Qing Hao, MD

Sporns PB, Hanning U, Schwindt W, Velasco A, Minnerup J, Zoubi T, et al. Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus? Stroke. 2017

During the hyperacute phase of stroke, we all get excited when the interventionists show a piece of clot attached to the device, and then we primarily focus on the cause of the clot by performing various workups, although many times the answer is “unknown.” Can we get some clues from the clot itself?

Sporns and colleagues analyzed the histological clot composition with the aim to define characteristics that would further help to determine the cause of stroke. Clots were collected from 187 acute stroke patients with carotid-T or middle cerebral artery occlusion who underwent thrombectomy at a university medical center. In addition to quantification of fibrin, RBC, and WBC, immunohistochemistry for CD3, CD20, and CD68/KiM1P was also performed.

Based on the clinical characteristics and workup results, cardioembolic stroke (TOAST2) was found in 77 patients, large artery atherosclerosis (TOAST1) in 35, other determined etiology (TOAST4, cryptogenic) in 11, and undermined etiology in 64. TOAST 1 and 4 were combined as non-cardioembolic stroke in this analysis.

Compared with non-cardioembolic stroke, the cardioembolic and cryptogenic stroke patients had a statistically significant higher proportion in fibrin and WBCs, lower proportion in RBCs (fibrin: 60% and 63% vs. 51.5%; WBC  8% and 10% vs. 5%; RBC: 28% and 26% vs. 42%;). The immunohistochemical analysis, including CD3, CD20, were similar across the three groups, although a trend of higher CD68/KiM1P was observed in cardioembolic compared with non-cardioembolic strokes.

Several considerations should be kept in mind when interpreting the analyses and planning for future studies:

  1. The similarity of the clot composition between the cardioembolic and cryptogenic stroke supported the hypothesis that most cryptogenic strokes are probably cardioembolic. However, further studies are needed to explore the accuracy (e.g. sensitivity, specificity, positive predictive values, and negative predictive value) of clot features in defining stroke mechanism, particularly, can we attribute cryptogenic stroke to cardioembolic sources based on the histological features of the clot?
  2. The immunohistochemical analysis showed similar results across the three groups; however, only three markers were tested. Which parameters would be more sensitive and specific to different types of clot sources? What is the potential pathophysiological mechanism for the trend (relative small sample size may decrease the power) of higher CD68/KiM1P in cardioembolic stroke?
  3. In addition to iv-tpa use, several other factors may affect the clot position, as the author mentioned: Part of the thrombus, rather than the whole piece, being obtained during the interventional procedure may cause bias; manipulation of the clot may affect the clot composition. In addition, the components of clots may change over the time, while each patient’s recanalization time is different.

We look forward to more research to clarify the role of histopathological analysis of clot in determining stroke etiology, and maybe one step further, guiding the second stroke prevention strategies.