Recombinant soluble human thrombomodulin: a randomized, blinded assessment of prevention of venous thrombosis and effects on hemostatic parameters in a rat model.
Thrombomodulin is an endothelial surface receptor that binds thrombin and accelerates the activation of protein C. We compared the effects of a recombinant thrombomodulin analog (TME), recombinant hirudin (r-HIR), heparin sodium (HEP), and normal saline (Control) on thrombus formation, activated partial thromboplastin time (APTT), thrombin time (TT), platelet aggregation and tail transection bleeding time (BT) in a rat model of vena cava thrombosis.


RESULTS
TME, r-HIR and HEP prevented venous thrombosis in this model in a dose-dependent manner. At the dose required to reduce vena cava thrombosis by 50% (ED50), TME did not prolong the APTT or TT as did HEP and r-HIR. Platelet aggregation in response to thrombin was not effected by TME but was inhibited by both r-HIR and HEP. BT did not differentiate the agents tested.


CONCLUSIONS
TME inhibited venous thrombosis in a rat vena cava model with less effect on hemostatic variables than HEP or r-HIR.
Solis
M M
MM
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock.
Vitti
M
M
Cook
J
J
Young
D
D
Glaser
C
C
Light
D
D
Morser
J
J
Wydro
R
R
Yu
S
S
Fink
L
L
D000818:Animals; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000627:therapeutic use; D024764:Hirudin Therapy; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D012995:Solubility; D018180:Thrombomodulin; D013927:Thrombosis / Q000517:prevention & control*; D014682:Vena Cava, Inferior
D011994:Recombinant Proteins; D018180:Thrombomodulin; D006493:Heparin