Hi Jesse,
"It would be like a city having no entry areas for the police or firetrucks . . ." -- You've not visited LA or New Orleans??
Kidding aside, for all of our economic sakes, I'm hoping you are right.
And were I a betting man (please god lets not re-kindle that thread :)), I'd bet you are right. In fact, substantial amounts of my money are placed on my suspicion that if receptors are present in a system, the evolutionary efficiency of physiology would make it more likely than not that receptor agonists are there as well.
My primary point though (in a fit of intellectual honesty), is that we have NO direct proof of this, and one of the humans most likely to have direct knowledge of this (Dr. Ruf) didn't take ATIII's activity in the lymphatics as inevitable either.
I know you are in practice, but just so others don't get confused, the direct thrombin blocker the Nature paper authors used was hirudin (not Xigris).
Just because it is funny (if a somewhat pathetic place to me in when marketing a very expensive drug), I've copied the below from the first page of the Lilly site for Xigris, where they (are honest enough to state): "The specific mechanisms by which Xigris exerts its effect on survival in patients with severe sepsis are not completely understood."
The good news for us all is that when ATIII is marketed successfully for the same indication (sepsis/DIC), they won't have to make this same pathetic disclaimer, and will simply quote the Nature PAR1 and the J. Thromb. paper!
Best Regards,
MTB
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