Abstract

The prevalence and risk factors of hemorrhagic transformation (HT) after acute ischemic stroke HT have not been adequately delineated. We performed a systematic review and meta-analysis to identify English-language prospective observational MEDLINE and EMBASE-listed reports of acute ischemic stroke with HT published from 1985–2017. Studies that used the ECASS-2 definitions of hemorrhagic transformation subtypes, hemorrhagic infarction (HI), and parenchymal hematoma (PH) were included. Patients treated with intravenous thrombolysis with tissue plasminogen activator (IV-tPA) were compared with those who did not receive thrombolysis. A total of 65 studies with 17,259 patients met inclusion criteria. Overall, HT prevalence was 27%; 32% in patients receiving IV-tPA vs. 20% in those without. Overall PH prevalence was 9%; 12% in IV-tPA treated patients vs. 5% in those without. HT was associated with a history of atrial fibrillation (OR 2.94) and use of anticoagulants (OR 2.47). HT patients had higher NIHSS (Hedge’s-G 0.96) and larger infarct volume (diffusion-weighted MRI, Hedge’s-G 0.8). In IV-tPA treated patients, PH correlated with antiplatelet (OR 3) and statin treatment (OR 4). HT (OR 3) and PH (OR 8) were associated with a poor outcome at 90-day (mRS 5–6). Hemorrhagic transformation is a frequent complication of acute ischemic stroke and is associated with poor outcome. Recognition of risk factors for HT and PH may reduce their incidence and severity.

Highlights

  • Hemorrhagic transformation (HT) occurs frequently in patients with acute ischemic stroke

  • There are two accepted classification schemes for HT assessment; one is based strictly on radiological criteria, while the second combines both clinical and radiological variables. The former was used as a safety end point for intravenous thrombolysis with tissue plasminogen activator (IV-tPA)-related HT in the European Cooperative Acute Stroke Trials (ECASS) [3–5]

  • As rates of HT are higher in patients treated with IV-tPA [9], we investigated interactions between possible predictors of HT in IV-tPA treated and untreated subpopulations

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Summary

Introduction

Hemorrhagic transformation (HT) occurs frequently in patients with acute ischemic stroke. There are two accepted classification schemes for HT assessment; one is based strictly on radiological criteria, while the second combines both clinical and radiological variables. The former was used as a safety end point for intravenous thrombolysis with tissue plasminogen activator (IV-tPA)-related HT in the European Cooperative Acute Stroke Trials (ECASS) [3–5]. HI and PH are subdivided into type 1 and 2 for the milder and more severe forms, respectively (without HT, HI, PH, and PH2). PH2, the most severe form of HT, is classified as blood clots exceeding 30% of the infarct area with significant space-occupying effect. In cases of HT classed as ECASS-I, PH2 was associated with both neurological deterioration (OR 32.3) and increased 3-month mortality (OR 18) [4] compared with patients without PH2

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