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Editorials
thrombus composition and their mechanical properties, which would be advantageous in guiding the develop- ment of new generations of stent retrievers, as well as the selection of optimal thrombectomy therapy for patients. Another limitation of current studies regards the handling and storage of thrombus samples from patients. The thrombi obtained from thrombectomy are likely to undergo structural changes during or after the retrieval process. It is usually not possible to tell if the whole clot has been retrieved, or only fragments of it, and which parts represent the ‘head’ of the clot or the ‘tail’. Furthermore, the internal organization and composition are probably modified by chemical fixation, air exposure or physical manipulation. A standard thrombus process- ing method needs to be developed to standardize those influences on thrombi during and after the retrieval process.19,20 In addition, the thrombi analyzed in this study only represent those that were successfully retrieved by thrombectomy, and were obtained from patients who received either prior rt-PA treatment or not. Future histological studies focusing on thrombi that are resistant to thrombectomy and rt-PA treatment would open a new window for advancing the treatment of acute ischemic stroke using intravascular approaches.
Intriguing new questions are also raised by the current study. For example, the role of polyhedrocytes observed in the thrombus remains poorly characterized. Polyhedrocytes are formed in contracted blood clots and thrombi due to the compression by activated contractile platelets pulling on fibrin. Remarkably, polyhedrocytes were first described in German by Gottlob et al. In 1970,21 Cynes et al. further characterized polyhedral erythrocytes, and described their occurrence in clots made in vitro and in thrombi obtained by thrombectomy from patients with myocardial infarction.15,16,22 The occurrence of poly- hedrocytes in coronary thrombi was independently con- firmed by Zalewski et al.23 These studies suggest that polyhedrocytes play important roles in thrombi, by form- ing a near impermeable seal that impairs diffusion of fib- rinolytic enzymes into thrombi, leading to reduced thrombolysis. However, despite the multiple observa- tions and efforts made by previous studies, detailed mechanisms of polyhedrocyte formation in contracted thrombi and their clinical and pathological implications are still underappreciated. Furthermore, thrombus con- traction, usually associated with the presence of polyhe- drocytes, is another interesting topic. It has been reported that patients with VTE and PE have significantly reduced
Figure 1. Schematic representation of the composition and organization of ischemic stroke thrombi as reported by Staessens et al.6 (Top) Red blood cell (RBC) rich area. This area mainly consists of packed RBC (polyhedrocytes) surrounded by thin fibrin fibers, which fill (or ‘cement’) the space between cells. Leukocytes (neutrophils) are also observed in these areas, but are less abundant. (Bottom) Platelet-rich area. Multiple structural components are found in this area, including platelets, thick fibrin bundles, von Willebrand factor (vWF), leukocytes (neutrophils) and extracellular DNA (due to NETosis).
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haematologica | 2020; 105(2)