Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review

Reperfusion therapies by tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) have ushered in a new era in the treatment of acute ischemic stroke (AIS). However, reperfusion therapy-related HT remains an enigma. To provide a comprehensive review focused on emerging concepts of stroke and therapeutic strategies, including the use of protective agents to prevent HT after reperfusion therapies for AIS. A literature review was performed using PubMed and the ClinicalTrials.gov database. Risk of HT increases with delayed initiation of tPA treatment, higher baseline glucose level, age, stroke severity, episode of transient ischemic attack within 7 days of stroke onset, and hypertension. At a molecular level, HT that develops after thrombolysis is thought to be caused by reactive oxygen species, inflammation, remodeling factor-mediated effects, and tPA toxicity. Modulation of these pathophysiological mechanisms could be a therapeutic strategy to prevent HT after tPA treatment. Clinical mechanisms underlying HT after MT are thought to involve smoking, a low Alberta Stroke Program Early CT Score, use of general anesthesia, unfavorable collaterals, and thromboembolic migration. However, the molecular mechanisms are yet to be fully investigated. Clinical trials with MT and protective agents have also been planned and good outcomes are expected. To fully utilize the easily accessible drug—tPA—and the high recanalization rate of MT, it is important to reduce bleeding complications after recanalization. A future study direction could be to investigate the recovery of neurological function by combining reperfusion therapies with cell therapies and/or use of pleiotropic protective agents. •Reperfusion therapy-related hemorrhage remains an enigma.•We review the therapeutic strategies to prevent hemorrhage after reperfusion for AIS.•Effects of combination therapy with pleiotropic agents and tPA have been investigated.•Hemorrhagic risk in thrombectomy may be lower than that with tPA treatment alone.•Combined reperfusion therapies with cell therapies and/or pleiotropic protective agents might be useful.