Thrombus Composition and Efficacy of Thrombolysis and Thrombectomy in Acute Ischemic Stroke

Abstract

Thrombi retrieved from patients with acute ischemic stroke are highly heterogeneous. Recent data suggest that thrombus composition may impact on mechanical thrombectomy, the number of recanalization manoeuvres, resistance to retrieval, and on thrombolytic potential. Our aim was to summarize evidence describing the impact of thrombus composition on efficacy of mechanical thrombectomy and thrombolysis in patients with acute ischemic stroke. The scoping review methodology guided by the Joanna Briggs Institute, an adaption of the Arksey and O’Malley, was followed. Comprehensive searches were conducted in MEDLINE, EMBASE, SCOPUS, and Web of Science. Articles were classified into 4 key themes: (1) composition of stroke thrombi, (2) thrombus composition and mechanical thrombectomy, (3) thrombus composition and thrombolytic therapy, and (4) novel imaging and endovascular approaches. Our search identified 698 articles published from 1987 to June 2020. Additional articles were extracted from reference lists of the selected articles. Overall, 95 topic-specific articles identified for inclusion published in 40 different journals were included. Reports showed that thrombus composition in stroke was highly heterogeneous, containing fibrin, platelets, red blood cells, VWF (von Willebrand Factor), and neutrophil extracellular traps. Thrombi could roughly be divided into fibrin- and red blood cell–rich clots. Fibrin-rich clots were associated with increased recanalization manoeuvres, longer procedure time, and less favorable clinical outcomes compared with red blood cell–rich clots. Advances in detection or treatment of thrombi that take into account clot heterogeneity may be able to improve future endovascular and thrombolytic treatment of stroke.

Mechanical Thrombectomy in Acute Terminal Internal Carotid Artery Occlusions Using a Large Manually Expandable Stentretriever (Tiger XL Device): Multicenter Initial Experience

“…It is known that intracranial thrombus morphology and composition undergoes time-dependent changes, which include proximal and distal apposition as well as a progressive fibrin network propagation (fibrin-rich white clot) [18]. Fibrin-rich and longer clots are associated with increased reperfusion maneuvers, longer procedure time, less favorable clinical outcomes and reperfusion failures compared with red blood cell-rich clots following two recently published studies [19,20].…”

A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis

“…Recent studies indicated a new model of stroke thrombus evolution, where, as the last step in the process of thrombi ageing, neutrophils infiltrate the thrombus by forming NETs and stabilize the thrombus with much smaller pores 23 . In fact, clot dissolution by rt-PA is the easiest in the early stages of thrombus formation, when the cross-linking of fibrin and fibrinolysis inhibitors to fibrin by activated factor XIII has not yet taken place, and the clot is less compact with larger pores.…”

“…This could be an important aspect in clinical scenarios when thrombolysis is applied before mechanical thrombectomy. Recent guidelines propose that intravenous rt-PA should be considered for eligible patients even if mechanical thrombectomy is used 23 – 28 . To improve the safety of this approach, novel tests, such as the modified CLA might prove to be useful in the future.…”

A Thrombectomy Model Based on Ex Vivo Whole Human Brains

“…This clot analog was selected to challenge current thrombectomy devices because fibrin-rich clots have been reported to be associated with more device passes, longer procedure times, and less favorable patient outcomes. 8 Clot analogs with different histology and tensile properties can also be made by mixing human plasma and red blood cells with different volume ratios. 7,9 Thrombectomy Testing Thrombectomy was performed with a 6F catheter (Sofia Plus; MicroVention) using the direct-aspiration technique or in combination with a stent retriever (Solitaire; Medtronic) using the Solumbra technique.…”