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Published on: November 15, 2024
Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results
Yanan Wang1, Toshiki Maeda1, Shoujiang You1
1From the Department of Neurology (Y.W., S.W., M.L.), West China Hospital, Sichuan University, Chengdu, China; The George Institute for Global Health (Y.W., T.M., S.Y., C.C., L.L., Z.Z., C.D., J.P.C., C.S.A., X.C.), Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre (T.G.R.), Leicester, United Kingdom; University of Sydney (R.I.L.); Department of Clinical Medicine (C.D.), Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia; Division of Neuroimaging Sciences (G.M., J.M.W.), Centre for Clinical Brain Sciences and Centre in the UK Dementia Research Institute, University of Edinburgh, United Kingdom; Department of Neurology (J.P.C., C.S.A.), Royal Prince Alfred Hospital, Sydney Health Partners, Australia; Department of Preventive Medicine and Public Health (H.A.), Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Neurology Department (Y.H.), Peking University First Hospital, Beijing, China; Neurology Department (J.S.K.), Asan Medical Centre, Seoul, South Korea; Neurology and Psychiatry Department (P.M.L.), Clinica Alemana de Santiago, Facultad de Medicina Universidad del Desarrollo, Chile; Neurology Department (T.-H.L.), Chang Gung Memorial Hospital, Taipei, Taiwan; Neurology Department (C.L., M.W.P.), John Hunter Hospital and Hunter Medical Research Institute, Newcastle, Australia; Brazilian Stroke Network (S.C.M.), Hospital de Clínicas de Porto Alegre, Hospital Moinhos de Vento, Brazil; Neurology Department (J.D.P.), Christian Medical College, Ludhiana, India; Department of Neuroscience and Behavioral Sciences (O.M.P.-N.), Ribeirao Preto School of Medicine, Brazil; School of Medicine (V.K.S.), National University of Singapore and Division of Neurology (V.K.S.), National University Hospital, Singapore; Department of Cerebrovascular Disease (T.H.N.), 115 Hospital, Ho Chi Minh City, Vietnam; Shanghai Institute for Hypertension (J.W.), Rui Jin Hospital and Shanghai Jiaotong University; and Institute of Science and Technology for Brain-inspired Intelligence (C.S.A.), Fudan University, Shanghai, China.
Background And Objectives:
Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT.
Methods:
We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean).
Results:
Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system.
Discussion:
All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous.
Trial Registration Information:
ClinicalTrials.gov (NCT01422616).
