Blood courses through our arteries and veins under pressure generated by our beating

heart. Consequently, an injury that cuts or punctures a vessel would result in rapid and

extensive loss of blood if there were no system to seal the injury. The blood clotting

system is the ‘first responder’ whose job it is to stem the loss of blood. Clotting is a

complex process that involves intertwined biochemical and biophysical subprocesses as

well as fluid dynamics and which results in the accumulation of blood platelets, the

generation of powerful enzymes, and the formation of a fibrous protein mesh that

together build the blood clot to staunch the continued loss of blood. The clotting system

can malfunction in one direction leading to formation of intravascular thrombi and

blockage of critical coronary or cerebral arteries. It can malfunction in the other

direction, failing to produce a clot adequate to prevent leakage of blood from the

vasculature. In the first part of this talk, I will sketch the models of arterial thrombosis

we are continuing to develop. These involve complex fluid dynamics, creation of an

evolving porous and elastic structure, and the issue of whether that structure remains

intact in the prevailing flow environment. In a second part of the talk, I will sketch a

different modeling effort that looks at the coagulation enzyme system which is central to

the clotting response. I will discuss what goes wrong in coagulation for persons with

severe hemophilia (a deficiency of an essential clotting protein). It is mysterious why

some persons with severe hemophilia have serious bleeding problems while others do

not. To probe this question, we used the model to generate over 100,000 synthetic

‘hemophilia patients’ in whom the concentrations of other clotting proteins spanned the

normal range (something not feasible with real patients), and we identified a surprising

correlation between one concentration and the overall response of the enzyme system

for hemophilia patients.