Thrombolysis is the FDA-approved pharmacological treatment for ischemic stroke when administered within 3 hours of symptom onset. It relies on tissue plasminogen activator (tPA) to convert plasminogen into plasmin, which proteolytically degrades fibrin fibers. Fibrin fibers are the polymeric scaffold that stabilizes clots and also serves as the substrate for tPA and plasminogen binding and their subsequent activation. Thus, fibrin structure is a critical determinant of plasminogen activation and thrombolytic efficiency. While differences between in vivo thrombi and in vitro clots have been extensively studied, the role of fibrin structure, a key determinant of clot stability and lysis, has been largely overlooked. Here, by using a combination of biophysical tools, including microfluidic channels, broadband anti-Stokes Raman scattering, and fluorescence imaging, we demonstrate that fibrin formed under arterial-like shear flow (∼1,500 s −1 ) undergoes structural alterations compared to fibers formed under static conditions. These changes significantly reduce tPA and plasminogen binding. This study provides fundamental insights into why thrombolysis is both time-dependent and often inefficient. Our findings identify fibrin structure as a critical translational target for improving stroke therapies.
Norouzi et al. (Sun,) studied this question.
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