Search

Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes.During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables.Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke.

Objective The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. Methods We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. Results Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). Interpretation Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.

Introduction: We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS. Methods: In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes. Results: Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS. Conclusion: Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.