Hemorrhagic Transformation After Ischemic Stroke: Mechanisms and Management

 So we need research on preventing hemorrhagic transformation. WHOM is going to do that? Specific names only. With NO stroke leadership or strategy NOTHING WILL OCCUR.

Ji Man Hong^1,2*, Da Sol Kim² and Min Kim¹

• ¹Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon-si, South Korea
• ²Department of Biomedical Science, Ajou University School of Medicine, Ajou University Medical Center, Suwon-si, South Korea

Symptomatic hemorrhagic transformation (HT) is one of the complications most likely to lead to death in patients with acute ischemic stroke. HT after acute ischemic stroke is diagnosed when certain areas of cerebral infarction appear as cerebral hemorrhage on radiological images. Its mechanisms are usually explained by disruption of the blood-brain barrier and reperfusion injury that causes leakage of peripheral blood cells. In ischemic infarction, HT may be a natural progression of acute ischemic stroke and can be facilitated or enhanced by reperfusion therapy. Therefore, to balance risks and benefits, HT occurrence in acute stroke settings is an important factor to be considered by physicians to determine whether recanalization therapy should be performed. This review aims to illustrate the pathophysiological mechanisms of HT, outline most HT-related factors after reperfusion therapy, and describe prevention strategies for the occurrence and enlargement of HT, such as blood pressure control. Finally, we propose a promising therapeutic approach based on biological research studies that would help clinicians treat such catastrophic complications.

Introduction

Hemorrhagic transformation refers to hemorrhagic infarction that occurs after venous thrombosis or arterial thrombosis and embolism (1, 2). Autopsy studies have reported an HT rate of 18–42% in acute ischemic stroke due to arterial occlusion (1, 3). The frequency of HT has been reported mainly in clinical studies using brain imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), rather than pathological studies (4). Therefore, prior to considering the frequency of occurrence of HT, we need to understand the imaging and clinical definitions of HT. Although rates of HT in ischemic stroke have been reported, more than half of all cerebral infarctions demonstrate certain stages of HT (5).

The radiographic definition of HT is generally classified by the European Cooperative Acute Stroke Study (ECASS) (6). On CT scans, the severity of HT is divided into two stages: hemorrhagic infarction (HI) and parenchymal hemorrhage (PH) with or without mass effect. Each stage is divided into two subtypes (7). Each characteristic is presented in Table 1 (8).

TABLE 1

Table 1. Characteristics of hemorrhagic transformation (HT) according to European Cooperative Acute Stroke Study (ECASS) 2 (8).

With recent advances in intravenous (9) or endovascular (10) reperfusion therapies for acute ischemic stroke (11), stroke physicians need to deepen their understanding of cerebral hemorrhagic complications. Although the overall risks of complications have been well-documented in various randomized controlled trials (RCTs) of reperfusion therapies (12), the mechanisms underlying cerebral hemorrhage or hematoma after stroke in individual patients remain poorly understood. Intracranial bleeding after acute ischemic stroke has a significant impact on patient outcomes (13, 14), and controlling the risk of bleeding plays an important role in determining whether to proceed with recanalization (15). Large parenchymal hematomas and symptomatic intracerebral hemorrhage (sICH) are the most feared, tend to have a high mortality rate, and appear in up to 6% of patients after intravenous thrombolysis (16). In addition, infarction evolution with HT can lead to significant neurological deterioration (17–19). The frequency of HT is associated with different factors, such as epidemiological factors (e.g., age, pre-stroke treatment, and conditions), characteristics of the infarct (size of ischemic core and timing of follow-up), reperfusion techniques in the acute phase (intravenous thrombolysis, mechanical thrombectomy, or combined), radiological diagnosis (CT or MRI techniques), and use of antithrombotics after the acute phase (20–22).