Abstract Body: Background: Patients with active cancer and ischemic stroke have significantly higher morbidity and mortality compared to stroke patients without cancer. Elevated d-dimer levels are a key finding for determining cancer coagulopathy as the likely etiology for stroke. Studies that examined d-dimer as a surrogate marker of outcomes in cancer-associated stroke are limited by small sample sizes. Our objective was to conduct a systematic review & meta-analysis for the prognostic value of serum d-dimer measured at the time of ischemic stroke in cancer patients. We hypothesize that high d-dimer is associated with high rates of recurrent stroke, death, & poor functional outcomes.

Methods: MEDLINE, Embase, and the Web of Science were searched (until July 2024) for cohort studies of patients with cancer-associated ischemic stroke that assessed the prognostic value of elevated d-dimer levels (measured at the time of stroke onset) for recurrent stroke, mortality, and poor functional outcome (modified Rankin Scale [mRS] score of 3-6). For the primary analysis, we conducted meta-analyses of median differences in d-dimer levels between patients with vs. without the outcomes of interest, using the random-effects method. Meta-analyses of studies reporting odds ratios or hazard ratios could not be performed due to the variable d-dimer cutoffs used across the studies; associations from these studies are summarized narratively.

Results:
From 4522 titles, there were 19 eligible studies. Elevated serum d-dimer was significantly associated with an increased risk of recurrent stroke (pooled median difference 14.54 [95% CI, 2.09 to 26.99], p=0.022), and mortality (pooled median difference, 11.18 [95% CI, 9.67 to 12.70], p<0.001). There was no association between d-dimer level and poor functional outcome (pooled median difference, 0.76 [95% CI, -1.71 to 3.24], p=0.55; Figure 1). The forest plot for individual studies studying mortality is shown in Figure 2; visual inspection suggests that those with higher d-dimer levels have higher risks of mortality.

Conclusion:
Elevated serum d-dimer measured at the time of ischemic stroke onset in patients with active cancer may identify those at high risk of recurrent stroke and mortality, though our study is limited by the small number of pooled studies and low individual study sample sizes. Nevertheless, they could support routine clinical use of d-dimer to identify high-risk patients for enrolment in secondary prevention trials.