Mass transfer regulation of coagulation

Plasma perfused over a spots of 800 nm silica beads coated with lipidated tissue factor at 50 1/s for 10 min. Top. Fluorescent images of accumulation of fibrin as a function of shear rate. Bottom. Electron micrographs showing the reduction in fiber diameter with increasing shear rate.

One example where fluid and solute transport affect clot formation is in the assembly of fibrin.  The conversion of fibrinogen to fibrin by the enzyme thrombin is the final reaction of the coagulation cascade.  Fibrin fibers are the scaffold onto which a blood clot is built.  We have found that there exists a balance between the kinetics of fibrin assembly and transport of reactants away from the vessel wall.  It turns out that the morphology of fibrin fibers can be predicted by two dimensionless quantities (Peclet and Dahmkohler numbers) that describe the relative rates of transport and reaction. Fluid and solute in the interstitial spaces has been hypothesized as a biophysical regulator of clot growth. In our experiments we have found a sharp transition in fluid permeability and solid mechanics the volume fraction of fibrin fibers exceeds 0.1 

Related Publications

A.A. Onasoga-Jarvis, T.J. Puls, S.K. O’Brien, L Kuang, H.J. Liang, K.B. Neeves. Thrombin generation and fibrin formation under flow on biomimetic tissue factor rich surfacesJournal of Thrombosis and Haemostasis,12 (2014): 372-382. PMID: 24345079

A.A. Onasoga-Jarvis, K. Leiderman, A.L. Fogelson, M. Wang, M.J. Manco-Johnson, J.A. Di Paola, K.B. Neeves. The effect of factor VIII deficiencies and replacement and bypass therapies on thrombus formation under venous flow conditions in microfluidic and computational models. PLoS One, 8 (2013): e78732. PMID: 24236042

A.R. Wufsus, N.E. Macera, K.B. Neeves. The hydraulic permeability of blood clots as a function of fibrin and platelet density. Biophysical Journal, 104 (2013): 1812-1823. Featured in New and Notable editorial. PMID: 23601328

K.B. Neeves, A.A. Onasoga, R.R. Hansen, J.J. Lilly, D. Venckunaite, M.B. Sumner, A.T. Irish, G. Brodsky, M.J. Manco-Johnson, J.A. Di Paola. Sources of variability in platelet accumulation on type I fibrillar collagen in microfluidic flow assays. PLoS One, 8 (2013): e54680, doi:10.1371/journal.pone.0054680. PMID: 23355889

K.B. Neeves, D.A.R. Illing, S.L. Diamond.  Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow.  Biophysical Journal, 98 (2010), 1344-1352. PMID: 20371335