Frequency and risk factors for spontaneous hemorrhagic transformation of cerebral infarction

Hemorrhagic transformation of cerebral infarction (HTI) occurs spontaneously but its frequency and risk factors are uncertain with mixed results in previous studies. We aimed to determine the overall frequency of and risk factors for HTI.

We performed a systematic review according to Cochrane Collaboration methods of published reports of HTI with reliable, systematic follow-up with computed tomography or magnetic resonance imaging.

In all, 28 observational studies and 19 randomized controlled trials in stroke were identified that included follow-up imaging data. Problems with inconsistent definitions or small and biased patient populations limited detailed interpretation. The overall frequency of any HTI in untreated patients was 8.5% (95% confidence interval 7%-10%). Severe HTI (i.e., HTI accompanied by neurologic deterioration or parenchymal hematoma formation) occurred in 1.5% (95% confidence interval 0.8%-2.2%). The frequency of HTI increased markedly with increasing use of antithrombotic or thrombolytic drugs. Magnetic resonance imaging detected more HTI than did computed tomography. The published data were generally inadequate to undertake more detailed analysis of risk factors. However, in the 8 studies that did provide the information, HTI was associated with large infarcts, mass effect, hypodensity observed early after the stroke, and age older than 70 years, but not hypertension or cardioembolic stroke.

Severe HTI is uncommon in patients not receiving antithrombotic or thrombolytic agents. The methods used to assess the frequency of and risk factors for HTI, particularly a standard of definitions in future prospective studies, could be improved.