Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Abstract

We aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.

Keywords: Acute stroke; Flow cytometry; Granulocytes; Mechanical thrombectomy; Recanalization; Thrombi.

Fig. 1

Flow chart. EVT is endovascular treatment; FC is flow cytometry; MT is mechanical thrombectomy; Mtici is modified thrombolysis in cerebral infarction; PIS is permanent intracranial stenting

Fig. 2

Differences in clot analysis among EVT with multiple passes. MT failure was associated with higher proportion of granulocytes [82.46% (69.19–89.02) vs. 69.90% (59.0–76.84); p < 0.001] and lower proportion of monocytes [17.11% (12.18–27.10) vs. 9.18 (5.29–20.23); p < 0.001] in clot analysis

Fig. 3

Correlation between clot stiffness and clot composition by flow cytometry