Cerebral hemorrhage after intravenous alteplase treatment in acute ischemic stroke: A single center retrospective study

Aim: Although alteplase, a recombinant tissue plasminogen activator (rt-PA), is an effective treatment for acute ischemic stroke, cerebral hemorrhage, an uncommon but serious complication, may occur after alteplase treatment. The aim of this study was to determine the factors affecting the development of cerebral hemorrhages, especially symptomatic cerebral hemorrhage, after intravenous (IV) alteplase treatment with a diagnosis of acute ischemic stroke, to develop strategies for the management of these patients and to contribute to other studies on this subject. Method: Between April 2007 and April 2022, 679 patients who were diagnosed with acute ischemic stroke and given IV alteplase treatment in the emergency department of Karadeniz Technical University (KTU) Farabi Hospital were retrospectively analyzed and 111 patients who developed cerebral hemorrhage within 48 hours after the treatment were included in the study. The clinical, demographic, radiographic and risk factors of the patients included in the study were examined. Cerebral hemorrhages causing an increase of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) value were accepted as symptomatic cerebral hemorrhage, and the relationship of these factors with symptomatic cerebral hemorrhage was evaluated. Heidelberg classification of bleeding was used to identify cerebral hemorrhage types. Results: Of 679 patients who received IV alteplase, cerebral hemorrhage developed within 48 hours after treatment in a total of 111 (%16,3) patients, 30 (%4,4) of whom were symptomatic and 81 (%11,9) of whom were asymptomatic. Hemorrhagic infarction with confluent petechiae (1b) developed in 25 patients (%23,6) with the highest rate. Fatal cerebral hemorrhage was observed in 6 patients (%5,4). When age was grouped as ≤80 and >80; ≤60, 61-70, 71-80 and >80, no significant difference was found between these age groups in terms of the development of symptomatic cerebral hemorrhage (p values 0,970, 0,991, respectively). No significant difference was found between genders in terms of the development of symptomatic cerebral hemorrhage (p= 0,851). Symptomatic cerebral hemorrhage developed in 3 (%18,8) patients with an NIHSS value between 0-4, 13 (%23,2) patients with an NIHSS value between 5-10, 11 (%50) patients with an NIHSS value between iv 11-15, and 3 (%20) patients with an NIHSS value between 16-21. Although statistical significance was not determined, it was found that the rate of symptomatic cerebral hemorrhage increased as the NIHSS value increased between 0-15 and decreased again between 16-21. Symptomatic cerebral hemorrhage developed in 3 (%50) patients with a symptom-injection time of 90 min, 19 (%35,2) patients with a symptom-injection time of 91-180 min, and 7 (%14,9) patients with a symptom-injection time of 181-270 min. Symptomatic cerebral hemorrhage developed in 4 (%40) patients with signs of early infarction and 26 (%25,7) patients without signs of early infarction before alteplase treatment. Although there was no statistically significant difference, symptomatic cerebral hemorrhage developed at a higher rate in patients with signs of early infarction (p=0,455). There was no significant difference in the development of symptomatic cerebral hemorrhage between patients with and without a history of leukaryosis, prior antiaggregant/anticoagulant use, previous ischemic stroke, diabetes, hypertension, atrial fibrillation (AF), ischemic heart disease and heart failure (p values 1,000, 0,799, 1,000, 0,726, 0,989, 0,361, 0,857, 1,000, respectively). Symptomatic cerebral hemorrhage developed in 4 (%66,7) patients with a history of renal failure and in 26 (%24,8) patients without renal failure, and the rate of symptomatic cerebral hemorrhage was found to be significantly higher in patients with renal failure (p=0,045). Symptomatic cerebral hemorrhage developed in 2 (%22,2) smokers and 3 (%37,5) non-smokers. Although statistical significance could not be determined, it was observed that symptomatic cerebral hemorrhage developed at a lower rate in smokers. Conclusion: In our study, no significant association was found between most clinical, demographic, radiographic and risk factors and the development of symptomatic cerebral hemorrhage after alteplase treatment in acute ischemic stroke patients. However, these factors have been shown to increase symptomatic cerebral hemorrhage in studies. Although these factors increase the development of postthrombolytic symptomatic cerebral hemorrhage, which can be an important cause of morbidity and mortality, alteplase treatment has been proven to be effective in acute ischemic stroke and should be administered promptly to stop tissue damage and reperfusion in appropriate acute ischemic stroke patients.