The Role of VWF, FVIII, ADAMTS13 and Inflammatory Response in the Outcome of Acute Ischemic Stroke Mechanical Thrombectomy Procedure

Abstract

Background and Purpose: Mechanical thrombectomy is the method of choice for the intracranial arteries large vessel occlusions therapy in acute ischemic stroke after failed intravenous thrombolysis. Stent retrievers, aspiration catheters or combination are the most often techniques used for the intracranial thrombus extraction. Procedure length, TICI grade of recanalisation and the risk factors like diabetes, hypertension and arhytmia are the critical parameters influencing 3month-mRS clinical outcome after ischemic stroke treatment. Procedure time of the sticky emboli extraction and the endothelial cells damage are influenced with blood coagulation parameters, especially platelet adhesion molecules, D-dimers, fibrinogen, FVIII, von Willebrand factor multimers and by the inflammatory response of the body. Large vWF-multimers are cleaved into smaller, less coagulant forms by the metalloprotease ADAMTS13. In case of ADAMTS13 deficiency, large vWF-multimers are not cleaved from the circulation with the higher risk of thrombosis. Methods: 120 consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Clinical and interventional procedure parameters, as well as blood coagulation factors and cell counts, extracted emboli light microscopy and peripheral blood inflammatory respond were analysed. Results: Significantly higher vWF/ADAMTS13 ratio was found in patients with higher NIHSS in the time of the admission with a worse outcome in 3month-mRS. Extractedvthromboemboli contained significantly higher amount of the inflammatory cells granulocytes, monocytes, vWF/FVIII with fibrin and platelets. Also significantly higher inflammatory respond was observed in patients with NIHSS >15 which correlates with the thromboemboli histology and procedure length prolongation. Conclusion: Platelets, coagulation factors vWF/FVIII and metalloprotease ADAMTS13, in conjunction with inflammatory responsive cells are important factors influencing patient's NIHSS outcome at Day 7 and 3 month after mechanical extraction procedure. High level of the vWF/FVIII and low ADAMTS13 protease activity are responsible for the resistance of the large vessel occlusions to the rt-PA thrombolytic efficacy. The sticky emboli contains red blood cells, fibrin, vWF/FVIII complexes, platelets and inflammation accompanying cells - granulocytes, monocytes and eosinophils. DisclosuresHajek:Novartis: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pharma MAR: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.