DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause
Lucas Di Meglio, Jean‐Philippe Desilles, Mialitiana Solonomenjanahary, Julien Labreuche, Véronique Ollivier, Sébastien Dupont, Catherine Deschildre, Malek Ben Maacha, Arturo Consoli, Bertrand Lapergue, Michel Piotin, Raphaël Blanc, Benoît Ho‐Tin‐Noé, Mikaël Mazighi, Jean‐Philippe Desilles, Hocine Redjem, Stanislas Smajda, Gabriele Cicciò, Simon Escalard, François Delvoye, Benjamin Maïer, Solène Hébert, Mylène Hamdani, Candice Sabben, Michaël Obadia, Georges Rodesch, Federico Di Maria, Okuzan Coskun, Delphine Lopez, Romain Bourcier, Lili Détraz, Hubert Desal, Monica Roy, Delphine Clavier, Gaultier Marnat, Florent Gariel, Ludovic Lucas, Igor Sibon, François Eugène, Stéphane Vannier, Jean‐Christophe Ferré, Anthony Le Bras, Hélène Raoult, Christophe Paya, Jean‐Yves Gauvrit, Sébastien Richard, Benjamin Gory, Charlotte Barbier, Denis Vivien, Emmanuel Touzé, Maxime Gauberti, Gaëtane Blaizot
Abstract
BACKGROUND AND PURPOSE: Identification of acute ischemic stroke (AIS) cause is crucial for guidance of secondary prevention. Previous studies have yielded inconsistent results regarding possible correlations between AIS cause and thrombus composition, as assessed by semiquantitative histological analysis. Here, we performed a correlation analysis between AIS cause and AIS thrombus cellular composition and content, as assessed using quantitative biochemical assays. METHODS: Homogenates of 250 patients with AIS thrombi were prepared by mechanical grinding. Platelet, red blood cell, and leukocyte content of AIS thrombi were estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. AIS cause was defined as cardioembolic, noncardioembolic, or embolic stroke of undetermined source, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment). RESULTS: =0.045) than noncardioembolic ones. The area under the receiver operating characteristic curve of DNA content to discriminate cardioembolic thrombi from noncardioembolic was 0.72 (95% CI, 0.63-0.81). With a threshold of 44.7 ng DNA/mg thrombus, 47% of thrombi from undetermined cause would be classified as cardioembolic with a specificity of 90%. CONCLUSIONS: Thrombus DNA content may provide an accurate biomarker for identification of cardioembolic thrombi in patients with AIS with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03268668.