Venous stasis-induced fibrinolysis prevents thrombosis in mice: Role of A2-antiplasmin

Satish Singh, Aiilyan K. Houng, Guy L. Reed

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 a2-antiplasmin (a2AP), 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 a2AP1/1mice contained plasminogen activators, plasminogen activator inhibitor-1, plasminogen, and a2AP, which changed with thrombus age. Normal, a2AP1/1mice 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 a2AP2/2 mice (P < .0001) or in a2AP1/1mice treated with an a2AP-inactivating antibody (P < .001). Venous stasis activated fibrinolysis, measured by D-dimer levels, in a2AP2/2 mice vs a2AP1/1mice (P < .05). Inhibition of fibrinolysis by the indirect plasmin inhibitor «-aminocaproic acid or by a2AP restored thrombosis in a2AP2/2 mice. In addition to its effects on acute thrombosis, thrombus formation was also markedly suppressed in a2AP2/2 mice vs a2AP1/1mice (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 a2AP appears essential for stasis-induced thrombus development, which suggests that targeting a2AP may prove useful for preventing venous thrombosis.

Original languageEnglish (US)
Pages (from-to)970-978
Number of pages9
Issue number12
StatePublished - Sep 19 2019

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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