Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment

Abstract

Background and Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0–3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2–3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0–1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0–2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72–20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21–5.51]). Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial

“…12,16,17 The effect of early reperfusion on good outcome was maintained even after adjustment for the final eTICI score, suggesting that its benefit mainly lies in the shorter ischemia duration of the reperfused tissue, better collateral blood flow from recanalized vessels, or less hemorrhagic complications, rather than solely in improvement of postprocedural eTICI scores. [16][17][18] In fact, our results showed that, despite higher rates of ≥2a reperfusion and nominally higher final eTICI ≥2b rates on the last angiographic run, complete reperfusion (final eTICI 3) rates were lower in patients with early reperfusion. This is in line with a previous study by Alves et al, 17 who suggested that the occurrence of early reperfusion or thrombus migration may render it more challenging for the neurointerventionalist to achieve complete reperfusion, since early reperfusion could convert an M1 segment occlusion, which is relatively easy to access, into several more distal occlusions, which are much more difficult to treat by endovascular means.…”

Acute Reperfusion Therapies for Acute Ischemic Stroke

“…Further, there is an increased risk of clot migration, distal migration that hampers MT recanalization scores, and an increased risk of ICH. On the other hand, IV alteplase has shown effectiveness in distal MCA occlusion as well as facilitation of MT with thrombolysis of clot fragments during stent retrieval [55]. Recent randomized trials have improved our understanding of the optimal treatment algorithm.…”

Direct mechanical thrombectomy without intravenous thrombolysis versus bridging therapy for acute ischemic stroke: A meta-analysis of randomized controlled trials

“…23 There is an ongoing debate on the use of IVT before MT, proponents of which feel may favorably alter clot properties to facilitate removal, lyse distal thrombi, and theoretically lead to higher first-pass effect rates and successful reperfusion. 24 However, it may also lead to clot fragmentation and render a patient ineligible for MT due to distal migration. On the other hand, dMT may allow faster door-to-groin-puncture times.…”