The final step in the characterization of C22G1 self-assembled dendrimers as potential protamine replacers was the determination of their ability to reverse the coagulation inhibition induced by heparin. As we know, blood coagulation is an exceedingly complex process [37] which, for the sake of brevity, can be simplified and condensed as follows. After any blood vessel endothelial injury, platelets (aka thrombocytes) quickly gather at the lesion site and create a cross-linked plug (primary hemostasis). This, in turn, activates the so-called coagulation cascade, with resultant fibrin deposition and linking (secondary hemostasis). Platelets retraction and inhibition, followed by wound repair, complete the process. For diagnostic/prognostic purposes, the clotting cascade is assumed to consist of two separate yet interactive pathways: The intrinsic pathway, activated by the external trauma that causes blood to leave the vascular system and involves factor VII; and the extrinsic pathway, which originates by the trauma within the vascular system, is activated by platelets, exposed endothelium, chemicals, or collagen, and involves factors XII, XI, IX, and VIII. Typically, the intrinsic route is quantified by the activated partial thromboplastin time (aPTT) assay, which measures the time required by the complex formed among various plasma clotting factors (called thromboplastin) to convert prothrombin to thrombin and, hence, generate the fibrin clot. The extrinsic pathway, on the other hand, is routinely monitored by the prothrombin clotting time (PT) assay, a one-stage test based upon on the time required for a fibrin clot to form after the addition of tissue factor (TF, aka called platelet tissue factor, factor III, or CD142, an integral transmembrane receptor for Factor VII/VIIa), phospholipid, and calcium to decalcified, platelet-poor plasma.