Tapan Mehta, MBBS, MPH

Choi MH, Park GH, Lee JS, Lee SE, Lee S-J, Kim J-H, et al. Erythrocyte Fraction Within Retrieved Thrombi Contributes to Thrombolytic Response in Acute Ischemic Stroke. Stroke. 2018

Clots retrieved from mechanical thrombectomy have been analyzed/studied in the past decade by multiple investigators, and the interest is growing with improved clot retrieval devices. Choi et al. investigate response of intravenous thrombolytics on mechanically retrieved clots in a single-center retrospective study that was conducted over 2 years.

Patients with large vessel anterior circulation strokes receiving tPA within 4.5 hours with baseline mRS <= 2, NIHSS >=4, and ASPECT>=6 were included in the study. Patients also receive baseline MRI before the procedure specifically to evaluate clot burden and nature using the Gradient Echo sequence. The response to intravenous thrombolytic was determined using the Clot Burden Score comparing baseline CTA to conventional angiogram pre thrombectomy images. Additional assessment of intravenous thrombolytic effectiveness was also assessed using the Qureshi scale. Mechanical thrombectomies were performed using Solitaire and Trevo stent retriever device or Penumbra suction catheter. The thrombectomy approaches were not universal; the authors mention use of angioplasty and tirofiban infusion in cases with initial failed attempts. The clots (including all pieces) retrieved from thrombectomy were fixed in 10% neutral buffered formalin. Subsequently, paraffin wax embedded tissues were cut into 4-micro meter sections and stained with hematoxylin-eosin and Martius scarlet blue staining. The sections were digitally scanned and analyzed by blinded examiners. Subgroups based on RBC content with the lowest, middle and highest tertiles and Intravenous thrombolytic responsiveness were further examined.

Study flowchart.

Figure 1: Study flowchart.

Figure 1 describes the numbers for included and excluded cases for further analysis. Hypo intensity on gradient echo sequences did correlate with RBC content. Interestingly, the RBC fraction was higher in the intravenous thrombolytic responsive group (45.7±15.5% versus 35.9±12.2%; P=0.010), whereas fibrin and platelet fractions were higher in the IVT-unresponsive group (50.4±14.0% versus 58.5±11.1%; P=0.027). The IVT unresponsive group revealed higher WBC fraction compared with the IVT-responsive group (3.9±2.1% versus 5.5±3.0%; P=0.027). In the univariate analysis, RBC and WBC fraction had significant effects on intravenous thrombolytic response (RBC fraction: odds ratio, 1.06; 95% confidence interval, 1.01–1.11; WBC fraction: odds ratio, 0.78; 95% confidence interval, 0.62–0.99). After adjusting for age, hypertension, baseline NIHSS, baseline CBS, and WBC fraction, the RBC fraction remained the only positive factor for the response to IVT (odds ratio, 1.05; 95% confidence interval, 1.01–1.10).

As the authors have mentioned, these findings have to be interpreted with caution. The clots with complete recanalization (16.3%) and those which disappeared during retrieval process (17.3%) are not included in this analysis, which can significantly bias the results. Considering the practical aspects of large vessel stroke treatment, in a retrospective study, it is reasonable to compare the CT angiogram with pre-thrombectomy injection of conventional angiogram for estimation of recanalization attributed to intravenous thrombolytics. However, position of catheter tip and force of injection during conventional angiogram, and timing of CT angiography contrast bolus could also create a potential bias in measurements.

Choi et al present an interesting concept of assessing the effectiveness of intravenous thrombolytics based on clot composition in real-time clinical settings. Moving forward, to create larger databases establishing these correlations, it is important to standardize the clot analysis methods which are feasible for most of the centers performing mechanical thrombectomies.