Dependence of clot structure and fibrinolysis on apixaban and clotting activator

<strong style="background-color:rgb(255, 255, 255);color:rgb(33, 33, 33);">Background: &lt;/strong&gt;Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow. Fibrinolysis is initiated when tissue plasminogen activator (tPA) converts plasminogen to plasmin, which binds to and degrades a fibrin fiber. The effects of apixaban on clot structure and lysis have been incompletely studied.</strong><strong style="background-color:rgb(255, 255, 255);color:rgb(33, 33, 33);">Objectives: &lt;/strong&gt;We aimed to study apixaban effects on clot structure, kinetics, and fibrinolysis using thrombin (low or high concentration) or tissue factor (TF) to activate clot formation.</strong><strong style="background-color:rgb(255, 255, 255);color:rgb(33, 33, 33);">Methods: &lt;/strong&gt;We used a combination of confocal and scanning electron microscopy and turbidity to analyze the structure, formation kinetics, and susceptibility to lysis when plasma was activated with low concentrations of thrombin, high concentrations of thrombin, or TF in the presence or absence of apixaban.</strong><strong style="background-color:rgb(255, 255, 255);color:rgb(33, 33, 33);">Results: &lt;/strong&gt;We found that the clotting activator and apixaban differentially modulated clot structure and lytic potential. Low thrombin clots with apixaban lysed quickly due to a loose network and FXa cleavage product's cofactor with tPA; high thrombin clots lysed faster due to FXa cleavage product's cofactor with tPA; TF generated loose clots with restricted lysis due to their activation of thrombin activatable fibrinolytic inhibitor.</strong><strong style="background-color:rgb(255, 255, 255);color:rgb(33, 33, 33);">Conclusion: &lt;/strong&gt;Our study elucidates the role of apixaban in fibrinolytic pathways with different clotting activators and can be used for the development of therapeutic strategies using apixaban as a cofactor in fibrinolytic pathways.</strong>