Improving fibrinolysis in venous thromboembolism: impact of fibrin structure

Introduction. Fibrinolysis is of key importance in maintaining vessel patency. Impaired fibrinolysis associated with more compact fibrin structure has been shown in patients with venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism (PE). Currently, recombinant or modified plasminogen activators are the only commonly available thrombolytic agents. However, they are fraught with side effects and suboptimal effectiveness. Areas covered. Based on the available literature, the current evidence linking fibrinolysis with VTE and potential therapeutic targets among fibrinolysis proteins are presented. Expert opinion. Prolonged clot lysis time has been reported as a new predictor of first-time and recurrent VTE, including PE. Anticoagulant therapy, including non-vitamin K antagonist oral anticoagulants, has a favorable impact on fibrinolysis in VTE patients. Several VTE risk factors are also related to lower efficiency of fibrinolysis and their treatment improve fibrinolysis, in part by alterations to fibrin properties. There is an increasing number of studies aiming at developing novel profibrinolytic therapeutic agents for treatment of VTE patients, mostly targeting the antifibrinolytic proteins, i.e. antiplasmin, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor.