Relationships Between D-Dimer Levels and Stroke Risk as Well as Adverse Clinical Outcomes After Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

Abstract

Objective: Abnormal elevation of D-dimer levels is an important indicator of disseminated intravascular clotting. Therefore, we hypothesized that high D-dimer levels were associated with the risk of stroke and adverse clinical outcomes of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).Methods: The present meta-analysis aimed to systematically analyze the associations between D-dimer and the risk of stroke as well as the clinical outcomes of patients with post-stroke or TIA. Meanwhile, dose–response analyses were conducted when there were sufficient data available. Three electronic databases including Pubmed, the Embase database, and the Cochrane Library were searched by two investigators independently. All the pooled results were expressed as risk ratios (RRs).Results: Finally, 22 prospective cohort studies were included into this meta-analysis. The results suggested that high D-dimer levels were associated with increased risks of total stroke (RR 1.4, 95%CI 1.20–1.63), hemorrhagic stroke (RR 1.25, 95%CI 0.69–2.25), and ischemic Stroke (RR 1.55, 95%CI 1.22–1.98), and the dose-dependent relationship was not found upon dose–response analyses. Besides, the high D-dimer levels on admission were correlated with increased risks of all-cause mortality [RR 1.77, 95% confidence interval (CI) 1.26–2.49], 5-day recurrence (RR 2.28, 95%CI 1.32–3.95), and poor functional outcomes (RR 2.01, 95%CI 1.71–2.36) in patients with AIS or TIA.Conclusions: On the whole, high D-dimer levels may be associated with the risks of total stroke and ischemic stroke, but not with hemorrhagic stroke. However, dose–response analyses do not reveal distinct evidence for a dose-dependent association of D-dimer levels with the risk of stroke. Besides, high D-dimer levels on admission may predict adverse clinical outcomes, including all-cause mortality, 5-day recurrence, and 90-day poor functional outcomes, of patients with AIS or TIA. More studies are warranted to quantify the effect of D-dimer levels on the risk of stroke or TIA, so as to verify and substantiate this conclusion in the future.

A Systematic Review of Body Fluids Biomarkers Associated With Early Neurological Deterioration Following Acute Ischemic Stroke

“…Barber et al (2006) confirmed that D-dimer was an independent predictor of AIS progression using three different measurement methods ( Barber et al, 2006 ). Furthermore, A recent meta-analysis demonstrated that high D-dimer levels on admission significantly increased the risk of recurrence on the 5-day diffusion-weighted imaging (DWI) in AIS patients ( Yuan et al, 2021 ). As previous research noted, elevated D-dimer levels may reflect the ongoing or potential thrombosis and hypercoagulability ( Haapaniemi and Tatlisumak, 2009 ).…”

The correlation of D‐dimer to stroke diagnosis within 24 hours: A meta‐analysis

“… 23 , 24 , 25 Yuan and colleagues analyzed the associations between D‐Dimer and the risk of stroke (i.e., pre‐stroke) employing a sample set of 22,590 patients. 22 The authors found that the D‐Dimer levels increased the risk of total stroke by 40% (RR = 1.4, 95% CI = 1.2–1.63). 22 In our study, we found a large positive effect size of D‐Dimer levels among patients who were diagnosed with stroke using laboratory testing as an adjuvant to imaging findings (Cohen's d = 2.82, 95% CI = 1.73–3.9).…”

“… 22 The authors found that the D‐Dimer levels increased the risk of total stroke by 40% (RR = 1.4, 95% CI = 1.2–1.63). 22 In our study, we found a large positive effect size of D‐Dimer levels among patients who were diagnosed with stroke using laboratory testing as an adjuvant to imaging findings (Cohen's d = 2.82, 95% CI = 1.73–3.9). Yuan et al also noted that when the D‐Dimer level increased by 50 ng/ml, the risk of stroke increased by 0.3%.…”

“…In clinical practice, abnormal D‐Dimer plasma levels are used as important predictors of disseminated intravascular clotting, and low levels are often used to rule out critical events such as pulmonary embolism and deep venous thrombosis. 22 Very few studies assess the role of D‐Dimer with the risk of stroke of adverse clinical outcomes post‐stroke.…”

“…Yuan et al also noted that when the D‐Dimer level increased by 50 ng/ml, the risk of stroke increased by 0.3%. 22 …”