Thrombolytic resistance: an important factor leading to the failure of intravenous thrombolytic therapy

Acute ischemic stroke (AIS) is one of the most common nervous system diseases. Its high mortality and disability rates not only seriously threaten patients' health but also impose a significant socioeconomic burden. Intravenous thrombolysis (IVT) is the first-line treatment for AIS, and tissue-type plasminogen activator (t-PA) is the primary agent used in IVT. With the extension of the therapeutic time window, more AIS patients are eligible to receive t-PA treatment. The existence of thrombolytic resistance severely compromises the clinical efficacy of t-PA in AIS treatment. This paper elaborates on the phenomenon of thrombolytic resistance and analyzes the roles of thrombus components such as red blood cells (RBCs), platelets (PLTs), white blood cells (WBCs), and neutrophil extracellular traps (NETs), as well as non-thrombotic factors such as metabolic syndrome (MetS) and fatty acid (FA) in contributing to thrombolytic resistance. By clarifying the underlying mechanisms of thrombolytic resistance, this work aims to provide insights for strategies to overcome thrombolytic resistance and improve the therapeutic efficacy of t-PA.