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DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause
Lucas Di Meglio1,2, Jean-Philippe Desilles1,2, Mialitiana Solonomenjanahary1
1Univ de Paris, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France (L.D.M., J.-P.D., M.S., V.O., S.D., C.D., B.H.-T.-N., M.M.).
Insights
Thrombus DNA content can help identify the cause of acute ischemic stroke (AIS). Higher DNA levels in AIS thrombi may indicate a cardioembolic source, aiding secondary prevention strategies.
Area of Science:
- Biochemistry
- Neurology
- Cardiology
Background:
- Identifying the cause of acute ischemic stroke (AIS) is critical for effective secondary prevention.
- Previous research on thrombus composition and AIS etiology has produced conflicting findings.
- Quantitative biochemical assays offer a novel approach to analyze thrombus cellular content.
Purpose of the Study:
- To investigate the correlation between the cause of AIS and the cellular composition of AIS thrombi.
- To assess thrombus composition using quantitative biochemical assays.
- To determine if thrombus composition can predict the stroke's underlying cause.
Main Methods:
- Analyzed 250 AIS thrombi using mechanical grinding to prepare homogenates.
- Quantified platelet, red blood cell, and leukocyte content via GPVI, heme, and DNA measurements.
- Classified AIS etiology using the TOAST criteria (cardioembolic, noncardioembolic, undetermined source).
Main Results:
- Cardioembolic thrombi showed significantly higher DNA content (35.8 ng/mg vs. 13.8 ng/mg, P<0.001) and lower GPVI (0.104 ng/mg vs. 0.117 ng/mg, P=0.045) compared to noncardioembolic thrombi.
- DNA content demonstrated moderate accuracy in discriminating cardioembolic from noncardioembolic thrombi (AUC=0.72).
- A DNA threshold of 44.7 ng/mg classified 47% of undetermined source thrombi as cardioembolic with 90% specificity.
Conclusions:
- Thrombus DNA content serves as a potential biomarker for identifying cardioembolic sources in AIS.
- This finding can improve etiological classification for patients with embolic stroke of undetermined source.
- Accurate etiological diagnosis facilitates tailored secondary prevention strategies for AIS patients.
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:
Cardioembolic thrombi were richer in DNA (35.8 versus 13.8 ng/mg, P<0.001) and poorer in GPVI (0.104 versus 0.117 ng/mg, P=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.
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