibitor-1, plasminogen, and alpha2AP, which changed with thrombus age. Normal, alpha2AP(+/+) 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 alpha2AP(-/-) mice (P < .0001) or in alpha2AP(+/+) mice treated with an alpha2AP-inactivating antibody (P < .001). Venous stasis activated fibrinolysis, measured by D-dimer levels, in alpha2AP(-/-) mice vs alpha2AP(+/+) mice (P < .05). Inhibition of fibrinolysis by the indirect plasmin inhibitor epsilon-aminocaproic acid or by alpha2AP restored thrombosis in alpha2AP(-/-) mice. In addition to its effects on acute thrombosis, thrombus formation was also markedly suppressed in alpha2AP(-/-) mice vs alpha2AP(+/+) mice (P < .0001) 1, 7, and 14 days after ligation. We conclude that experimental venous stasis activates the fibrinolytic system to block the development of venous thrombosis. Suppression of fibrinolysis by alpha2AP appears essential for stasis-induced thrombus development, which suggests that targeting alpha2AP may prove useful for preventing venous thrombosis. |
