AUTHOR=Marta-Enguita Juan , Navarro-Oviedo Manuel , Muñoz Roberto , Olier-Arenas Jorge , Zalba Guillermo , Lecumberri Ramon , Mendioroz Maite , Paramo Jose A. , Roncal Carmen , Orbe Josune 

TITLE=Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.599498

DOI=10.3389/fneur.2021.599498

ISSN=1664-2295

ABSTRACT=Actual clinical management of Ischemic Stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of haemostatic parameters such as thrombin activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remain unknown, despite their presence could determine thrombus stability and its response to thrombolytic treatment improving patient’s outcome. We collected thrombi (n=45) from Large Vessel Occlusion (LVO) stroke patients (n=53) and performed a histological analysis of different haemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, and TAFI and VWF activity and recorded clinical variables. In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localised in regions of inflammatory cells, surrounded by erythrocyte and platelet rich areas. The content of MMP-10 and TAFI was significantly associated (r=0.41 p<0.01), being TAFI lower in patients who died during the first 3 months after stroke onset [OR (95%CI); 0.59 (0.36-0.98), p=0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r=-0.30, p<0.05). Besides, VWF was associated with the presence of leukocytes (r=0.37 p<0.05), platelets (r=0.32, p<0.05), and mortality at 3 months mortality [OR (95%CI); 4.5 (1.2-17.1), p=0.029]. Finally, plasma levels of TAFI were correlated with circulating and thrombus platelets while, plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months. The present study suggests that the composition and distribution of thrombus haemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.