Intracranial Hemorrhage Associated With Revascularization Therapies

BACKGROUND AND PURPOSE: This review discusses the state of our current knowledge on hemorrhagic transformation (HT) and summarizes key factors to be considered when comparing risk associated with various approaches to revascularization. SUMMARY OF REVIEW: HT is a common and natural consequence of infarction, likely related to matrix metalloproteinases and free radical pathways disrupting permeability barriers between blood and brain during ischemia and reperfusion. Symptomatic HT rates within 24 to 36 hours of stroke are increased in the setting of revascularization therapy regardless of modality. HT incidence rates must be considered in the context of the timing of imaging, the period of the study, the definition of clinically significant HT, and other key predictors of HT. The most consistently identified predictors of clinically significant HT in acute revascularization trials have been thrombolytic therapy, dose of lytic agents, edema or mass effect on head CT, stroke severity, and age. Other risk factors may be hyperglycemia, concurrent heparin use, timing of therapy, and timing of successful recanalization. Future predictors may also include imaging parameters, serological markers, variables related to intra-arterial technique, and arterial lesion location. CONCLUSIONS: Understanding how baseline and treatment variables impact HT rates after acute stroke is critical for those designing and interpreting acute stroke trials. Future trials should consider the use of PH-2 as a standardized safety end point, putting hemorrhagic changes in the context of overall clinical outcome, and developing strategies to reduce the rates of clinically significant intracranial hemorrhage.