{
  "abstract": "Background Thrombus composition influences response to thrombolysis in acute ischemic stroke (AIS). However, the histologic phenotype of residual clot tissue following thrombolysis (representing the parts with the highest resistance) remains poorly defined.Objective To characterize the composition of residual thrombus after ex vivo tissue-plasminogen activator (tPA) exposure and to evaluate compositional changes using exploratory comparisons of fragments derived from the same clots that were not exposed to tPA.Methods Retrieved stroke thrombi underwent Martius Scarlet Blue staining with quantitative assessment of fibrin, red blood cells (RBCs), platelets, and white blood cells (WBCs). Clot fragments exposed to tPA were analyzed after 3.5 hours. Fragments from the same clot that were not exposed to tPA were also analyzed (these were dissected haphazardly and evaluated as exploratory same-parent comparisons rather than true matched baselines). Thrombolysis rates at 1 and 3.5 hours were calculated as percentages of weight loss relative to baseline weight of the exposed clot fragments. Results are reported as median (interquartile range [IQR]). Paired comparisons were performed using the Wilcoxon signed-rank test. Associations between continuous variables were assessed using Spearman rank correlation, reported as Spearman’s rho (ρ). Two-sided p-values (p) <0.05 were considered statistically significant. Because only exposed fragments had recorded weights, weight-adjusted residual component burden was calculated within exposed clots only as 3.5-hour clot weight multiplied by post-tPA histologic composition, and its association with thrombolysis was evaluated using Spearman correlation.Results Fifty-six clots had thrombolysis data, with complete post-tPA histologic quantification and 26 with exploratory same-parent exposed/non-exposed comparisons. Residual thrombus after 3.5 hours of tPA exposure demonstrated a fibrin- and platelet-dominant phenotype, with fibrin 59.93% (41.79-71.78), platelets 30.61% (18.30-50.86), RBCs 0.28% (0.06-2.98), and WBCs 0.99% (0.50-2.63). Median thrombolysis was 4.61% (0.00-24.28) at 1 hour and 22.41% (6.06-38.25) at 3.5 hours. Exposed clot weight decreased from 0.0206 g (0.0146-0.0304) at baseline to 0.0156 g (0.0099-0.0228) at 3.5 hours (p<0.0001). In exploratory same-parent comparisons (n = 26), RBC proportion was significantly lower in exposed fragments than in non-exposed fragments (0.14% [0.05-2.61] vs 3.11% [0.40-14.25], p=0.012), whereas platelet (39.77% [20.08-55.13] vs 21.53% [14.03-49.02], p=0.143), fibrin (50.36% [40.79-67.24] vs 54.10% [37.84-73.58], p=0.803), and WBC (1.25% [0.70-2.74] vs 1.36% [0.64-2.50], p=0.452) proportions did not significantly differ. Within exposed clots, greater residual fibrin burden was associated with lower thrombolysis at 1 hour (ρ=-0.273, p=0.0415) and 3.5 hours (ρ=-0.360, p=0.00635), and greater residual platelet burden was associated with lower thrombolysis at 1 hour (ρ=-0.340, p=0.0104) and 3.5 hours (ρ=-0.401, p=0.00222). Residual RBC and WBC burdens were not associated with thrombolysis.Conclusions Residual thrombus following tPA exposure is characterized by marked depletion of RBC-rich regions and significant reduction in fibrin burden, with preservation of platelet-rich structure. Apparent platelet enrichment reflects relative preservation rather than true accumulation. These findings support a model in which thrombolysis preferentially removes RBC- and fibrin-rich components while leaving a platelet-dominant scaffold associated with reduced thrombolytic efficacy.Disclosures A. Mohammed: None. O. Mereuta: None. F. Alsereidi: None.",
  "authors": [
    {
      "affiliations": [
        "Neurologic Surgery, Mayo clinic, Rochester, MN"
      ],
      "name": "A Mohammed"
    },
    {
      "affiliations": [
        "Radiology, Mayo Clinic, Rochester, MN"
      ],
      "name": "O Mereuta"
    },
    {
      "affiliations": [
        "Neurologic Surgery, Mayo clinic, Rochester, MN"
      ],
      "name": "F Alsereidi"
    },
    {
      "affiliations": [
        "Mayo Clinic, Rochester, MN"
      ],
      "name": "R Kadirvel"
    }
  ],
  "title": "O-001 Histologic composition of residual stroke thrombus after ex vivo thrombolysis with tissue-plasminogen activator",
  "uid": "8515aebd-3191-51c1-8c88-3076308a2263"
}