Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1.
Circ Res
; 99(11): 1261-9, 2006 Nov 24.
Article
in En
| MEDLINE
| ID: mdl-17068293
ABSTRACT
Influenza infections increase the risk of diseases associated with a prothrombotic state, such as venous thrombosis and atherothrombotic diseases. However, it is unclear whether influenza leads to a prothrombotic state in vivo. To determine whether influenza activates coagulation, we measured coagulation and fibrinolysis in influenza-infected C57BL/6 mice. We found that influenza increased thrombin generation, fibrin deposition, and fibrinolysis. In addition, we used various anti- and prothrombotic models to study pathways involved in the influenza-induced prothrombotic state. A reduced capacity to generate activated protein C in TM(pro/pro) mice increased thrombin generation and fibrinolysis, whereas treatment with heparin decreased thrombin generation in influenza-infected C57Bl/6 mice. Thrombin generation was not changed in hyperfibrinolytic mice, deficient in plasminogen activator inhibitor type-1 (PAI-1(-/-)); however, increased fibrin degradation was seen. Treatment with tranexamic acid reduced fibrinolysis, but thrombin generation was unchanged. We conclude that influenza infection generates thrombin, increased by reduced levels of protein C and decreased by heparin. The fibrinolytic system appears not to be important for thrombin generation. These findings suggest that influenza leads to a prothrombotic state by coagulation activation. Heparin treatment reduces the influenza induced prothrombotic state.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Orthomyxoviridae
/
Blood Coagulation
/
Protein C
/
Plasminogen Activator Inhibitor 1
/
Orthomyxoviridae Infections
/
Fibrinolysis
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Circ Res
Year:
2006
Type:
Article
Affiliation country:
Netherlands