Ischemic Stroke: Histological Thrombus Composition and Pre-Interventional CT Attenuation Are Associated with Intervention Time and Rate of Secondary Embolism

Abstract

Background and Purpose: The introduction of stent retrievers has made the complete extraction and histological analysis of human thrombi possible. A number of large randomized trials have proven the efficacy of thrombectomy for ischemic stroke; however, thrombus composition could have an impact on the efficacy and risk of the intervention. We therefore investigated the impact of histologic thrombus features on interventional outcome and procedure-related embolisms. For a pre-interventional estimation of histologic features and outcome parameters, we assessed the pre-interventional CT attenuation of the thrombi. Methods: We prospectively included all consecutive patients with occlusion of the middle cerebral artery who underwent thrombectomy between December 2013 and February 2016 at our university medical center. Samples were histologically analyzed (H&E, Elastica van Gieson, Prussian blue); additionally, immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. Main thrombus components (fibrin, erythrocytes, and white blood cells) were determined and compared to intervention time, frequency of secondary embolisms, as well as additional clinical and interventional parameters. Additionally, we assessed the pre-interventional CT attenuation of the thrombi in relation to the unaffected side (rHU) and their association with histologic features. Results: One hundred eighty patients were included; of these, in 168 patients (93.4%), complete recanalization was achieved and 27 patients (15%) showed secondary embolism in the control angiogram. We observed a significant association of high amounts of fibrin (p < 0.001), low percentage of red blood cells (p < 0.001), and lower rHU (p < 0.001) with secondary embolism. Higher rHU values were significantly associated with higher amounts of fibrin (p ≤ 0.001) and low percentage of red blood cells (p ≤ 0.001). Additionally, high amounts of fibrin were associated with longer intervention times (p ≤ 0.001), whereas thrombi with high amounts of erythrocytes correlated with shorter intervention times (p ≤ 0.001). ROC analysis revealed reliable prediction of secondary embolisms for low rHU (AUC = 0.746; p ≤ 0.0001), low amounts of RBC (AUC = 0.764; p ≤ 0.0001), and high amounts of fibrin (AUC = 0.773; p ≤ 0.0001). Conclusions: Fibrin-rich thrombi with low erythrocyte percentage are significantly associated with longer intervention times. Embolisms in the thrombectomy process occur more often in thrombi with a small fraction of red blood cells and a low CT-density, suggesting a higher fragility of these thrombi.

Why we fail: mechanisms and co-factors of unsuccessful thrombectomy in acute ischemic stroke

“…Recent literature also shows inconclusive findings concerning this aspect [24]. There are studies and histological analysis that come to a similar result [25,26], while other investigations indicate the opposite: cardiogenic thrombi seem to have a higher proportion of fibrin compared to other stroke etiologies, associated with worse interventional recanalization rates [27][28][29]. More studies on thrombus etiology and thrombus composition must be performed.…”

Influence of Thrombus Composition on Thrombectomy: ADAPT vs. Balloon Guide Catheter and Stent Retriever in a Flow Model

“…For the moment the clot attenuation on non-enhanced CT (NECT) is promising. There is a link between the density of the clot and the histological composition [24,25]. Since almost every patient undergoes NECT, the workflow would not be significantly affected and no delay of therapy would occur.…”

Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?

“…These findings have implications for clot retrieval: increased clot density on NCCT and high RBC density on histologic analysis have been shown to be associated with successful recanalization after thrombectomy and reduced thrombectomy procedure time 16–18. Conversely, Sporns et al found that fibrin-rich clots are associated with increased intervention time, and are more susceptible to embolism during thrombectomy, possibly reflecting fragility of clots with high fibrin levels 19…”