This study was designed to assess the effect of
Factor Xa antagonists on
thrombus formation at various axial positions on a
tissue factor rich surface under arterial blood flow conditions. Non-anticoagulated, flowing human blood, drawn directly from an antecubital vein, was perfused over a
tissue factor coated cover slip in a parallel-plate perfusion chamber.
Thrombus surface coverage,
thrombus mean height and
fibrin surface coverage were measured at six different axial positions by confocal microscopy. Both
thrombus surface coverage and mean height decreased along the cover slip axis whereas the
fibrin surface coverage increased. Pre-chamber treatment of blood with the
direct Factor Xa inhibitors Razaxaban and 813893 resulted in significantly reduced
thrombus and
fibrin formation at all axial positions investigated (P < 0.05).
Thrombus and
fibrin deposition in a laminar flow chamber changed with axial position with surface coverage measurements being more reproducible than
thrombus mean height. Data were more reproducible towards the centre of the flow chamber than at the extremities.
Razaxaban and 813893 inhibited
thrombus and
fibrin formation at the highest concentrations tested. No difference in
drug effect was apparent at different axial positions. In conclusion, axial position influences the degree of
thrombus and
fibrin deposition with measurements being less reproducible at the extremities of the flow chamber. This technique may prove useful for analysing anti-thrombotic
drug effects before progression to clinical trials.