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Thrombin generation and fibrin formation under flow on biomimetic tissue factor‐rich surfaces
Author(s) -
OnasogaJarvis A. A.,
Puls T. J.,
O'Brien S. K.,
Kuang L.,
Liang H. J.,
Neeves K. B.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12491
Subject(s) - fibrin , thrombin generation , thrombin , tissue factor , chemistry , flow (mathematics) , microbiology and biotechnology , biomedical engineering , biophysics , medicine , immunology , biology , coagulation , platelet , mechanics , physics
Summary 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. Results and 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.