High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

Abstract

Background: D-dimer is a fibrin degradation product and a possible marker of thromboembolic events. The aim of this study was to investigate the relationship between D-dimer levels and outcome in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis. Methods: This retrospective study included AIS patients who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and provided plasma D-dimer level within 24 h after stroke onset during 2009 and 2014 at a single medical center. Unfavorable outcome was defined as modified Rankin scale ≥3 at 3 months after stroke. Symptomatic intracerebral hemorrhage (ICH) was defined as a deterioration of at least 4 points on the National Institutes of Health Stroke Scale within 36 h post thrombolysis. Results: Of 347 patients receiving intravenous rt-PA, 159 (mean age 67.6 ± 13.1 year, 59.7% male) fulfilled the inclusion criteria. In univariate analysis, patients with unfavorable outcome (n = 79) had significantly higher levels of D-dimer than those with favorable outcome (median ln D-dimer = 1.4 vs. 0.7 μg/ml, p < 0.001). After adjustment for clinical variables, a higher level of D-dimer remained significantly associated with an unfavorable outcome (OR 1.90, 95% CI 1.27-2.86, p = 0.002) and the occurrence of symptomatic ICH (OR 2.97, 95% CI 1.15-7.70, p = 0.025). Conclusion: The D-dimer level within 24 h after stroke onset can be an early outcome indicator in AIS patients receiving rt-PA therapy.

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

“…Especially D-dimer was effective in identifying IS etiology [181,182] and showed good prognostic accuracy as predictor of short- and long-term worse outcome [182,183,185,186]. Similar results were also reported for E-selectin and VCAM-1, but those data required further validation in additional large-cohort studies [184].…”

“…Furthermore, specific challenges regarding biomarkers of central nervous tissue include the penetration of BBB and the lack of correlation between functional symptoms and volume (as opposed to location) of injured tissue. According to pathophysiological processes underlying IS, potential inflammatory biomarkers may be classified as released by: (i) astroglial activation and neuronal injury (Table 1) [146,147,148,149,150,151,152,153,154,155,156,157]; (ii) systemic inflammatory response (Table 2) [158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179]; (iii) dysfunctional endothelium (Table 3) [180,181,182,183,184,185,186] (Figure 4). …”

Thromboelastography‑derived parameters for the prediction of acute thromboembolism following non‑steroidal anti‑inflammatory drug‑induced gastrointestinal bleeding: A retrospective study

“…D-dimer, is a well characterized sensitive marker of thrombosis with fiber dissolving activity (49), which had a predictive value for AT in patients with NSAID-induced GIB in the present study. D-dimer is a degradation product produced during the hydrolysis of fibrinolytic enzymes and is a specific indicator of hypercoagulability and secondary fibrinolysis (49). Secondary fibrinolytic activity was primarily enhanced in patients with AT, who typically present with reduced levels of plasminogen and increased levels of D-dimer (50).…”

“…A study by Ridker et al (54) found that the presence of D-dimers was closely associated with ischemic cardiomyopathy. The elevated levels of D-dimers indicate an increased risk of MI, however, D-dimer was not an independent predictor (49). Previous studies have suggested that the activation of blood coagulation was an independent risk factor of cerebral infarction, where the D-dimer level and the degree of cerebral infarction were linearly correlated, and could be used to infer the prognosis of patients with cerebral infarction (55,56).…”

Elevated plasma D-dimer level is associated with short-term poor outcome in patients with acute ischemic stroke: a prospective, observational study

“…The available investigations of stroke have shown a correlation between D-dimer levels and functional outcomes and the prognostic value of D-Dimer in several different types of population with AIS [35][36][37][38][39]. Nam et al [35] and Nezu et al [36] found a predictive role of D-dimer only in patients with cryptogenic stroke.…”