Haemorrhagic transformation of ischaemic stroke : risk factors and prognostic implications

Abstract

Background: Ischaemic stroke is a devastating disease with potentially severe complications. In particular, haemorrhagic transformation (HT) of ischaemic strokes is a complication that has been associated with significant morbidity and mortality. HT can be divided into four subtypes based on their radiological appearance into haemorrhagic infarction types 1 (HI1) and 2 (HI2) and parenchymal haematoma types 1 (PH1) and 2 (PH2) or based on whether the HT coincides with neurologic deterioration into symptomatic (SHT) or asymptomatic HT (AHT). Previous studies found PH2 to be the only subtype to worsen clinical outcomes, however, the effects of the different forms of HT have not been explored in Chinese patients in Hong Kong, where only a minority of patients receive thrombolysis. Thus, the objective of this study was to identify the risk factors for HT and to determine the effects of the different forms of HT on mortality, functional outcome and the risk of developing recurrent ischaemic stroke and dementia. Methods: This study was a retrospective cohort study of consecutive patients with acute ischaemic stroke who were admitted to Queen Mary Hospital between 1 January 2007 and 31 December 2011. A diagnosis of HT was made by examination of a follow-up computed tomography or magnetic resonance imaging scan performed 2.5±2.6 days after a baseline CT scan obtained on the day of stroke onset. The outcomes of the study were mortality at 90 days and 5 years, the development of poor outcome (modified Rankin scale >2 and/or mortality at 90 days), ischaemic stroke recurrence and development of dementia. Demographic information, clinical data including information related to co-morbidities, medications and laboratory variables were collected. Results: Among a total of 718 patients included in the final analysis, 117 (16.3%) had HT. PH was more common than HI. HI occurred in 15 (12.8%) of patients, among the HI cases, 12 patients developed HI1 and 3 had HI2. PH occurred in 102 patients (87.2%), within PH, PH1 occurred in 46 patients, PH2 occurred in 54 and PH at a remote site was observed in 2 patients. At 90 days, 138 patients had died (19%) and 462 (64%) had a poor outcome. The development of HT was independently predicted by rt-PA administration (adjusted OR 2.86, 95% CI 1.58-5.18, p=0.001), a diagnosis of cardioembolic stroke (adjusted OR 3.65, 95% CI 2.23-5.97, p<0.001) and use of warfarin on admission (adjusted OR 2.85, 95% CI 1.27-6.39, p=0.011). The hazards of 90 day mortality were significantly increased by PH2 (adjusted HR 1.86, 95% CI 1.07-3.24, p=0.028) and SHT (adjusted HR 1.87, 95% CI 1.10-3.20, p=0.022). Likewise, the hazards of 5 year mortality were also increased in patients with PH2 (adjusted HR 1.53, 95% CI 1.01-2.30, p=0.044) and SHT (adjusted HR 1.53, 95% CI 1.02-2.28, p=0.038). Predictors of poor outcome on multivariate logistic regression were any form of PH (adjusted OR 1.87, 95% CI 1.10-3.19, p=0.021), PH2 (adjusted OR 2.14, 95% CI 1.04- 4.40, p=0.039) and SHT (adjusted OR 2.57, 95% CI 1.11-5.97, p=0.028). HT did not significantly increase the hazards of recurrent ischaemic stroke in survivors of the index stroke or dementia in previously dementia-free survivors. Conclusion: HT was independently predicted by rt-PA use, cardioembolic stroke and use of warfarin on admission, which emphasizes the importance of appropriate patient selection for treatment with rt-PA. PH2 and SHT have significant impacts on mortality and functional outcome while HI, PH1 and AHT had no effects on prognoses, therefore, HT should be viewed as a multifaceted phenomenon that may affect the prognosis of stroke patients to varying degrees depending on the subtype.