Mechanisms of fibrinolysis resistance and potential targets for thrombolysis in acute ischaemic stroke: lessons from retrieved stroke emboli

• Authors: Waleed Brinjikji, Mayo Clinic, Rochester; Oana Madalina Mereuta, Mayo Clinic, Rochester; Daying Dai, Mayo Clinic, Rochester; David F Kallmes, Mayo Clinic, Rochester; Luis Savastano, Mayo Clinic, Rochester; Yang Liu, Mayo Clinic, Rochester; Shahid M Nimjee, Ohio State University; Raul Nogueira, Emory University; Mehdi Abbasi, Mayo Clinic, Rochester; Ramanathan Kadirvel, Mayo Clinic, Rochester
• Journal Title: STROKE AND VASCULAR NEUROLOGY
• Volume: Volume 6, Number 4
• Publisher: BMJ PUBLISHING GROUP | 2021-07-26, Pages 658-667
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1136/svn-2021-001032
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; stroke; thrombectomy; thrombolysis; NEUTROPHIL EXTRACELLULAR TRAPS; CLOTS; TENECTEPLASE; CONTRACTION; OCCLUSION; CT

Abstract

There has been growing interest and insight into the histological composition of retrieved stroke emboli. One of the main focuses of the stroke clot analysis literature has been the implications of clot composition on mechanical thrombectomy procedures. However, the holy grail of clot analysis may not be in the field of clot-device interaction, but rather, in understanding mechanisms of fibrinolysis resistance. The mechanisms underlying the low response to fibrinolytic therapy, even with the newer, more powerful agents, remain poorly understood. While factors such as embolus size, location and collateral status influence alteplase delivery and recanalisation rates; compositional analyses focused on histological and ultrastructural characteristics offer unique insights into mechanisms of alteplase resistance. In this review, we strive to provide comprehensive review of current knowledge on clot composition and ultrastructural analyses that help explain resistance to fibrinolysis.