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.

Keywords: blood platelets; extracellular traps; fibrin; ischemic stroke; thrombectomy.

Fig.1. PRISMA flow diagram.

Flowchart of the results of the literature search and selection of articles at each stage.

Fig.2. Components of stroke thrombi.

Diagram showing (A) fibrin-rich thrombus and (B) red blood cell-rich thrombus. (A) Fibrin-rich thrombi are composed of platelets-rich zones interspersed in dense fibrin fibres. (B) Red blood cell-rich thrombi are mainly composed of red blood cells with thin fibrin fibres. Clot components are not drawn to scale.

Fig.3. Thrombus evolution with time.

(A) During the initial phases, the thrombus is composed of activated platelets, red blood cells and a porous fibrin mesh. (B) As time progress, platelets contract and red blood cells compress into polyhedrocytes. (C) Activated platelets promotes infiltration of leukocytes including neutrophils into the thrombus forming NETs and stabilising the thrombus with much smaller pores. Clot components are not drawn to scale.

Fig.4. Comparing difference in acute ischaemic stroke treatment between fibrin-rich and red blood cell-rich thrombus.

(A) Fibrin-rich thrombi are more difficult to retrieve using mechanical thrombectomy due to their dense and compact structure. (B) RBC-rich thrombi are easier to retrieve, but more vulnerable to fragmentation. (C) Fibrin-rich thrombi have a poorer infiltration of tPA due to their pores being smaller and more compact. (D) RBC-rich thrombi have an increased sensitivity to tPA due to their looser clot architecture. Clot components are not drawn to scale.