Thrombolysis in Stroke Patients with ASPECTS <5
Patients with acute ischemic stroke and ASPECTS score less than 5 should generally NOT receive IV thrombolysis due to substantially increased risk of hemorrhagic transformation and poor functional outcomes, though endovascular thrombectomy may still be considered in carefully selected cases within 6 hours.
Evidence-Based Rationale
Standard Thrombolysis Guidelines and ASPECTS Thresholds
The major clinical practice guidelines do not explicitly address ASPECTS <5 as an absolute contraindication, but the evidence strongly suggests caution:
IV r-tPA is recommended within 3 hours of symptom onset (Grade 1A) and suggested within 3-4.5 hours (Grade 2C) for eligible patients, but these recommendations assume patients meet standard imaging criteria 1.
The 2015 AHA/ASA guidelines for endovascular treatment specify ASPECTS ≥6 as an inclusion criterion for stent retriever therapy within 6 hours, implicitly suggesting that ASPECTS <6 represents substantial early ischemic change that increases risk 1.
Research Evidence on Low ASPECTS Scores
The research literature provides compelling evidence against thrombolysis in patients with ASPECTS <5:
In a prospective study of 49 patients receiving tPA within 3 hours, those with DWI ASPECTS ≤5 had significantly worse outcomes: only 1 of 8 patients (12.5%) showed dramatic improvement compared to 21 of 41 patients (51%) with ASPECTS >5 2.
Bad outcomes occurred in 75% (6 of 8) of patients with ASPECTS ≤5 versus only 5% (2 of 41) with ASPECTS >5 (P<0.0001) 2.
Multivariate analysis identified ASPECTS ≤5 as the only independent predictor of bad outcome (OR 33.4,95% CI 2.7-410.8), indicating that extensive early ischemic changes predict poor response to thrombolysis 2.
In the ECASS II trial analysis, patients with ASPECTS ≤7 had substantially increased risk of thrombolytic-related parenchymal hemorrhage, with a significant treatment-by-ASPECTS interaction (P=0.043) 3.
Clinical Decision Algorithm
For patients presenting within 4.5 hours with ASPECTS <5:
Do NOT administer IV thrombolysis due to high risk of hemorrhagic transformation and poor functional outcomes 2, 3.
Consider endovascular thrombectomy with stent retrievers if the patient meets other criteria (ICA or M1 occlusion, prestroke mRS 0-1, NIHSS ≥6, age ≥18, groin puncture possible within 6 hours), though benefits are uncertain with ASPECTS <6 (Class IIb evidence) 1.
Initiate aspirin 160-325 mg within 48 hours as standard acute stroke care (Grade 1A) 1, 4.
Provide VTE prophylaxis with prophylactic-dose LMWH for patients with restricted mobility (Grade 2B) 1, 4.
Important Caveats and Pitfalls
Common pitfalls to avoid:
Do not rely solely on non-contrast CT appearance if advanced imaging (DWI-MRI) is available, as DWI is more sensitive for detecting early ischemic changes and calculating ASPECTS 2.
Do not assume all patients with low ASPECTS are ineligible for any reperfusion therapy - endovascular thrombectomy may still be considered in highly selected cases, particularly with proximal large vessel occlusion 1.
Recognize that ASPECTS <5 represents approximately one-third or more of the MCA territory already infarcted, which fundamentally limits the potential salvageable penumbra and increases hemorrhagic risk 2, 3.
Special considerations:
Recent guidelines for endovascular treatment (2015 AHA/ASA) used ASPECTS ≥6 as an inclusion criterion in major trials (MR CLEAN, REVASCAT), suggesting that ASPECTS <6 falls outside the evidence base for proven benefit 1.
The Canadian guideline recommends using ASPECTS with a cut-off score of 6 for thrombectomy eligibility within the first 6 hours, further supporting that scores below this threshold represent excessive early ischemic burden 1.
Age, baseline NIHSS, and time to treatment do not modify the poor prognosis associated with ASPECTS ≤5, making this an imaging-based contraindication that supersedes other favorable clinical factors 2.