Diagnosing cancer-associated ischemic stroke: A systematic review of hematological biomarkers

Patients suffering from cancer are reported to have an increased risk of ischemic stroke (IS). We aimed to identify cancer-associated biomarkers found to differentiate between IS associated with cancer from those not associated with cancer.

We performed a systematic search of PubMed and EMBASE databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study is reported in PROSPERO (#CRD42022355129). In total, 5563 papers were screened, of which 49 papers were included. Seven biomarkers were identified which had the potential to differentiate between patients who had cancer or stroke or both conditions. D-dimer was the most frequently monitored biomarker, and high levels were significantly associated with cancer-related strokes in (42/44) studies. Fibrinogen was significantly associated with cancer-related strokes in 11/27 studies. A higher level of C-reactive protein, investigated in 19 studies, was associated with cancer-related strokes, but conclusive multivariate analysis was not performed. Finally, the four cancer-associated antigens CA125, CA153, CA199, and carcinoembryonic antigen were only reported on in three to six studies, respectively. These studies all originated from the Guangxi province in China. CA125 was associated with an increased risk of IS in four of six studies.

Increased D-dimer seems associated with cancer-related IS. CRP may also be a candidate as a cancer-associated stroke biomarker, but this requires further verification. Fibrinogen and the more specific cancer biomarkers have not yet been proven helpful for detecting cancer-related strokes.