Table 3

Studies correlating thrombus composition, clinical outcome and imaging characteristics

Ref. (year)	No of patients	r-tPA administered to eligible patients	Staining technique	Imaging technique	Main findings Revascularisation/clinical outcome imaging characteristics
Liebeskind et al 6 2011	50	Yes, IV r-tPA: 7 patients (14%), IA-r-tPA: 1 patient (2%)	H&E	HMCAS on NCCT and blooming artefact (BA) on GRE-MRI	RBC content determines appearance of HMCAS and BA and the absence of these signs may indicate fibrin-rich thrombi
Niesten et al 19 2014	22	Yes, IV r-tPA: 17 patients (77%) IA-r-tPA: 3 patients (14%)	H&E, Mallory’s phosphotungstic acid-haematoxylin (fibrin) IHC: glycophorin A (RBCs) and CD31 (platelets)	Thrombus attenuation on NCCT	Moderately positive correlation between RBC content and thrombus attenuation on NCCT
Boeckh-Behrens et al 9 2014	34	–	H&E, Elastica van Gieson staining	HAS on NCCT	Higher percentage of WBCs in the thrombus are associated with less favourable recanalisation(TICI<3) and clinical outcome (NIHSS score at discharge and mRS scores upto 90 days)
Kim et al 35 2015	37	Yes, IV r-tPA: 23 patients (62%)	H&E, IHC: glycoprotein IIIa(platelets), CD61	SVS on GRE-MRI	Higher RBC content correlates with positive SVS and negative SVS correlated with higher fibrin and platelet content
Ahn et al 15 2016	36	Yes, IV r-tPA: 20 patients (56%)	H&E, MSB IHC: CD42b (platelet glycoprotein Ib)	HAS on NCCT	No association between thrombus components and IV r-tPA use, HAS on NCCT No association between thrombus components and recanalisation grade
Berndt et al 57 2018	133		H&E	NCCT and CTA for clot perviousness	Pervious thrombi are fibrin/platelet rich
Maekawa et al 33 2018	43	Yes, IV r-tPA: 20 patients	H&E	Thrombus attenuation on NCCT	RBC rich thrombi are associated with higher thrombus density, and reduced procedure time
Shin et al 31 2018	37	Yes, IV r-tPA: 16 patients (43%)	H&E	HAS on NCCT/ blooming artefact on GRE-MRI	RBC-rich clots associated with successful recanalisation (TICI=2b/3) RBC-rich clots associated with presence of HAS/BA
Choi et al 39 2018	52	Yes, IV r-tPA: 52 patients (100%)	H&E, MSB	SVS on MRI	Higher % of RBCs associated with presence of SVS and better responsiveness to intravenous thrombolysis Thrombolysis responsiveness not directly associated with good clinical outcome (mRS score=0–2, after 3 months)
Fitzgerald et al 11 2019	85	Yes, IV r-tPA: 43 patients (51%)	MSB IFC: CD42b (platelets), fibrinogen	HAS on NCCT	Isodense clots on NCCT correlate with a high fibrin/platelet content
Fitzgerald et al 54 2019	50	Yes, IV r-tPA: 23 patients (46%)	H&E	HAS on NCCT	Positive correlation between RBC rich thrombi and presence of HAS
Horie et al 67 2019	65	Yes, IV r-tPA: 22 patients (34%)	H&E	MRI (SVS)	Stent retrievers might crush the thrombus, which may have a synergistic effect with r-tPA Thrombus histology might be altered during removal via thrombectomy No correlation between SVS and % of RBCs
Benson et al 58 2020	57	Yes, IV r-tPA: all patients (100%)	H&E, MSB	NCCT and CTA for clot perviousness	Pervious clots are RBC-rich whereas impervious clots are more likely to be fibrin and WBC rich

CTA, CT angiography; HAS, hyperdense arterial sign; HMCAS, hyperdense middle cerebral artery sign; IA, intra-arterial; IFC, immunofluorescence stainin; IHC, immunohistochemical staining; IV, intravenous; mRS, modified Rankin Scale; MSB, Martius scarlet blue; NCCT, non-contrast CT; NIHSS, National Institutes of Health Stroke Scale; RBC, red blood cell; r-tPA, recombinant tissue plasminogen activator; SVS, susceptibility vessel sign; TICI, Thrombolysis in Cerebral Infarction score; vWF, von Willebrand factor; WBC, white blood cell.