Clot signature in patients with large vessel occlusion stroke and concomitant active cancer

Abstract

Background and purpose: Patients with active cancer face an increased risk of ischemic stroke. Also, stroke may be an initial indicator of cancer. In patients with large vessel occlusion (LVO) stroke treated with thrombectomy, analysis of the clot composition may contribute new insights into the pathological connections between these two conditions.

Methods: We compared the content of 64 consecutively retrieved clots from LVO stroke patients with concomitant active cancer and 64 clots from matched-control LVO stroke patients without a history of cancer. Clots were analyzed with respect to histological composition by Martius Scarlet Blue, von Willebrand factor (vWF), citrullinated histone H3 (H3Cit, a biomarker of NETS), CD42b, and CD3 expression by immunohistochemistry. Orbit Image Analysis was used for quantification. Differences between groups were tested using the Mann-Whitney U-test and Chi-square Test.

Results: Clots from patients with concomitant cancer had a significantly higher content of vWF (median 26 [IQR13-38]% vs. 10 [4-18]%, p < 0.0001) and H3Cit (median 0.11 [IQR0.02-0.46]% vs. 0.05 [0.00-0.28]% p = 0.027) than controls. The presence of collagen >1% within the retrieved clots was highly indicative of cancer, occurring in 16/64 with active cancer and in 3/64 controls, p = 0.002. After correction for multiple comparisons, the statistical significance for H3Cit was lost. Red and white blood cells, platelets, fibrin, and expression of CD3 and CD42b did not differ between the groups.

Conclusions: Clots from LVO patients with concomitant active cancer possess distinct characteristics, indicating an influence of cancer on the innate immune system, fibroblasts, and the vascular endothelium in the formation of LVO clots.

Keywords: NETS; acute ischemic stroke & cancer; clot composition; collagen; vWF.