7 The distinction between thrombus contraction and clot retraction is salient, as fibrinogen, von Willebrand factor, and fibrin are structurally and functionally distinct molecules that undergo different regulatory processes. Thrombus contraction is a fibrin-independent process that occurs during the early stages of platelet aggregation and thrombus formation 7, 8 and is an important means of facilitating primary hemostatic plug formation. ![]() The platelet contractile machinery affects thrombus packing in 2 distinct ways: “thrombus contraction,” where contractile forces are transduced through a network of fibrinogen/von Willebrand factor–bound platelets, 7-9 and “clot retraction,” where contractile forces are transmitted through a network of fibrin-bound platelets. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size. These effects correlated with changes in the elastic modulus of fibrin clots. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa–mediated platelet contractility prevented shrinkage of the fibrin network. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. ![]() ![]() Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. ![]() This process is considered important for promoting clot stability and maintaining blood vessel patency. Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size.
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