(1A) The intrinsic and (1B) extrinsic pathways converge into the (1C) common pathway. These pathways lead to the conversion of soluble fibrinogen to insoluble fibrin, catalyzed by thrombin. (2) Tissue plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA) converts plasminogen into plasmin. A healthy fibrinolytic system regulates the coagulation pathway and assists with successful lysis of the insoluble fibrin clot. (3) Plasmin cleaves fibrin into fibrin degradation products (FDPs), including D-dimer. (4) Protein C and thrombomodulin both regulate coagulation: thrombin binds to its receptor, thrombomodulin, resulting in activated protein C (APC). APC then inhibits both Va and VIIIa. (5) Dysregulated inflammatory molecules may interfere with tissue factor (TF) expression. (6) Dysregulated inflammatory molecules may also down-regulate thrombomodulin, resulting in hypercoagulation, as Va and VIIIa activities are then not sufficiently modulated. (7) In our laboraoty suty, we added Spike protein S1 to healthy plasma. Pathophysiology was noted in both prothrombin and fibrinogen chains. (8) Dysregulated inflammatory molecules in circulation can inhibit of the fibrinolytic system via up-regulation of plasminogen activator inhibitor-1 (PAI-1). PAI-I up-regulation interferes with tPA function, and ultimately results in a dysregulated coagulation system. (9) α2AP inhibits plasmin and ultimately will prevent sufficient fibrinolysis to happen. (Figure created with Biorender.com).