In this study, we analyzed and compared the whole blood clots and plasma clots from components, TEG analysis, MRI, histological examination and tension test. The result elucidated that whole blood contained rich RBCs has significantly higher MA and retrieval strength compared with plasma thrombus which is lack of RBCs, which was positively correlated with retrieval strength. Moreover, RBC-rich clots showed less homogenous compared with RBC-deficiency clots. The results were comparable whether the clots originated from arterial or venous blood.
Thrombi histopathologic characteristics in ischemic stroke could provide insights into stroke etiology and ideal treatment strategies [15–17]. The origin of thrombus from different subtypes of stoke, as defined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, were still controversial. Previously, Kim et. al  analyzed retrieved clots from 22 acute ischemic stroke patients, and elucidated that cardioembolic clots had a significantly higher proportion of RBCs and a lower proportion of fibrin compared with those originated from large-artery atherosclerosis. However, recent studies [19, 20] showed that lower content of RBCs and higher content of fibrin/platelets was associated with cardioembolic origin. This discrimination may rise from the bias of inclusion criteria such as racial and individual properties, the use of alteplase or urokinase, mechanical treatment strategies as well as thrombus features including clot burden, location or generated time. Accordingly, autologous thrombus used in this study to semi-quantitively analyze their properties may be a good choice to find potential evidence.
Recent studies have thrown more light on the relationship between thrombus histopathology and mechanical thrombectomy. Among the properties of thrombus, the fibrin and red blood cell proportion in a thrombus determines its physical properties and how it responds to thrombectomy . High RBC proportion of RBCs has been proved to be associated with successful reperfusion [21, 22]. Gunning et.al also demonstrated that fibrin-rich thrombi comprising < 20% RBCs would decrease revascularization rates regardless of the technique employed. In our study, we found high proportion of RBCs in a thrombus increased the retrieval strength, however, tended to be more fragile during stent retrieval. One potential reason is the heterogeneity of the RBC-rich thrombus (as shown in Fig. 2) increased the surface adhesive friction, which has been considered as a predominant factor interacting with stent . Another reason may underlie that mature clot rich in fibrin is firmer and less deformable when interacting with stent retriever . However, the fibrin-rich clots used in our study were fresh made, which made them soft enough to be trapped and extracted. These potential reasons need further evidences proved by ultrastructural tests, such as electron microscopy.
Except for diverse clinical manifestations, image findings give us more direct diagnostic information of cerebral ischemic events. The presence of hyperdense artery sign (HAS) on CT and susceptibility vessel sign (SVS) on MRI are early signs of brain ischemic stroke, which have been recognized as higher RBC fraction within retrieved thrombus [10, 18, 21] and better clinical outcomes [21, 24]. Compare with HAS, SVS is reported to be higher sensitivity (about 70% VS. 30%) [10, 24]. In the present study, we used GRE T2*MR imaging sequence to identify SVS and found consistent results with previous studies. Moreover, we also found an interesting phenomenon that RBC-rich clots transformed to be more irregular during thrombogenesis under quiet circumstance in vitro. Under the ‘water-hammer’ effect in vivo, whether the flexibility of RBC-rich thrombus affected the ultimate shape of a clot or the interaction with a stent still needs more investigation.
High MA were tended to be female gender, lower hemoglobin levels, high platelet counts and fibrinogen, inflammation, and were more likely to have intracranial artery stenosis and large-vessel subtype strokes . We also found a moderate association of high TEG-MA with increased clot retrieving strength. High retrieval strength reflects the increased friction between the vessel wall and a clot trapped in a stent. When the fiction exceeds the ductility of a clot or the interaction strength between a thrombus and the stent, the clot would be dropped or fragmented. Therefore, a high radio force stent would be theoretically more suitable for stroke patients with high MA. Moreover, arterial and venous MA exhibited no significant difference, which was in accordance with previous in vitro study .
This study has some limitations. Firstly, this is an in vitro designed study, aiming to minimize the possible bias. However, the content of blood cells was semi-quantified, and the in vivo repeatability needs further proofs. Secondly, despite of the fact that mechanical thrombectomy with stent was till the mainstream method for ischemic stroke. Other effective strategies, such as thrombolysis or catheter aspiration, were not evaluated in the present study. Last but not least, although the results from this study demonstrated significant differences in thrombus properties, our study was not designed to deeply evaluate the possible mechanisms for these differences. None the less, based on the novel findings in the present study, we appreciate the fact that stroke patients with SVS on MRI (indicating a high RBC fraction clot) or with high MA tested by TEG, may need a higher radio force stent during mechanical thrombectomy. This suggestion might be difficult to accept by clinicians, a bold new approach is needed to address this novel calling.