Arteriopathy, D-Dimer, and Risk of Poor Neurologic Outcome in Childhood-Onset Arterial Ischemic Stroke

Division of Hematology, Departments of Pediatrics and Medicine, Johns Hopkins School of Medicine, Baltimore, MD
The Journal of pediatrics (Impact Factor: 3.79). 12/2012; 162(5). DOI: 10.1016/j.jpeds.2012.11.035
Source: PubMed


To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS).

Study design:
Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Children's Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected.

Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02).

Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

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    ABSTRACT: High-level plasma D-dimer suggests hypercoagulable states. There is a lack of correlation study of plasma D-dimer level and prognosis according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. The goal of this study is to explore the relationship between the plasma D-dimer level and the outcome of acute ischemic stroke patients among different stroke subtypes. We conducted a study of acute ischemic stroke patients admitted to the Department of Neurology in Second Hospital of Lanzhou University within 7 days of symptom onset. They were divided into different groups based on their subtypes according to TOAST criteria. In all the patients the plasma D-dimer levels were detected within 24 h of admission. Clinical neurological assessments were performed in line with National Institutes of Health Stroke Scale (NIHSS) once daily on the day of admission and on the 14th day. The outcome was evaluated by neurological improvement rate. Comparisons were made among the different subtypes based on the level of plasma D-dimer and the outcome. A total of 300 patients with acute ischemic stroke were included, 40 with cardioembolism; 47 with large-artery atherosclerosis; 143 with small-artery occlusion, 5 with other etiology stroke; and 65 with undetermined etiology stroke. The level of plasma D-dimer was negatively related to the outcome (r = -0.41; P = 0.013). Patients with cardioembolism had the highest level of plasma D-dimer and they suffered the most serious neurological deficit and the worst outcome among the five subtypes, the difference was statistically significant (F = 5.34; P = 0.012); while the lacunar stroke patients had the best outcome with the lowest level of D-dimer. High-level plasma D-dimer of acute period strongly indicates an unfavorable clinical outcome.
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    ABSTRACT: It has been suggested that modestly elevated circulating D-dimer values may be associated with acute ischemic stroke (AIS). Thus, the purpose of this study was to investigate the association between plasma D -dimer level at admission and AIS in Chinese population. In a prospective observational study, plasma D-dimer levels were measured using a particle-enhanced, immunoturbidimetric assay on admission in 240 Chinese patients with AIS. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to D-dimer levels. Plasma median D-dimer levels were significantly (P = 0.000) higher in AIS patients as compared to healthy controls (0.88; interquartiler range [IQR], 0.28-2.11 mg/L and 0.31; IQR, 0.17-0.74 mg/L). D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score(r = 0.179, p = 0.005) and infarct volume(r = 0.425, p = 0.000). Those positive trends still existed even after correcting for possible confounding factors (P = 0.012, 0.000; respectively). Based on the Receiver operating characteristic (ROC) curve, the optimal cut-off value of plasma D-dimer levels as an indicator for diagnosis of cardioembolic strokes was projected to be 0.91 mg/L, which yielded a sensitivity of 83.7% and a specificity of 81.5%, the area under the curve was 0.862(95% confidence interval [CI], 0.811-0.912). We had shown that plasma D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score and infarct volume. These associations were independent other possible variables. In addition, cardioembolic strokes can be distinguished from other stroke etiologies by measuring plasma D-dimer levels very early (0-48hours from stroke symptom onset).
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    ABSTRACT: Haemostatic biomarkers associated with poor outcome in acute ischemic stroke (AIS). The objective of the study was to evaluate the predictive value of plasma D-dimer (D-D) on functional outcome at 90-day follow-up from stroke onset. We conducted a prospective, observational cohort study in the emergency department and enrolled 220 patients with AIS. Plasma D-D concentrations, determined by a particle-enhanced, immunoturbidimetric assay, were measured. Each patient's medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. There was a positive correlation between levels of D-D and the NIHSS (r = 0.361, p<0.001), and the infarct volume (r = 0.449, p<0.001). In the 69 patients with an unfavorable functional outcome, D-D levels were higher compared with those in patients with a favorable outcome [3.24(IQR, 2.18-4.60)mg/L vs 0.88(IQR, 0.35-1.77) mg/L; p<0.001]. After adjusting for all other significant outcome predictors, D-D level remained an independent predictor for unfavorable functional outcome and mortality with an odds ratio of 2.18 (95% CI, 1.55-2.83), 3.22 (95% CI, 2.05-6.43); respectively. D-D levels are a useful tool to predict outcome and mortality 90-day after acute ischemic stroke and have a potential to assist clinicians.
    Full-text · Article · Feb 2014 · PLoS ONE
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