Molecular transport during fibrin clot lysis

Fibrin clot lysis is a dynamic process in which transport of fibrinolytic proteins plays an important role. Various recently established transport processes for plasminogen as well as for tissue-type and urokinase-type plasminogen activator (t-PA and u-PA, respectively) are reviewed.

During internal lysis of a plasma clot, plasminogen is translocated from the fluid phase to the surface of the lysing fibrin fibres. During external lysis, plasminogen strongly accumulates on the moving surface of the clot. In both types of lysis, binding takes place on C-terminal lysine residues in partially degraded fibrin that are generated by plasmin. The recently discovered thrombin activatable fibrinolysis inhibitor (TAFI) inhibits plasminogen binding by removing the C-terminal lysine residues. TAFI is a plasma carboxypeptidase B that is activated by thrombin and that links the coagulation system and the fibrinolytic system.

Transport of plasminogen activators is, in particular, essential for external clot lysis as it occurs during thrombolytic therapy. Because transport of proteins is not only mediated by diffusion, but also by fluid permeation, flow strongly promotes clot lysis. Penetration of plasminogen activators into clots is hampered by fibrin binding. While t-PA sticks to the surface of a clot, u-PA is able to enter a clot unhindered.

Recent studies show that ultrasound promotes plasminogen activator-induced clot lysis. A variety of mechanisms have been proposed to explain this promotion. Results indicate that an increased transport of fibrinolytic proteins significantly contributes to the acceleration of fibrinolysis by ultrasound.