title: Thrombin generation and fibrin formation under flow on biomimetic tissue factor-rich surfaces.
abstract: BACKGROUND
  Blood flow regulates coagulation and fibrin assembly by controlling the rate of transport of zymogens, enzymes and plasma proteins to and from the site of an injury.
  
  
  OBJECTIVE
  The objective of this work was to define the hemodynamic conditions under which fibrin can form under flow on tissue factor (TF)-rich substrates.
  
  
  METHODS
  TF-coated silica beads (~ 800 nm) were patterned into 18-85-μm spots. Normal pooled plasma and factors VIII, IX and XI deficient plasmas were perfused over the beads coated with 0.08, 0.8 and 8 molecules-TF μm(-2) at shear rates of 50-1000 s(-1) . Fibrin deposition and thrombin generation were measured by fluorescence microscopy in a hydrodynamic focusing microfluidic device.
  
  
  CONCLUSIONS
  Fibrin deposition was supported on patterned bead spots, but not planar TF substrates at the same surface TF concentration. There was a threshold spot size and a shear rate dependent TF concentration that was necessary to support fibrin polymerization. FVIII and FIX had minor effects on fibrin dynamics at 8 molecules-TF μm(-2) , but were essential at 0.8 molecules-TF μm(-2) . The absence of FXI influenced thrombin generation and fibrin deposition at both 0.8 and 8 molecules-TF μm(-2) . These results show that fibrin deposition requires perturbations in the flow field that protect reactions from dilution by flow under venous and arterial conditions. FVIII and FIX have a modest effect on fibrin deposition at high TF concentrations, but are necessary for fibrin deposition at low TF concentrations. FXI amplifies thrombin generation under flow at both low and high TF concentrations.
authors.affiliation: Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Onasoga-Jarvis
authors.forename: T J
authors.initials: TJ
authors.lastname: Puls
authors.forename: S K
authors.initials: SK
authors.lastname: O'Brien
authors.forename: L
authors.initials: L
authors.lastname: Kuang
authors.forename: H J
authors.initials: HJ
authors.lastname: Liang
authors.forename: K B
authors.initials: KB
authors.lastname: Neeves
mesh_terms: D032701:Biomimetics / Q000379:methods*; D001777:Blood Coagulation; D002448:Cell Adhesion; D004792:Enzyme Precursors / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry*; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D006439:Hemodynamics; D006801:Humans; D057446:Hydrodynamics; D007091:Image Processing, Computer-Assisted; D008051:Lipid Bilayers / Q000737:chemistry; D046210:Microfluidic Analytical Techniques; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D033081:Shear Strength; D012822:Silicon Dioxide / Q000737:chemistry; D013917:Thrombin / Q000737:chemistry*; D013925:Thromboplastin / Q000737:chemistry
chemical_list: D004792:Enzyme Precursors; D005338:Fibrin Fibrinogen Degradation Products; D008051:Lipid Bilayers; C036309:fibrin fragment D; D012822:Silicon Dioxide; D005337:Fibrin; D013925:Thromboplastin; D013917:Thrombin
keywords: blood coagulation; fibrin; hemodynamics; thrombin; thromboplastin