Thrombus Composition and the Evolving Role of Tenecteplase in Acute Ischemic Stroke

Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide, requiring rapid reperfusion to minimize damage. Current treatments, including intravenous thrombolysis (IVT) with alteplase (rt-PA) and mechanical thrombectomy (MT), face limitations such as thrombolysis resistance, dosing complexity, and reduced efficacy in large vessel occlusions (LVOs) or fibrin-rich clots. Tenecteplase (TNK), a bioengineered thrombolytic agent with superior pharmacokinetics, simplified administration, and higher fibrin specificity, offers promising advantages over rt-PA, including potential synergy with MT and efficacy against resistant thrombi. Direct oral anticoagulants (DOACs) further complicate AIS management, but evidence suggests that DOAC-treated patients may experience better thrombolysis outcomes due to distinct thrombus characteristics. Advances in imaging now enable precise visualization of vessel occlusion and treatment effects, opening opportunities to refine therapies. Combination approaches targeting fibrin thrombus components may enhance thrombolysis and improve outcomes in resistant cases. Future research should explore TNK's role in intra-arterial (IA) applications, combination therapies, and its interaction with MT to optimize reperfusion strategies. TNK's simplified use and promising efficacy position it as a potential breakthrough in AIS management, with the potential to improve functional recovery and reduce treatment complexity.