Fibrinolysis: strategies to enhance the treatment of acute ischemic stroke

Abstract

Stroke is a major cause of disability worldwide, and is the second leading cause of death after ischemic heart disease. Until recently, tissue-type plasminogen activator (t-PA) was the only treatment for acute ischemic stroke. If administered within 4.5 h of symptom onset, t-PA improves the outcome in stroke patients. Mechanical thrombectomy is now the preferred treatment for patients with acute ischemic stroke resulting from a large-artery occlusion in the anterior circulation. However, the widespread use of mechanical thrombectomy is limited by two factors. First, only ⁓ 10% of patients with acute ischemic stroke have a proximal large-artery occlusion in the anterior circulation and present early enough to undergo mechanical thrombectomy within 6 h; an additional 9-10% of patients presenting within the 6-24-h time window may also qualify for the procedure. Second, not all stroke centers have the resources or expertise to perform mechanical thrombectomy. Nonetheless, patients who present to hospitals where thrombectomy is not an option can receive intravenous t-PA, and those with qualifying anterior circulation strokes can then be transferred to tertiary stroke centers where thrombectomy is available. Therefore, despite the advances afforded by mechanical thrombectomy, there remains a need for treatments that improve the efficacy and safety of thrombolytic therapy. In this review, we discuss: (i) current treatment options for acute ischemic stroke; (ii) the mechanism of action of fibrinolytic agents; and (iii) potential strategies to manipulate the fibrinolytic system to promote endogenous fibrinolysis or to enhance the efficacy of fibrinolytic therapy.

Novel antithrombotic strategies for treatment of venous thromboembolism

“…Inhibitors of activated TAFI (TAFIa) are being investigated for enhancement of endogenous fibrinolysis (Table 2). 65 When thrombin is generated, TAFI is activated by the thrombinthrombomodulin complex. TAFIa attenuates fibrinolysis by removing C-terminal lysine and arginine residues from partially degraded fibrin.…”

A review of the role of cav-1 in neuropathology and neural recovery after ischemic stroke

“…Since 2015, mechanical thrombectomy has become the first-line treatment for anterior circulation stroke with proximal large-artery occlusion. However, only about 20% of stroke patients have large-artery occlusion and it is a challenge to deliver treatment to them within the 24-h time window because the procedure can only be performed in highly specialized centers [6]. In general, for more patients who cannot accept thrombolysis or mechanical thrombectomy, it is essential to elucidate the molecular mechanisms underlying IS and explore potential therapeutic targets to restore function after stroke.…”

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

“…Ischemic stroke, which occurs suddenly due to thromboembolic occlusion of a major artery that supplies blood to the brain, represents the most common type and requires restoration of blood flow immediately. Thrombolytic agents and endovascular mechanical thrombectomy are the only treatment options to achieve recanalization with their limited therapeutic time window and side effects such as risk of hemorrhage [67]. On the other hand, hemorrhagic stroke occurs secondary to rupture and bleeding of a vessel in the brain and requires immediate surgery to remove clots and blood and decrease intracranial pressure [68].…”