Electrical impedance spectroscopy signatures of red blood cells and platelets in acute ischemic stroke clots in the Clotbase International Registry: Significance for etiology and first pass effect

BACKGROUND: Clot composition plays a key role in the pathophysiology of Acute Ischemic Stroke (AIS) and impacts the effectiveness of treatments such as thrombolysis and mechanical thrombectomy (MT). Developing an electrochemical impedance spectroscopy (EIS) based device to identify clot characteristics could improve stroke treatment outcomes. This study aims to estimate the red blood cell (RBC) and platelet content in extracted AIS clots and explore EIS's relevance to clinically important parameters, including stroke etiology and First Pass Effect (FPE). METHODS: A total of 508 clots from 426 MT patients at five stroke centers in France, Japan, Serbia, and Spain (February 2021-2024) were analyzed in the Clotbase International Registry. EIS was performed on retrieved clots, followed by Martius Scarlet Blue staining and CD42b immunohistochemistry. EIS based models to quantify RBCs and platelets were designed using a development dataset (n=309), validated on a blinded dataset (n=199), and combined in a full dataset (n=508). Components (median interquartile range (IQR)) were quantified, correlating RBC and platelet percentages with impedance and clinical parameters. RESULTS: Correlations between content as determined by EIS and histology were validated in a blind dataset for RBCs (r=0.7, P<0.0001) and platelets (r=0.5, P<0.0001). Similar correlations were observed in the full dataset. Large-artery atherosclerosis clots had significantly higher RBC (46.0% (25.7-67.7)) and lower platelet content (31.7% (22.4-42.7)) compared with cardioembolic (RBCs: 34.9% (14.0-56.2); platelets: 36.5% (26.7-51.0)) and cryptogenic (RBCs: 31.5% (17.4-63.6); platelets: 37.8% (28.4-50.8)). FPE was associated with significantly higher RBC (40.0% (25.6-55.4) vs non-FPE: 31.2% (6.6-50.2)) and lower platelet content (42.0% (32.0-54.0) vs non-FPE: 47.7% (30.6-65.0)), confirmed by histology. CONCLUSION: EIS of RBCs and platelets provide an accurate assessment of clot composition, correlating strongly with histology. EIS holds the potential to deliver clinically relevant information on clot characteristics at the point of care.