Background: Acute ischemic stroke (AIS) is a significant complication of cancer and may reveal occult malignancy. Whether cancer-related AIS (CAS) provides specific biological features remains unclear.

Objectives: This case-control study aimed to characterize thrombi and plasmas from patients with CAS.

Methods: Nine consecutive patients with CAS, including 3 nonbacterial thrombotic endocarditis (NBTE), and age- and sex-matched AIS controls with cardioembolism (CE, n = 16) or large artery atherosclerosis (LAA, n = 16) were included from the compoCLOT study. Thrombi retrieved after endovascular thrombectomy underwent ex vivo thrombolysis using recombinant tissue-type plasminogen activator and were analyzed for composition. Plasma biomarkers were also assessed.

Results: CAS thrombi were resistant to tissue-type plasminogen activator lysis compared with LAA thrombi (median thrombus weight conservation, 92% vs 9%; P = .0002) and, to a lesser extent, compared with CE thrombi (92% vs 43%; P = .06). Thrombolysis resistance correlated negatively with red blood cell content (P < .0001) but positively with platelet factor-4 (P = .0014), von Willebrand factor (P = .0002) and DNA content (P < .0001). A subgroup of macroscopically white thrombi (n = 6), characterized by low red blood cell and high von Willebrand factor content, was identified in CAS, encompassing all 3 NBTE cases. Plasma D-dimer, fibrin monomers, extracellular vesicle-associated tissue factor and myeloperoxidase were significantly higher in patients with CAS than in the combined LAA and CE control groups (31,290 vs 1900 µg/L; 143 vs 9 μg/mL; 143 vs 9 fM; and 51 vs 25 ng/mL, respectively).