Novel human acute ischemic stroke blood clot analogs for in vitro thrombectomy testing

Fitzgerald, Seán, Liu, Yang, Dai, Daying, Mereuta, Oana Madalina, Abbasi, Mehdi, Larco, JL Arturo, Douglas, Andrew, Kallmes, David, Savastano, Luis, Doyle, Karen M., Brinjikji, Waleed. (2021). Novel Human Acute Ischemic Stroke Blood Clot Analogs for In Vitro Thrombectomy Testing. American Journal of Neuroradiology. doi:10.3174/ajnr.A7102

Abstract

BACKGROUND AND PURPOSE: Previous studies have successfully created blood clot analogs for in vitro endovascular device testing using animal blood of various species. Blood components vary greatly among species; therefore, creating clot analogs from human blood is likely a more accurate representation of thrombi formed in the human vasculature. MATERIALS AND METHODS: Following approval from the Mayo Clinic institutional review board, human whole-blood and platelet donations were obtained from the blood transfusion service. Twelve clot analogs were created by combining different ratios of red blood cells + buffy coat, plasma, and platelets. Thrombin and calcium chloride were added to stimulate coagulation. Clot composition was assessed using histologic and immunohistochemical staining. To assess the similarities of mechanical properties to patient clots, 3 types of clot analogs (soft, elastic, and stiff) were selected for in vitro thrombectomy testing. RESULTS: The range of histopathologic compositions produced is representative of clots removed during thrombectomy procedures. The red blood cell composition ranged from 8.9% to 91.4%, and fibrin composition ranged from 3.1% to 53.4%. Platelets (CD42b) and von Willebrand Factor ranged from 0.5% to 47.1% and 1.0% to 63.4%, respectively. The soft clots had the highest first-pass effect and successful revascularization rates followed by the elastic and stiff clots. Distal embolization events were observed when clot ingestion could not be achieved, requiring device pullback. The incidence rate of distal embolization was the highest for the stiff clots due to the weak clot/device integration. CONCLUSIONS: Red blood cell–rich, fibrin-rich, and platelet-rich clot analogs that mimic clots retrieved from patients with acute ischemic stroke were created in vitro. Differing retrieval outcomes were confirmed using in vitro thrombectomy testing in a subset of clots.

Funder

European Regional Development Fund
Science Foundation Ireland
National Institutes of Health
Enterprise Ireland

Publisher

American Society of Neuroradiology

Rights

Attribution-NonCommercial-NoDerivs 3.0 Ireland

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Collections

Physiology (Scholarly Articles)