Anticoagulation after Hemorrhagic Transformation in Acute Cardioembolic Ischemic Stroke

Translational Stroke Research (2026) 17:9 https://doi.org/10.1007/s12975-025-01397-3 RESEARCH Anticoagulation after Hemorrhagic Transformation in Acute Cardioembolic Ischemic Stroke Hyunsoo Kim1 · Ye-Eun An1 · Beom-Seok Seo1 · Jae-Myung Kim1 · Kang-Ho Choi1 · Man-Seok Park1 · Ji Sung Lee2 · Joon-Tae Kim1 Received: 29 April 2025 / Revised: 16 September 2025 / Accepted: 2 October 2025 / Published online: 26 December 2025 © The Author(s) 2025 Abstract To assess the association of anticoagulation in patients with cardioembolic acute ischemic stroke (CES) who develop hemorrhagic transformation (HT) and its impact on neuroimaging and functional outcomes. This retrospective study enrolled patients presenting with CES within 48 h at a tertiary stroke center between January 2011 and August 2023. Patients who developed HT during hospitalization and underwent follow-up imaging within 1 week were included, focusing on those with hemorrhagic infarction or parenchymal hematoma type 1. Primary outcomes were HT exacerbation on follow-up imaging and 3-month modified Rankin Scale (mRS) distribution shift, comparing anticoagulation therapy (AC), antiplatelet therapy (APT), and drug discontinuation (DDDD). The safety outcome was the occurrence of symptomatic intracerebral hemorrhage (sICH), which was defined as a hemorrhage concomitant with neurological deterioration. Among 763 patients with HT (age 74.6 ± 8.9 years, 48.1% male), AC was associated with a higher incidence of HT exacerbation compared to APT (adjusted OR 0.48, 95% CI 0.29–0.80, p-value = 0.005). AC associated with a better 3-month mRS compared to both APT (adjusted OR 0.63, 95% CI 0.43–0.92, p-value = 0.017) and DD (adjusted OR 0.38, 95% CI 0.26–0.55, p-value < 0.001). sICH occurred in 5%, with rates of 1.5%, 2.1%, and 11.7% in the AC, APT, and DD groups, respectively (adjusted OR for DD vs. AC: 3.93, 95% CI 1.18–13.16, p-value = 0.026). Anticoagulation in CES patients with HT was associated with a better functional outcome and radiological exacerbation, without a significant increase in sICH risk. These findings suggest that the presence of HT should not necessarily preclude the use of anticoagulation therapy in this patient population. However, our study should be interpreted as hypothesis-generating, and confirmation from future prospective studies is warranted. Keywords Hemorrhagic transformation · Anticoagulation · Acute ischemic stroke · Cardioembolism Introduction Hemorrhagic transformation (HT) is recognized as a natural phenomenon in the course of acute ischemic stroke and is frequently used as an indicator of clinical outcomes in Responsible Editor: Rajat Dhar. Joon-Tae Kim 1 Department of Neurology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea 2 Clinical Research Center, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea stroke patients [1]. Certain subtypes of HT, such as hemorrhagic infarction and parenchymal hematoma type 1, typically do not significantly affect neurological outcomes or mortality[2–4]. However, parenchymal hematoma type 2 is typically strongly associated with neurological deterioration and increased mortality rates [2–4]. Despite advancements in stroke management, HT remains a potentially prognostically detrimental complication, with reported incidence ranging from 13% to 46%[5, 6]. HT occurs more frequently and severely in acute cardioembolic stroke (CES) than in strokes of other etiologies. This is likely due to the distinct characteristics of CES. First, it often involves the sudden occlusion of a major cerebral artery by a large clot, which leads to a larger volume of acute ischemia. The subsequent restoration of blood flow into the ischemic territory—either spontaneously or 13 9 Page 2 of 10 following recanalization therapy—can cause more extensive hemorrhage due to the compromised integrity of alreadydamaged and weakened blood vessels. Additionally, CES is frequently associated with more severe underlying hypoperfusion, which contributes to greater infarct growth and, consequently, a higher risk of severe HT[6, 7]. Clinical guidelines on anticoagulation timing in CES aim to balance the risk of recurrent embolism against bleeding complications [8, 9]. These recommendations also emphasize tailoring the start of anticoagulation based on the likelihood of hemorrhagic conversion. Current guidelines acknowledge the presence of HT as an important factor in timing decisions but provide no specific recommendations, generally suggesting a 4–14 day delay based mainly on observational data [9]. In real-world practice, the presence of HT often leads clinicians to delay anticoagulation initiation; one study reported an average delay of 12 days, which was not associated with a higher risk of recurrent stroke [10]. In contrast to these practices, recent trials suggest early anticoagulation may have potential benefits over delayed therapy in atrial fibrillation patients with stroke [11–14]. However, most of these studies do not specifically address whether anticoagulation remains safe when HT is already present. Consequently, many clinicians are reluctant to administer anticoagulation once HT has been detected, given the lack of robust evidence evaluating its safety in an ongoing hemorrhagic process [15–17]. The presence of HT, therefore, is also a crucial factor to consider when determining the most appropriate timing to initiate medication. The lack of comprehensive data is compounded by the fact that existing studies are primarily based on small patient cohorts or subgroup analyses, making it difficult to draw definitive conclusions or establish clear clinical guidelines [18, 19]. To address this critical knowledge gap, our study aims to investigate the impact of anticoagulation on HT exacerbation, as visualized on follow-up imaging, and on clinical outcomes in patients with CES. We have specifically excluded patients with parenchymal hematoma type 2 from our analysis, given its well-established association with poor neurological outcomes. By focusing on patients with less severe forms of HT, we aim to challenge the prevailing guideline recommendation to delay anticoagulation in this population, while providing more nuanced insights into the safety and optimal timing of therapy. Subjects/Materials and Methods Subjects This retrospective study included patients with acute ischemic stroke who presented within 48 h of symptom onset at 13 Translational Stroke Research (2026) 17:9 a tertiary stroke center between January 2011 and August 2023 (n = 12,658). Among them, CES was classified per the Trial of Org 10,172 in Acute Stroke Treatment criteria [20], based on the attending physician’s clinical and radiological judgement (n = 2,820).Only patients who developed HT based on imaging performed during hospitalization were included (n = 1,050). Those for whom changes in HT could not b (...truncated)