Melanie R. F. Greenway, MD
With cryptogenic stroke comprising 20-30% of all ischemic stroke, many researchers are investigating a variety of methods to de-mystify cryptogenic stroke. In this article, potential biomarkers of the clot retrieved from mechanical thrombectomy were compared to the known stroke cause to evaluate potential clot characteristics that may predict stroke cause.
Glycoprotein VI (GPVI), heme, and DNA content were used to evaluate platelet, red blood cell, and leukocyte content of a random sample of 250 thrombi from 1209 consecutive acute ischemic stroke patients who underwent mechanical thrombectomy.
The thrombus specimens were grinded through a tissue lyser, and thrombus homogenates were recovered after centrifugation. RBC content was estimated using heme concentration. GPVI levels were used to estimate platelet concentration. DNA content was quantified as an estimation of leukocyte count.
Stroke cause was classified based on standard workup, including MRI, CT, MRA, EKG recording of 1-3 days duration, transthoracic and/or transesophageal echocardiogram. Causes were defined as cardioembolic (124, 56.8%), noncardioembolic (33, 13.2%), and undetermined (75, 30%).
The main finding of the study was that cardioembolic stroke had a higher DNA content and higher DNA/GPVI ratio compared with noncardioembolic, which is to say the thrombi of cardioembolic stroke had a higher concentration of leukocytes and lower concentration of platelets. The heme content was not different between the two groups. Applying this information to the ESUS patients, sensitivity and specificity was calculated, and they found that about 50% of thrombi in ESUS patients could be calculated as cardioembolic with a specificity of 90%.
Embolic stroke of undetermined source (ESUS) represents cryptogenic stroke that appears embolic based on certain radiographic criteria, and has become a target of research. Recent double-blind randomized control trials such as RE-SPECT-ESUS and NAVIGATE-ESUS reported no difference in recurrent stroke when using anticoagulation versus antiplatelet therapy, suggesting a need for further refinement of the stroke mechanism in individual patients to guide secondary stroke prevention.
This study further describes histopathological heterogeneity of thrombi after mechanical thrombectomy and provides possible biomarkers for cardioembolic stroke. A prior study showed cardioembolic thrombi to have higher leukocyte components based on a semiautomated color-based segmentation similar to the current study, but reported higher to proportion of fibrin/platelets compared to noncardioembolic stroke. One reason for this discordance is likely the difference in technique, as the earlier study was unable to distinguish between fibrin and platelets.1 Other studies have used histopathologic characteristics as well as radiographic characteristics of clot to predict recanalization rates.2-4
Utilization of histopathologic characteristics of thrombus after mechanical thrombectomy provides interesting opportunities for further research that could personalize secondary stroke prevention, potentially guiding both diagnostic and therapeutic strategies in the acute hospital setting.
References:
1. Boeckh-Behrens, et. al. Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke. 2016;47:1864–1871
2. De Meyer, et al. Analyses of thrombi in acute ischemic stroke: a consensus statement on current knowledge and future directions. Int J Stroke. 2017;12:606–614.
3. Hashimoto, et. al. Histopathologic Analysis of Retrieved Thrombi Associated With Successful Reperfusion After Acute Stroke Thrombectomy. Stroke. 2016;47:3035–3037
4. Hofmeister J, Bernava G, Rosi A, Vargas MI, Carrera E, Montet X, Burgermeister S, Poletti P-A, Platon A, Lovblad K-O, Machi P. Clot-Based Radiomics Predict a Mechanical Thrombectomy Strategy for Successful Recanalization in Acute Ischemic Stroke. Stroke. 2020;51:2488–2494.
