Figure 5.

Current hyperfibrinolysis therapeutics and potential alternatives. Fibrin sealants are surgical haemostatic agents composed of a mix of pro-coagulation proteins, which ensure clot formation and prevents premature clot lysis. PolySTAT, a fibrin specific polymer with multiple fibrin domains, facilitates fibrin crosslinking while Chitosan, a biodegradable N-acetylglucosamine polymer, interacts with erythrocytes leading to erythrocyte agglutination. PolySTAT–Chitosan gauzes increase clot stability decreasing susceptibility to lysis. FXIII treatment results in fibrin crosslinking and crosslinking of PI to the fibrin network which improve clot stability and resistance to lysis. Solulin, a soluble form of thrombomodulin, acts by activating TAFI, which in turn cleaves lysine residues on fibrin preventing degradation of fibrin. Synthetic lysine analogues, TXA and EACA interact with plasmin(ogen) and block fibrin–plasmin(ogen) interactions, leading to increased resistance to clot lysis. More recently, Affimers, antibody mimetics raised against fibrinogen, were shown to interact with the fibrin, blocking plasmin-mediated degradation of the fibrin network. In vitro studies showed the potential use of Affimers in stabilizing the fibrin network and preventing premature lysis of the clot.