Characterizing plasmin-induced lag phase and application of PDMS microfluidics to detection of fibrinolytic activity
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Physical trauma is responsible for over six million deaths annually, and of these roughly 40 percent result from acute traumatic coagulopathy (ATC) occurring in the first few hours of incidence. Patients who have developed ATC have significantly improved survivability when treated with tranexamic acid (TXA), a chemical inhibitor of the clot lysing enzyme plasmin. Current methods of detecting ATC are inadequate, lacking in either efficient speed, sensitivity, or cost. Hyperfibrinolysis (HF) is a key component of ATC and can be a result of excess plasmin activity. The following study observes effects of plasmin on hemostasis, and explores the use of silicon-based polydimethylsiloxane (PDMS) microfluidics measuring changes in electrical resistance as a method to detect HF. Coagulation was characterized by measuring turbidity of solutions containing fibrinogen and thrombin, and plasmin was incorporated to observe fibrinolysis and other plasmin-induced effects. It was found that high concentrations of plasmin caused a delay in the turbidity increase during coagulation. This lag phase may be a contributing factor to HF and ultimately ATC. Finally, the use of PDMS microfluidics to measure changes in electrical resistance to detect coagulation and fibrinolysis activity was supported. Resistance change adhered closely to traditional substrate-enzyme kinetics and plasmin-induced effects mimicked those which were observed in turbidity measurements. Further investment and development of this method of measurement could provide a faster, more accurate, and more inexpensive alternative to current techniques for measuring fibrinolysis.