The complication is more frequent than currently recognized, with a significant portion occurring after the first 24 hours.
Two recent studies shed light on the development of hemorrhagic transformation following mechanical thrombectomy for large vessel occlusion (LVO) stroke and how it impacts outcomes.
Despite some contradictions between the reports, it seems clear that certain types of hemorrhagic transformation increase the risk of poorer outcomes and are more common than currently recognized. Questions remain as to how to prevent the complication, but one of the studies suggests that rapid and successful recanalization may reduce risk.
Both studies were published online recently in the Journal of NeuroInterventional Surgery.
Looking for Predictors
In the first, Yu Bin Lee (Chonnam National University Medical School, Gwangju, South Korea), and colleagues retrospectively reviewed data from 400 patients with acute LVO stroke who underwent thrombectomy to identify independent predictors of hemorrhagic infarction and parenchymal hematoma on posttreatment CT scans. They also looked at the association between hemorrhagic transformation and poor outcome, defined as a 90-day mRS ≥ 3.
Overall, 98 patients experienced hemorrhagic transformation, including 62 (15.5%) with hemorrhagic infarction and 36 (9%) with parenchymal hematoma. Only parenchymal hematoma was an independent predictor of poor outcome, with an odds ratio (OR) of 10.15 (95% CI 3.26-31.63).
Independent predictors of hemorrhagic infarction were male sex, atrial fibrillation, and time from symptom onset to groin puncture. Hyperlipidemia (OR 0.22; 95% CI 0.06-0.77) and successful reperfusion (OR 0.25; 95% CI 0.09-0.65) were independently associated with a lower chance of parenchymal hematoma, while hypertension (OR 2.26; 95% CI 1.01-5.04) and longer procedure duration (OR 1.05; 95% CI 1.02-1.08) were independently associated with a higher chance of parenchymal hematoma.
Taking Follow-up Infarct Volume Into Account
In the second study, Katinka R. van Kranendonk (Academic Medical Center, Amsterdam, the Netherlands) and colleagues used the MR CLEAN dataset to assess the association between radiological subtypes of hemorrhagic transformation and functional outcome. Hemorrhagic transformation was classified on follow-up CT scans according to the European Cooperative Acute Stroke Study II classification.
“Follow-up infarct volume is an important predictor of functional outcome, and large infarct volumes are associated with hemorrhagic transformation,” van Kranendonk told Neurovascular Exchange in an email. “Not all studies include follow-up infarct volume in the analysis, and therefore an association of hemorrhagic transformation with functional outcome might be driven by a large underlying infarct. It is complicated to separate the impact of infarct volume and hemorrhagic transformation on functional outcome. However, we decided that it is necessary to adjust for follow-up infarct volume to make conclusions about the impact of hemorrhagic transformation on functional outcome.”
Among the 478 patients in the trial with available follow-up imaging, 222 had hemorrhagic transformation. Of these, 76 (16%) were classified as hemorrhagic infarction type 1; 71 (15%) as hemorrhagic infarction type 2; 36 (8%) as parenchymal hematoma type 1; and 39 (8%) as parenchymal hematoma type 2.
Only two types of hemorrhagic transformation were significantly associated with worse functional outcome: hemorrhagic infarction type 2 (P = 0.001) and parenchymal hematoma type 2 (P = 0.009). There was also a trend toward an increased risk of worse outcome with hemorrhagic transformation type 1 (P = 0.058).
“That both hemorrhagic infarction type 1 and type 2 were associated with a poor functional outcome is not often reported,” noted van Kranendonk. However, “as some patients with hemorrhagic transformation type 1 show acute neurological deterioration, it is possible that it could be of influence on long-term functional outcome.”
She was surprised to find that parenchymal hematoma type 1 was not associated with poor functional outcome, as was expected and as was seen in the Lee at al study. She suspects this may be due to the small number of patients who developed it in the trial.
“The finding that in our study both hemorrhagic infarction types 1 and 2 were associated with a poor functional outcome contradicts somewhat with the results of Lee et al, in which hemorrhagic infarction was not associated with a poor functional outcome,” pointed out van Kranendonk.
She believes this contradiction can be explained by some notable differences in the two studies. In particular, there was a higher overall incidence of hemorrhagic transformation in the MR CLEAN database than in the Lee at al database. This may be largely explained by the fact that “most of our patients were classified with hemorrhagic transformation on 5-day follow-up imaging, while the Lee et al study assessed hemorrhagic transformation on 24-hour follow-up imaging,” she explained. This means the complication may often occur more than 24 hours after the procedure.
“Hemorrhagic transformation is much more common than initially thought, and it is of importance regarding functional outcome,” concluded van Kranendonk. “Additionally, in the acute phase, hemorrhagic transformation can seem asymptomatic, although it does have a negative impact on functional outcome at 3 months.”
Many unanswered questions remain, noted van Kranendonk.
“How do we prevent hemorrhagic transformation? Would omitting IV alteplase decrease the risk of hemorrhagic transformation and improve stroke treatment? This question might be answered soon by the results of trials comparing direct thrombectomy with usual care and treatment with IV alteplase before thrombectomy, such as MR CLEAN NO-IV, SWIFT DIRECT, DIRECT-SAFE, and DIRECT MT,” she predicted.
Sources:
- Lee YB, Yoon W, Lee YY, et al. Predictors and impact of hemorrhagic transformations after endovascular thrombectomy in patients with acute large vessel occlusions. J NeuroIntervent Surg. 2018;Epub ahead of print.
- Van Kranendonk KR, Treurniet KM, Boers AMM, et al. Hemorrhagic transformation is associated with poor functional outcome in patients with acute ischemic stroke due to a large vessel occlusion. J NeuroIntervent Surg. 2018;Epub ahead of print.
Disclosures:
- Lee and Van Kranendonk report no relevant conflicts of interest.
