Ellis van Etten, MD, PhD
Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Original article: High thrombus platelet content is associated with a lower rate of first pass effect in stroke treated by endovascular therapy. European Stroke Journal. DOI: 10.1177/23969873221108740
A tough clot: platelet-rich thrombi and efficacy of endovascular therapy
In acute ischemic stroke with large vessel occlusion, the efficacy of endovascular treatment (EVT) depends strongly on the ability to obtain successful recanalization. Complete recanalization after a single EVT pass – known as the first pass effect (FPE) – is associated with the best clinical outcome. Using quantitative assays, the study from Delvoye and his colleagues evaluates the potential link between clot cellular composition and outcome after EVT.
This study collected thrombi from stroke patients and had the recanalization status scored by experienced neuro-interventionalists. Thrombi that weight over 10 mg were lysed with a special homogenization method. Then quantification of red blood cells and white blood cells in the thrombus homogenates was performed by measuring the heme concentration, and DNA content respectively. Platelet content was estimated by measuring GPVI levels in the thrombus homogenates.
The study team retrieved a total of 729 thrombi of which 250 were large enough to be homogenized. Of those 250 thrombi, the median number of passes during EVT was 2 (range 1 – 12) and FPE was achieved in 36%.
Thrombus GPVI levels were significantly different between patients with and without FPE; the mean GPVI content being significantly lower in the first pass effect group. After adjusting for potential confounding factors, including use of IV tPA therapy and occlusion site, a lower CPVI concentration remained significantly associated with first pass effect (OR 0.55 (95% CI 0.39 0 0.79; p <0.001). Higher GPVI levels were also associated with an increased number of passes, a longer reperfusion time, and a lower reperfusion rate. No difference was found in heme and DNA content.
Therefore, they authors conclude that platelet concentration seems to be affecting first pass effect occurrence, as opposed to red blood cell content and white blood cell content. This study strengthens the existing evidence of the association between platelet-rich thrombi and a lower recanalization rate. From a pathophysiologic perspective, this might occur because of increased thrombus stiffness and friction caused by platelets colocalizing with fibrin, neutrophils, neutrophil extracellular traps, and von Willebrand factor. In addition, these factors might also form a stronger resistance to cloth lysis with tPA.
Despite having a certain selection of thrombi in this study, e.g., those obtained after successful EVT and selecting thrombi large enough for being homogenized, the study does detect a significant effect.
In conclusion, this study provides additional evidence of a higher platelets content in thrombi being associated with a lower first pass effect rate and a higher number of passes with EVT. These results might also suggest that adjuvant treatments that target platelets could help improve reperfusion therapy in acute ischemic stroke.