Ischemic stroke represents one of the leading causes of mortality and long-term disability worldwide. Despite the widespread clinical use of enzymatic thrombolysis with recombinant tissue plasminogen activators (alteplase or tenecteplase), its efficacy remains limited and exhibits considerable interindividual variability. The outcome of thrombolytic therapy is influenced not only by the intrinsic characteristics of the clot but also by the dynamics of the fibrinolytic system, particularly the availability of plasminogen, whose progressive depletion may limit further fibrin degradation. Increasing experimental and clinical evidence indicates that the structural, compositional, and mechanical properties of the clot play a critical role in determining therapeutic efficacy.
This thesis focuses on investigating the impact of clot structural variability on the efficiency of enzymatic thrombolysis under in vitro conditions. Model clots with a defined microstructure were prepared and subsequently characterized using histological methods and mechanical property analysis. The lytic efficacy of selected thrombolytic agents (alteplase, staphylokinase, and urokinase) was evaluated in relation to clot structure, while simultaneously assessing the effect of plasminogen availability during the thrombolytic process.
The results demonstrate that clot microstructure fundamentally influences thrombolytic efficacy. Fibrin- and platelet-rich clots exhibit increased resistance to lysis due to their compact structure and limited permeability, whereas clots with a higher red blood cell content are more susceptible to enzymatic degradation. In addition, a marker for in vitro systems enabling the assessment of thrombolysis activation was established. These findings contribute to a deeper understanding of the mechanisms underlying enzymatic thrombolysis and highlight the importance of considering clot characteristics when optimizing thrombolytic therapy.