Aurora Semerano, MD
Cancer has recently emerged as a significant risk factor for arterial thromboembolism, including ischemic stroke.1 Currently, one in ten patients with ischemic stroke have comorbid cancer.2 Moreover, among ischemic stroke patients, comorbid cancer is associated with increased stroke severity, disability, and mortality. The optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established, with high recurrence rates despite antithrombotic therapies, and there are currently limited resources to assist stroke clinicians in the management of cancer patients. Histological analysis of the arterial cerebral thrombi retrieved in endovascular thrombectomy may provide new insights into the pathogenesis of stroke-related cancer.
In this brief report published in Stroke, Fu et al.3 analyzed the composition of 19 cerebral thrombi retrieved in stroke patients with active cancer and compared them with thrombi of cardioembolic (n=107) and large artery atherosclerosis (n=26) etiology. After staining thrombus sections with hematoxylin and eosin (H&E), they used an image analysis software for the quantification of the following thrombus components: fibrin/platelets, red blood cells, and white blood cells. They found higher fibrin/platelet and lower red blood cell proportions in thrombi from patients with active cancer compared to cardioembolic and atherothrombotic clots, and they identify an optimal cut-off value of fibrin/platelet percentage of >65% to distinguish cancer from the other etiologies (AUC 0.84). In thrombi from patients with active cancers, they also employed an anti-CD42b immunohistochemistry stain to highlight platelet-rich areas and found that the proportion of CD42b positive area was higher in patients with adenocarcinoma compared to the non-adenocarcinoma group.
This is one of the first studies investigating the composition of cerebral thrombi in cancer patients. Importantly, the main finding of the study is confirmed after a multivariable analysis taking into account patient baseline characteristics, which is important in the heterogeneous stroke population. Some limitations can also be traced. In the article, the authors mainly used H&E staining for their composition analysis, which does not adequately distinguish platelets from fibrin, limiting the insights on cancer-related stroke pathogenesis. Another recent study4 investigated thrombus composition in cancer patients and quantified thrombus components by immunochemistry staining with antibodies against CD42b (for platelets), glycophorin A (for red blood cells) and fibrinogen (for fibrin/fibrinogen). They found that patients with active cancer had thrombi rich in platelets and poor in red blood cells compared to patients with inactive cancer or without any cancer; however, the percentage of fibrin did not differ between the three groups. This may suggest that platelet enrichment of the clots, more than fibrin, could represent a marker of cancer-related thrombosis. However, further studies with larger cohorts are needed to provide useful information for an effective treatment strategy in these patients. Several mechanisms of cancer-mediated hypercoagulability have been proposed, though yet under investigation, including cancer cell-derived extracellular vesicles triggering thrombosis, platelet activation, unbalance of procoagulant/fibrinolysis factors, and activation of immune mechanisms of thrombo-inflammation. Cancer heterogeneity (that’s to say the wide spectrum of histological cancer types, as well as the different phases of cancer) may also account for this variety of mechanisms and will be another important factor to consider in future studies on cancer-related stroke.
1 Navi BB, Iadecola C. Ischemic stroke in cancer patients: A review of an underappreciated pathology. Ann Neurol. 2018;83:873-883.
2 Sanossian N, Djabiras C, Mack WJ, Ovbiagele B. Trends in cancer diagnoses among inpatients hospitalized with stroke. J Stroke Cerebrovasc Dis. 2013;22:1146-50.
3 Fu CH, Chen CH, Lin YH, Lee CW, Tsai LK, Tang SC, Shun CT, Jeng JS. Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer. Stroke. 2020;51:3723–3727.
4 Park H, Kim J, Ha J, Hwang IG, Song TJ, Yoo J, Ahn SH, Kim K, Kim BM, Kim DJ, Kim YD, Nam HS, Kwon I, Choi HJ, Sohn SI, Lee HS, Heo JH. Histological features of intracranial thrombi in stroke patients with cancer. Ann Neurol. 2019;86:143-149.