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Abstract
A model of fibrinolysis was developed using multicomponent convection-diffusion equations
with homogeneous reaction and heterogeneous adsorption and reaction. Fibrin is the
dissolving stationary phase and plasminogen, tissue plasminogen activator (tPA), urokinase
(uPA), and plasmin are the soluble mobile species. The model is based on an accurate
molecular description of the fibrin fiber and protofibril structure and contains no
adjustable parameters and one phenomenological parameter estimated from experiment.
The model can predict lysis fronts moving across fibrin clots (fine or coarse fibers)
of various densities under different administration regimes using uPA and tPA. We
predict that pressure-driven permeation is the major mode of transport that allows
for kinetically significant thrombolysis during clinical situations. Without permeation,
clot lysis would be severely diffusion limited and would require hundreds of minutes.
Adsorption of tPA to fibrin under conditions of permeation was a nonequilibrium process
that tended to front load clots with tPA. Protein engineering efforts to design optimal
thrombolytics will likely be affected by the permeation processes that occur during
thrombolysis.