A State-of-the-Art Review published on Feb. 26 in JACC: Basic to Translational Science highlights the potential of emerging thrombolytic therapies such as antagonists of fibrinolysis inhibitors to improve safety and efficacy of the treatment and prevention of acute thrombosis in patients with venous thromboembolism (VTE).

According to Satish Kumar Singh, MD, PhD, et al., standard treatment for VTE with current anticoagulants and fibrinolytic agents has drawbacks, including incomplete resolution, recurrent thrombosis and risk of serious bleeding complications. In their review, they discuss the mechanisms of venous thrombus aging, where the "acute, fibrin and red blood cell-rich composition changes to a chronic cellular, fibrotic mass." Once chronic, the condition no longer responds to presently available treatment options.

"More research insights are needed into the mechanisms responsible for the acute-to-chronic transition of venous thrombi to support treatment innovations that are appropriately targeted to thrombus age," note the authors.

Latest developments in pharmocotherapeutic approaches for VTE are outlined with anticoagulation covered as first-line therapy. The authors then explore thrombolytic therapy, including its historically unacceptable bleeding risks and more recent efforts to reduce bleeding complications and extend the treatment to lower-risk patients.

"A novel therapeutic paradigm is now emerging that venous thrombi can be safety dissolved without significantly increased bleeding by targeting fibrinolysis inhibitors such as [alpha2-antiplasmin (α2AP)], [plasminogen activator inhibitor (PAI)]-1 and thrombin activable fibrinolysis inhibitor," state the authors.

Antiplatelet and anti-inflammation approaches are also discussed as well as treatment approaches for chronic complications of VTE like postpulmonary embolism impairment, post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension.