Inhibition of fibrinolytic activity in-vivo by dexamethasone is counterbalanced by an inhibition of platelet aggregation.
Dexamethasone decreases the fibrinolytic activity in cultured medium of several cell types by an induction of PAI-1 synthesis. As a result of this enhanced PAI-1 synthesis a prothrombotic state is expected in patients treated with dexamethasone. However, such a prothrombotic state is not reported as a major adverse effect. We have studied the effects of dexamethasone (dose range: 0.1-3.0 mg/kg) on the fibrinolytic system of rats after a 5 day pretreatment period. It appeared that dexamethasone dose dependently decreased the fibrinolytic activity (a dose of 1 mg/kg showed a reduction of about 40%). This reduced fibrinolytic activity could be functionally translated into an increased thrombus size as measured with a venous thrombosis model: thrombus size was increased by 50% with 1 mg/kg dexamethasone. No effects could be measured on the coagulation system, but it appeared that ex-vivo measured platelet aggregation was dose dependently inhibited by dexamethasone treatment. This effect resulted in-vivo in prolonged obstruction times as measured with a modified aorta-loop model. These results indicate that the expected prothrombotic state due to a diminished fibrinolytic activity caused by dexamethasone is counterbalanced by an inhibition of platelet aggregation.
van Giezen
J J
JJ
Solvay Duphar B. V., Dept. Vascular Pharmacology, Weesp, The Netherlands.
Jansen
J W
JW
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013924:Thrombophlebitis / Q000097:blood / Q000188:drug therapy; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy
D010975:Platelet Aggregation Inhibitors; D003907:Dexamethasone