CD163-positive macrophages were significantly more enriched in thrombi from atrial fibrillation patients than in those from sinus rhythm.

Plasma levels of soluble CD163 paralleled thrombus CD163 expression, suggesting potential utility as a circulating biomarker for thrombus origin.

This is the first study to pathologically compare cardiogenic and atherosclerotic thrombi, identifying CD163 as a candidate marker for differentiating thrombus etiology.

Differentiating between atherosclerotic and cardiogenic thrombi remains a clinical challenge and complicates the optimal selection of antithrombotic therapy for secondary prevention.

This study aimed to investigate histopathological differences between thrombi presumed to be of atherosclerotic (sinus rhythm, SR) and cardiogenic (atrial fibrillation, AF) origin.

The Macrophage in Thrombus (MITO) study is a prospective observational study of patients with ST-elevation myocardial infarction (STEMI) or embolic stroke (ES), in whom solid thrombi were retrieved from infarct-related arteries. Patients were categorized into two groups: Group SR (presumed atherosclerotic thrombi) and Group AF (presumed cardiogenic thrombi). Thrombi were immunohistochemically stained for CD163-positive macrophages, scored on a three-point scale, score 1: no CD163-positive cell detectable at ×400; score 2: the cell detectable at ×400 but not ×100; score 3: easy to detect the cell in ×100 in the thrombus. Also, soluble CD163 was measured in plasma samples.

The scores of Group SR were significantly lower than those of Group AF (p < 0.01). Plasma level of soluble CD163 (ng/mL) in Group SR was significantly lower than in Group AF [487 (275, 636) vs. 630 (472,780), p = 0.04].

The distribution of CD163-positive cells differed between thrombi from Group SR and Group AF patients. These findings suggest a role for CD163-positive macrophages in the pathogenesis of cardiogenic thrombi and raise the possibility of CD163 as a biomarker for thrombus etiology.

ESUS

thrombus

Pathology

Biomarker

Brain natriuretic peptide

Cluster of differentiation

Embolic stroke of undetermined source

Percutaneous coronary intervention

ST elevation myocardial infarction

© 2025 The Authors. Published by Elsevier B.V.