Analysis of blood clot degradation fragment sizes in relation to plasma flow velocity

Thrombolytic therapy aims to dissolve blood clots and restore vessel patency. Our hypothesis is that the therapy depends not only on chemical reactions of the fibrinolytic system, but also on mechanical forces exerted by streaming blood on the clot surface. The aim of the study was to analyze the role of mechanical forces in promoting thrombolysis and their relation to the maximum size of removed clot fragments. Non-occlusive whole-blood clots were exposed to flow of plasma containing the thrombolytic agent rt-PA. Plasma, perfusing through the clot, was collected and the sizes of clot degradation fragments in the plasma were analyzed by optical microscopy. Theoretical models for the maximum clot fragment size as a function of blood flow velocity were developed based on the relation between surface or volume clot binding forces and the opposing forces of the streaming plasma in the laminar or turbulent flow regime. The best agreement between experimental results and models was obtained for the volume binding forces and the laminar flow model, in which the maximum clot fragment size was linearly dependent on the plasma flow velocity. Such result could not be obtained if thrombolysis would be purely a biochemical process. Therefore, the result confirms our hypothesis that thrombolysis is also strongly influenced by the mechanical forces of streaming plasma.