Article

Relationship between Plasma D-Dimer Level and Cerebral Infarction Volume in Patients with Nonvalvular Atrial Fibrillation

February 2013
Cerebrovascular Diseases 35(1):64-72

February 2013
35(1):64-72

DOI:10.1159/000345336

Source
PubMed

Authors:

Mari Matsumoto

Osaka University

Shuhei Okazaki

Osaka National Hospital

Shigetaka Furukado

Osaka University

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Background: Plasma D-dimer level may reflect the activity of thrombus formation in the left atrium of patients with nonvalvular atrial fibrillation (NVAF). Proper anticoagulation with warfarin dramatically decreases the rate of cerebral embolism, reduces stroke severity and subsequent risk of death, as well as the level of D-dimer in NVAF patients. However, the predictive value of D-dimer level on cerebral embolism severity has not been examined. Thus, the purpose of this study was to investigate the association between plasma D-dimer level at admission and infarct size in NVAF patients. Methods: We identified 124 patients with consecutive ischemic stroke and NVAF who were admitted within 48 h of symptom onset. We measured infarction volume from CT taken after 3 ± 1 days from the onset. Plasma D-dimer levels were measured at the time of admission. Relationships were analyzed between infarction volume and plasma D-dimer levels, cardiovascular risk factors, preadmission medications and admission conditions. We also assessed the influence of D-dimer level on functional outcome in patients with preadmission modified Rankin Scale (mRS) score of 0-1 and patients by tertile of D-dimer level (≤0.83, 0.83-2.16 and ≥2.16 µg/ml). Results: Infarction volume significantly correlated with D-dimer level (r = 0.309, p < 0.001), systolic blood pressure (r = 0.201, p = 0.026), diastolic blood pressure (r = 0.283, p = 0.002), National Institutes of Health Stroke Scale (NIHSS) score on admission (r = 0.546, p < 0.001) and mRS score at discharge (r = 0.557, p < 0.001). Multivariate regression analyses showed that the D-dimer level was significantly associated with infarction volume after adjusting for age, sex, current smoker or not, prothrombin time-international normalized ratio ≥1.6, diastolic blood pressure, CHADS(2) score and NIHSS score on admission. In patients with a preadmission mRS score of 0-1 (n = 108), D-dimer level was significantly associated with NIHSS score at admission (r = 0.318, p < 0.001) and mRS score at discharge (r = 0.310, p = 0.001). Patients in the highest D-dimer tertile group showed worse outcome than those in the middle (p = 0.041) and lowest (p < 0.001) tertiles. Conclusions: Plasma D-dimer level on admission is significantly related to infarction volume and functional outcome, following cardioembolic stroke in NVAF patients.

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

Preprint

Full-text available

Apr 2019

Background Elevated level of D-dimer increases the risk of ischemic stroke, stroke severity and progression of stroke status, but the association between D-dimer and functional outcome is unclear. The aim of this study is to investigate whether Plasma D-dimer level is a determinant of short-term poor functional outcomes in patients with acute ischemic stroke (AIS). Methods This prospective study included 877 patients with AIS provided plasma D-dimer level after stroke onset. Patients were categorized per D-dimer level: Quartile 1(≤0.24 mg /L), Quartile 2 (0.25–0.56 mg /L), Quartile 3 (0.57–1.78 mg /L), and Quartile 4 (>1.78mg /L). Each patient’s medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale (mRS). Results Of 877 patients were included (mean age, 64 years; male, 68.5%), poor outcome was present in 302 (34.4%) patients. After adjustment for potential confounding variables, higher D-dimer level on admission was associated with poor outcome (adjusted odds ratio [aOR] 2.257, 95% CI1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a D-dimer level ≥0.315 mg/L for pour outcome [area under the ROC curve (AUC) 0.657; sensitivity 83.8%; specificity 41.4%]. Conclusion Elevated plasma D-dimer level on admission was significantly associated with increased poor outcome after admission for AIS, suggesting the potential role of D-dimer as a predictive marker for short-term poor outcomes in patients with AIS.

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

Preprint

Full-text available

Jul 2019

Background: Elevated levels of plasma D-dimer increase the risk of ischemic stroke, stroke severity, and the progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). Methods: This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 h of symptom onset. Patients were categorized by plasma D-dimer level: Quartile 1(≤0.24 mg/L), Quartile 2 (0.25–0.56 mg/L), Quartile 3 (0.57–1.78 mg/L), and Quartile 4 (>1.78 mg/L). The medical record of each patient was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale. Results: Poor outcome was present in 302 (34.4%) of the 877 patients that were included in the study (mean age, 64 years; male, 68.5%). After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio 2.257, 95% confidence interval 1.349–3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor for poor outcome was a plasma D-dimer level ≥0.315 mg/L (area under the ROC curve 0.657; sensitivity 83.8%; specificity 41.4%). Conclusion: Elevated plasma D-dimer levels on admission are significantly associated with poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer level as a predictive marker for short-term poor outcome in patients with AIS.

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

Preprint

Full-text available

Jun 2019

Background: Elevated level of plasma D-dimer increases the risk of ischemic stroke, stroke severity and progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether Plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). Methods: This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 hours of symptom onset. Patients were categorized per plasma D-dimer level: Quartile 1(0.24 mg /L), Quartile 2 (0.25–0.56 mg /L), Quartile 3 (0.57–1.78 mg /L), and Quartile 4 (1.78mg /L). Each patient’s medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale (mRS). Results: Of 877 patients were included (mean age, 64 years; male, 68.5%), poor outcome was present in 302 (34.4%) patients. After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio [aOR] 2.257, 95% CI1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a plasma D-dimer level 0.315 mg/L for pour outcome [area under the ROC curve (AUC) 0.657; sensitivity 83.8%; specificity 41.4%]. Conclusion: Elevated plasma D-dimer level on admission was significantly associated with increased poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer as a predictive marker for short-term poor outcome in patients with AIS.

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

Preprint

Full-text available

May 2019

Prognostic Hemostasis Biomarkers in Acute Ischemic Stroke: A Systematic Review

Article

Full-text available

Jan 2019

Objectives— The prediction of patients at risk for poor clinical outcome after acute ischemic stroke remains challenging. An imbalance of coagulation factors may play an important role in progression and prognosis of these patients. In this systematic review, we assessed the current literature on hemostasis biomarkers and the association with poor clinical outcome in acute ischemic stroke. Approach and Results— A systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar was performed on studies reporting on hemostasis biomarkers and clinical outcome after acute ischemic stroke. Studies were considered eligible if blood samples were collected within 72 hours after symptom onset. Additionally, clinical outcome should be assessed using a disability score (Barthel Index or modified Rankin scale). Methodological quality of included studies was assessed with an adapted version of the Quality Assessment of Diagnostic Accuracy Studies questionnaire. A total of 80 articles were read full text, and 41 studies were considered eligible for inclusion, reporting on 37 different hemostasis biomarkers. No single biomarker appeared to be effective in predicting poor clinical outcome in acute ischemic stroke patients. Conclusions— Based on current literature, no clear recommendations can be provided on which hemostasis biomarkers are a predictor of clinical outcome after acute ischemic stroke. However, some biomarkers show promising results and need to be further investigated and validated in large populations with clear defined study designs.

D-dimer Level is Correlated with Prognosis, Infarct Size, and NIHSS in Acute Ischemic Stroke Patients

Article

Full-text available

Jan 2021

Stroke ranks the fourth leading disease causing adult mortality and disability. D-dimer (D-D) is the ultimate product of plasmin-mediated degradation of fibrin-rich thrombi. D-D is a simple readily accessible biomarker employed within the diagnostic algorithms for the exclusion of venous thromboembolism. The correlation between D-D infarct size in MRI brain, APACHE II score, and the National Institute of Health Stroke Scale (NIHSS) score in critically ill acute stroke patients has not been fully investigated before. Objective: We aimed to investigate the diagnostic and prognostic value of elevated plasma D-D in critically ill patients admitted with acute cerebrovascular accidents. As far as we know, we are the first to investigate the correlation between plasma D-D levels and the ischemic lesion size in MRI brain and also APACHE II score and NIHSS in critically ill acute ischemic cerebrovascular patients. Setting and participants: A prospective, observational cohort study inside the Critical Care Medicine Department. Thirty patients with AIS were enrolled additionally to 1 healthy age- and sex-matched controls. Interventions: We employed particle-enhanced, immunoturbidimetric assay to detect plasma D-D concentrations. D-D levels D0 and D1 were measured upon admission and 24 hours later, respectively. We reviewed the patient' s health records; additionally, demographic, clinical, laboratory, and neuroimaging information was abstracted. Results: D-D concentrations were significantly higher in acute stroke patients compared to healthy controls. ROC curve analysis showed that elevated D-D level more than 310 ng/mL can predict infarct lesion size >1.5 cm in diffusion-weighted MRI brain with sensitivity and specificity (100 and 83%, respectively) and also admission D-D (D0) at cutoff concentration 350 ng/mL and D1 at cutoff value 370 ng/mL are predictors of complicated course with sensitivity and specificity (100 and 84.6%, respectively). There was no significant difference between D0 and D1 D-D levels (p-value >0.05). Conclusion: The plasma D-D biomarker can be a simple readily available test reliable predictor of infarct lesion size >1.5 cm in DW-MRI and outcome in union with the common practice instrumental tests. How to cite this article: Abbas NI, Sayed O, Samir S, Abeed N. D-dimer Level is Correlated with Prognosis, Infarct Size, and NIHSS in Acute Ischemic Stroke Patients. Indian J Crit Care Med 2021;25(2):193-198.

D-dimer level elevation can aid in detection of asymptomatic COVID-19 presenting with acute cerebral infarction

Article

Full-text available

Mar 2021

Coronavirus disease 2019 (COVID-19) mainly manifests as a respiratory syndrome, besides causing other complications. Severe COVID-19 may also present with coagulopathy, leading to venous thrombosis and cerebral infarction. Generally, acute stroke is a secondary complication in patients displaying respiratory syndromes. Here, we present a case of acute stroke in an 84-year-old female patient who did not manifest any respiratory symptoms. The patient had no cough or fever before the stroke onset; nevertheless, COVID-19 PCR test was positive. The patient also had markedly elevated serum D-dimer levels. Our findings suggest that coagulopathy can occur even in a patient with asymptomatic COVID-19 infection, and to our knowledge, this is the first report of such a case. We concluded that elevated D-dimer levels can serve as an additional COVID-19 screening tool in stroke patients.

-NC-ND license D-dimer level elevation can aid in detection of asymptomatic COVID-19 presenting with acute cerebral infarction

Article

Full-text available

Jan 2021

D-dimer level and outcome of minor ischemic stroke with large vessel occlusion

Article

Mar 2020
J NEUROL SCI

Objective To determine the predictors of unfavorable outcomes in acute minor ischemic stroke patients with large vessel occlusion. Methods The derivation cohort included ischemic stroke patients admitted to a comprehensive stroke center within 7 days after onset with large vessel occlusion and an initial National Institutes of Health Stroke Scale score of 5 or less. An unfavorable outcome was defined as dependency (modified Rankin Scale score of 3 to 6) at 3 months from the onset. The predictive values of factors related to an unfavorable outcome were evaluated. External validation was performed from a stroke registry of a tertiary medical center. Results In the derivation cohort, 3839 consecutive patients were screened; a total of 130 patients were included. Twenty-four (18%) patients had unfavorable outcomes. In multivariate analysis, D-dimer ≥1900 μg/l (odds ratio (OR) 3.31, 95% confidence interval (CI) 1.14–9.61, p = .028) and age (OR 2.01, 95% CI 1.05–3.86, p = .035) were independently associated with an unfavorable outcome. No significant differences were observed regarding occluded vessel sites. In the validation cohort, 850 consecutive patients were screened; a total of 74 patients were included. D-dimer ≥1900 μg/l (OR 8.78, 95% CI 1.41–54.61, p = .020) was the only factor independently associated with an unfavorable outcome, as in the derivation cohort. Conclusions A high D-dimer level on admission could help predict unfavorable outcomes in patients with a minor ischemic stroke with large vessel occlusion.

Elevated plasma D-dimer levels are associated with short-term poor outcome in patients with acute ischemic stroke: A prospective, observational study

Article

Full-text available

Jul 2019
BMC NEUROL

Background: Elevated levels of plasma D-dimer increase the risk of ischemic stroke, stroke severity, and the progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). Methods: This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 h of symptom onset. Patients were categorized by plasma D-dimer level: Quartile 1(≤0.24 mg/L), Quartile 2 (0.25-0.56 mg/L), Quartile 3 (0.57-1.78 mg/L), and Quartile 4 (> 1.78 mg/L). The medical record of each patient was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale. Results: Poor outcome was present in 302 (34.4%) of the 877 patients that were included in the study (mean age, 64 years; male, 68.5%). After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio 2.257, 95% confidence interval 1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor for poor outcome was a plasma D-dimer level ≥ 0.315 mg/L (area under the ROC curve 0.657; sensitivity 83.8%; specificity 41.4%). Conclusion: Elevated plasma D-dimer levels on admission are significantly associated with poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer level as a predictive marker for short-term poor outcome in patients with AIS.

The Association between Coagulation and Atrial Fibrillation

Article

Full-text available

Jan 2024

The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and newly diagnosed cases of atrial fibrillation (AF). However, this article summarizes the role of coagulation in the pathogenesis of AF, which includes fibrinogen and fibrin, prothrombin, thrombomodulin, soluble urokinase plasminogen activator receptor, von Willebrand factor, P-selectin, D-dimer, plasminogen activator inhibitor-1, and platelet activation. Coagulation irregularities play a significant role in the pathogenesis of AF.

Prognostic Determinants of Anterior Large Vessel Occlusion in Acute Stroke in Elderly Patients

Article

Full-text available

Jan 2024

This study investigated prognostic factors in elderly patients (80 years and older) undergoing mechanical thrombectomy (MT) for anterior circulation large vessel occlusion (LVO) in acute stroke treatment. Of 59 cases, 47.5% achieved a favorable outcome (mRS ≤ 3) at three months, with a mortality rate of 20.3%. Factors associated with better outcomes included younger age, lower admission National Institute of Health Stroke Scale (NIHSS) scores, lower N-terminal pro-brain natriuretic peptide (NT-proBNP) and D-dimer levels, the presence of the first pass effect (FPE), and successful recanalization. However, logistic regression showed that only lower admission NIHSS scores were significantly correlated with favorable outcomes. In addition, this study suggests that lower admission NT-proBNP and D-dimer levels could potentially serve as prognostic indicators for elderly LVO patients undergoing MT.

Preprocedural D-Dimer Level as a Predictor of First-Pass Recanalization and Functional Outcome in Endovascular Treatment of Acute Ischemic Stroke

Article

Full-text available

Sep 2023

We aimed to evaluate the association between preprocedural D-dimer levels and endovascular and clinical outcomes. We retrospectively reviewed patients with acute intracranial large-vessel occlusion who underwent mechanical thrombectomy. Plasma D-dimer levels were measured immediately before the endovascular procedure. Endovascular outcomes included successful recanalization, first-pass recanalization (first-pass effect (FPE) and modified FPE (mFPE)), thrombus fragmentation, and the number of passes of the thrombectomy device. Clinical outcomes were assessed at 3 months using the modified Rankin Scale. A total of 215 patients were included. Preprocedural D-dimer levels were lower in patients with FPE (606.0 ng/mL [interquartile range, 268.0–1062.0]) than in those without (879.0 ng/mL [437.0–2748.0]; p = 0.002). Preprocedural D-dimer level was the only factor affecting FPE (odds ratio, 0.92 [95% confidence interval, 0.85–0.98] per 500 ng/mL; p = 0.022). D-dimer levels did not differ significantly based on successful recanalization and thrombus fragmentation. The number of passes of the thrombectomy device was higher (p = 0.002 for trend) and the puncture-to-recanalization time was longer (p = 0.044 for trend) as the D-dimer levels increased. Patients with favorable outcome had significantly lower D-dimer levels (495.0 ng/mL [290.0–856.0]) than those without (1189.0 ng/mL [526.0–3208.0]; p < 0.001). Preprocedural D-dimer level was an independent factor for favorable outcome (adjusted odds ratio, 0.88 [0.81–0.97] per 500 ng/mL; p = 0.008). In conclusion, higher preprocedural D-dimer levels were significantly associated with poor endovascular and unfavorable functional outcomes.

Clinical features of ischemic stroke in patients with nonvalvular atrial fibrillation combined with intracranial atherosclerotic stenosis

Article

Full-text available

May 2023

Background Nonvalvular atrial fibrillation (NVAF) and intracranial atherosclerotic stenosis (ICAS) are major causes of ischemic stroke. Relatively few studies have focused on the risk factors and clinical features of ischemic stroke caused by NVAF combined with ICAS. Method We retrospectively evaluated NVAF and/or ICAS in patients with acute ischemic stroke admitted within 72 h after stroke. All patients with acute ischemic stroke underwent diffusion‐weighted magnetic resonance imaging (DWI), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and/or digital subtraction angiography (DSA). NVAF was detected by routine electrocardiogram or 24‐h Holter examination, Doppler echocardiography, and contrast echocardiography of the right heart. Results Among the 635 enrolled patients, NVAF, ICAS, and NVAF+ICAS were diagnosed in 170 (26.77%), 255 (40.16%), and 210 (33.07%) patients, respectively. Patients in the NVAF+ICAS group were older (p < .001), specifically aged ≥75 years (p < .001). The admission time of the NVAF+ICAS group was shorter (p < .001) than that of the ICAS group. The admission NIHSS score of the NVAF group was higher than that of the NVAF+ICAS group (p < .001). HsCRP, NTpro‐BNP, and LEVF levels were significantly different among the three groups (p < .001). NVAF+ICAS ischemic stroke occurred mainly in the right hemisphere (52.4%). Conclusion NVAF with ICAS ischemic stroke is more likely to occur in older patients. Infarctions occurred mainly in the right cerebral hemisphere. Neurological deficits in NVAF are more severe than those in NVAF combined with ICAS and in simple ICAS ischemic strokes. HsCRP, LEVF, andNTpro‐BNP seem to be closely associated with NVAF+ICAS ischemic stroke.

Prevalence of deep vein thrombosis in patients with stroke in the first three days of hospitalization

Article

Dec 2022

Introduction. Sonography of lower extremity veins is advised to be used for evaluation VTE in patients with stroke, however, the timing of the evaluation remains uncertain, therefore the prevalence of VTE and associated factors in different time intervals of hospitalization is necessary to be studied. Aim – to investigate the prevalence of lower extremity veins thrombosis by sonography compared with the prevalence of associated factors (D-dimer level in the blood, the risk of VTE by Padua score system) in patients with stroke in the first 3 days of hospitalization. Materials and methods. The study enroled 50 patients hospitalized in the Botkin State Clinical Hospital of Moscow with stroke. Sonography of lower extremity veins was performed, the level of D-dimer in the blood was determined, the risk of VTE by Padua score system was assessed in the first 3 days of hospitalization. The prevalence of these indicators has been studied. Results. Increased D-dimer level was detected in the majority of patients: 84 % of all patients (42 of 50), 85 % of patients with ischemic stroke (34 of 40), 78 % with hemorrhagic stroke (7 of 9) and in a single patient with TIA. 30 % of all patients (15 of 50), 32.5 % of patients with ischemic stroke (13 of 40), 22 % of patients with hemorrhagic stroke (2 of 9) had high risk of VTE according to Padua (≥ 4 points). The prevalence of lower extremity veins thrombosis according the sonography results was 6 % (3 of 50), that is 14 times less than the prevalence of increased D-dimer level and 5 times less than the prevalence of high risk of VTE by Padua score system. About 66 % of mpatients having thrombosis (2 of 3) were suffering from active cancer. Conclusion. Patients with stroke in the first 3 days of hospitalization has significant prevalence of lower extremity deep vein thrombosis according to sonography, but factors that distinguish these patients need to be clarified. Lower prevalence of increased D-dimer level and the high risk of VTE by Padua in post-stroke patients during this period of hospitalization seem to be doubtful criteria compared with prevalence of lower extremity deep vein thrombosis for selection to sonography. The distinguishing risk factor for VTE by Padua in 66 % of patients with evaluated deep vein thrombosis in the first 3 days of hospitalization with stroke was an active cancer.

Atrial fibrillation and stroke

Article

Full-text available

Dec 2022
Expet Rev Cardiovasc Ther

Introduction: : Stroke is one of the leading causes of mortality and morbidity globally. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is set to reach epidemic proportions. AF is associated with a five-fold increase in risk of stroke. Strokes caused by AF more often are fatal or result in severe disability. Even though the incidence of stroke has been significantly reduced by oral anticoagulation, AF is thought to account for a significant proportion of cryptogenic strokes where no aetiology is identified. Areas covered: : This article reviews the literature related to AF and stroke, pathophysiological insights, diagnosis of AF in stroke patients, and its management (graphical abstract). Expert opinion: : The pathophysiology of thrombogenesis that links AF and stroke is not well understood and is an area of active research to identify new therapeutic targets to prevent AF and stroke. As the nature of AF and stroke is multifaceted, an integrated care approach to managing AF and stroke is increasingly essential.

Correlation Between Serum Albumin and D-Dimer Levels in 909 Patients with Non-Valvular Atrial Fibrillation: A Retrospective Study from a Single Center in China

Article

Full-text available

Nov 2022
MED SCI MONITOR

Background D-dimer level can reflect the hypercoagulable state of atrial fibrillation (AF) and predict thromboembolic events. However, no effective indicator associated with D-dimer of AF patients has been found to prevent thromboembolic events in AF. This retrospective study from a single center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm. Material/Methods A total of 909 NVAF patients and 653 sex- and age-matched sinus rhythm participants were used to compare serum albumin and D-dimer levels. Serum albumin was determined by colorimetry, and D-dimer level was determined by latex-enhanced photoimmunoassay. We analyzed the correlation of serum albumin and D-dimer with NVAF by correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve. Results Albumin (P<0.001) and D-dimer (P<0.001) were significantly associated with NVAF. Among NVAF patients, D-dimer level was negatively correlated with albumin levels (P<0.001), and albumin level was an independent risk factor of abnormal D-dimer level (>0.5 ug/mL), which was also an effective predictor of abnormal D-dimer level (the area under the ROC curve was 0.77, P<0.001), and the optimal cutoff value was 36.95 g/L. Conclusions Serum albumin and D-dimer levels were significantly associated with NVAF. In NVAF patients, D-dimer level was inversely correlated with albumin levels, and albumin level was an independent risk factor and effective predictor of abnormal D-dimer level. Close examination and supplementation of serum albumin can prevent thromboembolic events, but further clinical research and confirmation are needed.

Clinical Application of Thromboelastography in Acute Ischemic Stroke

Article

Full-text available

Oct 2022
CLIN APPL THROMB-HEM

Acute ischemic stroke (AIS), characterized by high morbidity and mortality, has imposed a considerable burden on society. Despite rapid development in the treatment of AIS, there is still a high risk of recurrence. Furthermore, there is a time delay in waiting for the results of conventional coagulation tests in candidate patients for intravenous thrombolysis therapy. Heterogeneous responses to antiplatelet, intravascular thrombolysis, and endovascular therapies also worsen the situation. Thromboelastography (TEG), as a global and portable detection method for hemostasis, facilitates clinicians in disease monitoring, treatment evaluation, and prognosis prediction in AIS. In this narrative review, we provided a comprehensive summary of the clinical application of TEG in ischemic stroke and gave insights to further studies.

Increased plasma D-dimer levels may be a promising indicator for diabetic peripheral neuropathy in type 2 diabetes

Article

Full-text available

Aug 2022

Background Increased plasma D-dimer levels have been reported to be associated with a range of adverse health outcomes. This study aimed to determine whether plasma D-dimer is connected to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods This study was part of a series exploring the potential risks for DPN. All patients were questioned for neurologic symptoms, examined for neurologic signs, and received nerve conduction studies to collect nerve action potential onset latency, amplitude, and nerve conduction velocity (NCV). Composite Z scores of latency, amplitude, and NCV were calculated. DPN was confirmed as both at least a neurologic symptom/sign and an abnormality of nerve conduction studies. Coagulation function indices, such as plasma D-dimer levels, were also synchronously detected. Results We finally recruited 393 eligible patients for this study, of whom 24.7% ( n = 97) were determined to have DPN. The plasma D-dimer level was found to be closely associated with the composite Z score of latency, amplitude, and NCV after adjusting for other coagulation function indices and clinical covariates (latency: β = 0.134, t = 2.299, p = 0.022; amplitude: β = –0.138, t = –2.286, p = 0.023; NCV: β = –0.139, t = –2.433, p = 0.016). Moreover, the prevalence of DPN in the first, second, third, and fourth quartiles (Q1, Q2, Q3, and Q4) of the D-dimer level was 15.2%, 15.9%, 26.4%, and 42.7%, respectively ( p for trend < 0.001). The corresponding adjusted odds ratios and 95% CIs for DPN in D-dimer quartiles were 1, 0.79 (0.21–2.99), 1.75 (0.49–6.26), and 5.17 (1.38–19.42), respectively. Furthermore, the optimal cutoff value of the plasma D-dimer level to discriminate DPN was ≥0.22 mg/L (sensitivity = 67.01%, specificity = 58.78%, and Youden index = 0.26) after analysis by the receiver operating characteristic curve. Conclusions Increased plasma D-dimer levels may be a promising indicator for DPN in patients with T2D.

Relationship between D-dimer levels and infarct pattern in acute ischemic stroke patients with non-valvular atrial fibrillation

Article

Jun 2022

Background: Cerebral embolism in patients with non-valvular atrial fibrillation (NVAF) is mainly caused by thrombus formation in the left atrial appendage. D-dimer is known to reflect the thrombogenic activity of the left atrium in NVAF patients. This study aimed to investigate the relationship between D-dimer levels and infarct pattern in ischemic stroke patients with NVAF. Methods: We enrolled 255 patients who developed cardioembolic stroke caused by NVAF and presented to the hospital within 7 days. We divided the infarct pattern into two groups: single lesions (SL) and multiple lesions (ML). The infarct pattern was also classified into two groups: ischemic lesions involving a single vascular territory (ST) and multiple vascular territories (MT). We analyzed the relationship between the infarct pattern and D-dimer levels. Results: Of the 255 patients, 79 (31.0%) and 176 (69.0%) were in the SL and ML groups, respectively. In addition, 207 (81.2%) and 48 (18.8%) patients were classified into the ST and MT groups, respectively. Compared with the SL group, a higher D-dimer level was observed in the ML group (p=0.006). Similarly, the MT group had higher D-dimer levels than the ST group (p=0.001). Logistic regression analysis showed that elevated D-dimer levels were significantly and independently associated with the presence of multiple ischemic lesions (p=0.021) and the involvement of multiple vascular territories (p=0.020). Conclusions: This study showed that elevated D-dimer levels were independently associated with multiple ischemic lesions involving multiple vascular territories in ischemic stroke patients with NVAF.

Role of D-Dimer in Stroke: A Systematic Review

Article

Full-text available

Jan 2022

ROLE OF SERUM D DIMER LEVELS IN ACUTE ISCHEMIC STROKE

Article

Full-text available

Dec 2021

Background: Acute ischemic stroke has been known to be a severely debilitating affliction with a steep disability and co morbidity curve. Various tools and methods have been attempted to ascertain if the diagnosis and prognosis of stroke can be achieved faster as it aids in effective management as well as reduces the resultant damage to the brain. Aim: The present study was designed to assess if serum D Dimer levels can be used as a marker as well as a volumetric determinant of stroke. Methods: The study involved a patient pool of 50 patients and corresponding controls who were matched for age and gender. The data collected included demographic data, baseline clinical parameters, serum D Dimer levels and a radiological assessment of the volume of infract. Findings: The study revealed that a relationship exists between the levels of circulating D Dimer and DW MRI weighted images showing infarcts. The relationship was direct in nature. Conclusion: D Dimer levels can provide a estimate of the area under infarction and thus prove to be a prognostic as well as diagnostic marker. Keywords: Acute ischaemic Stroke, D Dimer, Volumetric Association

Level of fibrinogen, D-dimers and C-reactive protein, and correlations between these parameters in ischemic and haemorrhagic stroke

Article

Full-text available

Oct 2021

Introduction and objective Fibrinogen (FIB) and C-reactive protein (CRP) play an important role in any inflammatory response. FIB levels may be higher in stroke patients compared to non-stroke patients. CRP is used to detect inflammation due to its high sensitivity in aseptic inflammation. Blood levels of d-dimer (DD) are used to determine the amount of fibrin formed and distributed. Inflammation may play an important role in the pathogenesis of haemorrhagic stroke causing primal da-mage, and in ischemic stroke causing secondary damage due to a decrease in perfusion in the brain. The aim of the study is to prove the hypothesis that the inflammatory process is involved in the pathogenesis of ischemic and haemorrhagic stroke. Material and methods The study used data from a retrospective study conducted on a group of 402 stroke patients, among which the levels of FIB, CRP and DD were compared. The patients were hospitalized in the Department of Neurology of the Medical University (MU) in Białystok from 1 January – 31 December 2016. Patients’ data was obtained from medical records. The diagnosis of stroke was confirmed by CT of the head. Patients with other brain injuries were excluded from the study. The study was approved by the Bioethics Committee of the MU of Bialystok. The applied research method was the statistical method. Results A positive moderate correlation was found between CRP and FIB. In the group of patients with ischemic stroke it was higher (0.59) than in the group of patients with haemorrhagic stroke(0.22). Moreover, in the group of patients with ischemic stroke, a correlation was found between DD and CRP(0.517). Conclusions Inflammatory process is involved in pathogenesis of ischemic and haemorrhagic stroke, but could be associated with comorbid diseases. Increased CRP correlates with higher levels of FIB and DD in the ischemic stroke but not in the haemorrhagic stroke.

Difference in left atrial D-dimer level in patients with atrial fibrillation treated with direct oral anticoagulant

Article

Full-text available

Oct 2021
BMC Cardiovasc Disord

Background Atrial fibrillation (AF) may cause cerebral and systemic embolism. An increased D-dimer level indicates hyperactivation of secondary fibrinolysis, resulting in predilection for thrombosis. To clarify the differential effects of anticoagulation therapy, we compared the D-dimer levels in peripheral and left atrial (LA) blood of atrial fibrillation patients scheduled for ablation. Methods We analyzed 141 patients with non-valvular AF (dabigatran, n = 30; apixaban, n = 47; edoxaban, n = 64; mean age: 68 years, male: 60%). Peripheral venous blood and LA blood was collected before pulmonary vein isolation. We examined the laboratory and echocardiographic parameters. Results After adjusting for baseline characteristics, D-dimer level in the LA was significantly higher in patients treated with edoxaban than that in those on apixaban (0.77 ± 0.05 vs. 0.60 ± 0.05 μg/mL, P = 0.047), although there were no significant differences in peripheral D-dimer levels. We classified the D-dimer value of the LA into a normal group (< 0.9) and a high value group (≥ 1.0); the peripheral prothrombin fragment F1 + 2 level (odds ratio [OR] 1.012; 95% confidence interval [CI]: 1.003–1.022; P = 0.008) and left ventricular ejection fraction (LVEF) (OR, 0.947; 95% CI, 0.910–0.986; P = 0.008) were potential predictors of high LA D-dimer levels. Conclusions In apixaban-treated patients, the D-dimer level in the left atrium was lower than in edoxaban-treated patients on the day of ablation, suggesting that the anticoagulant effect of apixaban on the left atrium is better than that of edoxaban in patients with AF.

RELATIONSHIP BETWEEN SERUM D DIMER LEVELS WITH QUANTIFICATION OF ACUTE ISCHEMIC STROKE

Article

Full-text available

Aug 2021

Background: Acute ischemic stroke has been known to be a severely debilitating affliction with a steep disability and co-morbidity curve. Various tools and methods have been attempted to ascertain if the diagnosis and prognosis of stroke can be achieved faster as it aids in effective management as well as reduces the resultant damage to the brain. Aim: The present study was designed to assess if serum D Dimer levels can be used as a marker as well as a volumetric determinant of stroke. Methods: The study involved a patient pool of 50 patients and corresponding controls who were matched for age and gender. The data collected included demographic data, baseline clinical parameters, serum D Dimer levels and a radiological assessment of the volume of infract. Findings: The study revealed that a relationship exists between the levels of circulating D Dimer and DW MRI weighted images showing infarcts. The relationship was direct in nature. Conclusion: D Dimer levels can provide a estimate of the area under infarction and thus prove to be a prognostic as well as diagnostic marker. Keywords: Acute ischaemic Stroke, D Dimer, Volumetric Association

Effects of CHADS2 Score, Echocardiographic and Haematologic Parameters on Stroke Severity and Prognosis in Patients with Stroke due to Nonvalvular Atrial Fibrillation

Article

Full-text available

Jul 2019

Background and purpose: The aim of this study is to evaluate utility of CHADS2 score to estimate stroke severity and prognosis in patients with ischemic stroke due to non-valvular atrial fibrillation (AF) in addition to evaluate effects of hematologic and echocardiographic findings on stroke severity and prognosis. Methods: This prospective study included 156 ischemic stroke cases due to non-valvular AF in neurology ward of Trakya University Medical School between March 2013-March 2015. National Institute of Health Stroke (NIHS) score was used to evaluate severity of stroke at admission. Carotid and vertebral Doppler ultrasonography findings, brain computed tomography (CT) and magnetic resonance imaging (MRI) of the cases were evaluated. Left atrial diameter and ejection fraction (EF) values were measured. CHADS2 score was calculated. Modified Rankin Scale was used to rate the degree of dependence. Effects of age and sex of the patients, presence of diabetes mellitus (DM), Congestive Heart Failure (CHF), Cerebrovascular Disease (CVD) and C-reactive protein (CRP) levels on CHADS2, NIHS, and mRS were evaluated. Results: In patients with age ≥75, mean NIHS score was 3.3 points and mean mRS score was 1.02 points higher, than in patient below 75 years of age. Compared with the mild risk group, cases in the high risk group had older age, higher serum D-dimer, fibrinogen and CRP levels and lower EF. A positive relation was detected between stroke severity and Hemorrhagic Transformation (HT), previous CVD history, and presence of CHF. A significant association was found between increased stroke severity and Early Neurological Deterioration (END) development. Older age, higher serum fibrinogen, D-dimer, CRP and lower EF values were associated with poor prognosis. History of CVD and presence of CHF were associated with poor prognosis. END development was found to be associated with poor prognosis. In the high-risk group, 30.3% (n = 33) had END. Among those in the high-risk group according to the CHADS2 score, END development rate was found to be significantly higher than in the moderate risk group (p <0.05). There was a strong positive correlation between CHADS2 and NIHS scores. mRS score increased with increasing CHADS2 score and there was a strong correlation between them. Effect of stroke severity on prognosis was assessed and a positive correlation was found between NIHS score and mRS value. Conclusion: Our study demonstrated the importance of CHADS2 score, haemostatic activation and echocardiographic findings to assess stroke severity and prognosis. Knowing factors which affect stroke severity and prognosis in patients with ischemic stroke may be directive to decide primary prevention and stroke management.

The Link between Early Biomarker Analysis and the Neurological Outcome in Stroke Patients

Article

Jan 2017

New Quick And Easy Publication - Will be edited by Biblio team

Article

Jan 2017

Said Hachimi-Idrissi

Cardiovascular Biomarkers during Acute Periods of Ischemic Stroke due to Non-Valvular Atrial Fibrillation

Article

Full-text available

Jun 2018

Background A subanalysis study of the ENGAGE AF-TIMI 48 trial showed that cardiac troponin I, N-terminal proB-type natriuretic peptide, and D-dimer, were powerful predictors of cerebrovascular adverse events. We aimed to evaluate D-dimer and cardiac troponin I levels during the acute period of ischemic stroke in anticoagulation-naïve patients with non-valvular atrial fibrillation (NVAF) and also studied the association between these biomarkers and stroke severity. Methods Consecutive anticoagulation-naïve patients with acute ischemic stroke due to NVAF were enrolled within two days after each stroke event, and all patients were stratified into either moderate-to-severe or mild neurologic deficit groups using the National Institutes of Health Stroke Scale (NIHSS) at admission. Results A total of 98 patients were enrolled in this study. The median value for the D-dimer was above the upper limit of the normal reference range, but the troponin I value was within the normal range for all patients. After adjusting for CHA2DS2-VASc risk factors, the log-transformed values for D-dimer were positively correlated with an increasing NIHSS score (r=0.233; P=0.051). In the multivariate logistic analysis, the log-transformed D-dimer was positively associated with more severe strokes (odds ratio, 30.1; 95% confidence interval [CI], 1.9-486.2 and 29.7; 95% CI, 2.0-430.8 in the upper two quartiles respectively). The log-transformed values for troponin I did not correlate with the NIHSS score. Conclusion D-dimer levels were higher and an independent risk factor for severe stroke in anticoagulation-naïve patients with NVAF related stroke. In contrast, troponin I levels were normal and were not associated with stroke severity.

Covert atrial fibrillation and atrial high-rate episodes as a potential cause of embolic strokes of undetermined source: Their detection and possible management strategy

Article

Mar 2018
J Cardiol

Cryptogenic ischemic stroke, defined as stroke of undetermined etiology, accounts for 7-25% of all ischemic strokes. Stroke severity is reported to be less severe than cardioembolic stroke and similar to large-artery atherosclerosis. Because its etiology is believed to be mostly an embolic type, it is often called "embolic strokes of undetermined source" (ESUS). In patients with ESUS, it is of significant importance to seek an embolic source with intensive diagnostic assessment, which mostly originates from the heart. Covert atrial fibrillation (AF) and atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices are believed to contribute to the pathogenesis of ESUS. AHRE is common not only in device-implanted patients, but also in older patients with cardiovascular risk factors. However, it is unclear whether AHRE is a direct cause or simply a risk marker of stroke. Furthermore, indication of anticoagulation therapy for stroke prevention in patients with AHRE remains undetermined. In this review, we focus on the roles of covert AF and AHRE in the pathogenesis of cryptogenic ischemic stroke or ESUS. Detection of covert AF and AHRE, and possible management strategies are also discussed.

Impact of D-dimer levels for short-term or long-term outcomes in cryptogenic stroke patients

Article

Full-text available

Mar 2018
J NEUROL

Background: D-dimer levels are used in several clinical settings, such as in predicting venous thrombosis, cardioembolic stroke and cancer status. In the present study, we investigated the associations between plasma D-dimer levels at admission, clinical characteristics and mortality at discharge in cryptogenic stroke patients. We also investigated whether D-dimer levels can predict long-term outcomes in those patients, including those with and without right-to-left shunt (RLS). Methods: Acute cryptogenic stroke patients (n = 295, 72 ± 13 years old) were consecutively enrolled and retrospectively analyzed. We defined the cryptogenic stroke as an undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Plasma D-dimer levels at admission were evaluated. Assessments for RLS were performed using saline contrast-transcranial Doppler ultrasonography or contrast-transesophageal echography. Survivors (at discharge) underwent follow-up for up to 3 years after stroke onset. Results: Of the total enrolled cohort, 17 patients died at discharge. D-dimer levels correlated with initial National Institutes of Health Stroke Scale (NIHSS) score (r = 0.391, P < 0.001) and were associated with mortality at discharge [odds ratio 1.04; 95% confidence interval (CI) 1.00-1.08, P = 0.049] after adjusting for age, sex and initial NIHSS score. Of the 278 survivors at discharge, 266 patients were evaluated to assess RLS during hospitalization, and 62 patients (23.3%) exhibited RLS. According to the median plasma D-dimer levels at admission (0.7 µg/ml), the patients were divided into a low D-dimer group (n = 136, < median) and a high D-dimer group (n = 130, ≥ median). Patients in the high D-dimer group were older, more frequently female, had a lower BMI, had a higher prevalence of cancer and had greater initial neurological severity compared to the patients in the low D-dimer group. During the follow-up period (median, 1093 days), 31 patients developed recurrent stroke and 33 patients died. High D-dimer levels at admission were independently associated with recurrent stroke and all-cause mortality [hazard ratio (HR) 3.76; 95% CI 1.21-14.1, P = 0.021) in patients with RLS, but not in those without RLS (HR 1.35; 95% CI 0.74-2.50, P = 0.335). Conclusions: Increased D-dimer levels at admission were associated with mortality at discharge in cryptogenic stroke patients. In addition, high D-dimer levels were also associated with long-term outcomes in cryptogenic stroke patients with RLS.

Open Access Cardiovascular Pharmacology: Open Access

Article

Full-text available

Oct 2017

Stroke patients have an uncertain prognosis. It has been postulated that biomarkers’ concentrations upon admission could be linked to the neurological outcome. This meta-analysis reviewed the literature and collected data for 65 biomarkers. To increase power of evidence, only biomarkers who were: • Signi cant in the meta-analysis, • Reported by two or more studies conducted by different authors, • Displaying more than 300 patients and • Displaying less or equal to 60% heterogeneity were retained. Eight biomarkers were found to be relevant; TNFα, white blood cell count, non-fasting glucose, GPT, D-dimer, fT3, cortisol and MRproANP. These except for GPT and fT3 show the same trend: a low concentration at admission is linked to a good outcome. For GPT and fT3 the reverse was observed; a low concentration in the acute phase was linked to an adverse outcome. Early biomarker analysis would help the physician to determine the extent of the neurological de cit in stroke patients. This can guide them to implement new treatment strategies such as intensive rehabilitation or a more aggressive treatment.

Brain Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with Atrial Fibrillation

Article

Full-text available

Mar 2017

Background Since stroke patients with nonvalvular atrial fibrillation (NVAF) have poor outcomes in general, the prediction of outcomes following discharge is of utmost concern for these patients. We previously reported that brain natriuretic peptide (BNP) levels were significantly higher in NVAF patients with larger infarcts, higher modified Rankin Scale (mRS) score, and higher CHADS2 score. In the present study, we evaluated an array of variables, including BNP, in order to determine significant predictors for functional outcome in patients with NVAF after acute ischemic stroke (AIS). Methods A total of 615 consecutive patients with AIS within 48 h of symptom onset, admitted to our hospital between April 2010 and October 2015, were retrospectively searched. Among these patients, we enrolled consecutive patients with NVAF. We evaluated the mRS score 3 months after onset of stroke and investigated associations between mRS score and the following clinical and echocardiographic variables. Categorical variables included male sex, current smoking, alcohol intake, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, peripheral artery disease, use of antiplatelet drugs, anticoagulants, or tissue plasminogen activator (tPA), and infarct size. Continuous variables included age, systolic blood pressure (SBP), diastolic blood pressure, hemoglobin, creatinine, D-dimer, brain natriuretic peptide (BNP), left atrial diameter, left ventricular ejection fraction (EF), and early mitral inflow velocity/diastolic mitral annular velocity (E/e’). We also analyzed the association of prestroke CHADS2, CHA2DS2-VASc, and R2CHADS2 scores, and National Institutes of Health Stroke Scale (NIHSS) score on admission with mRS score 3 months after the onset of stroke. Patients were classified into 2 groups according to mRS score: an mRS score ≤2 was defined as good outcome, an mRS score ≥3 was defined as poor outcome. To clarify the correlations between categorical or continuous variables and mRS score, uni- and multivariate logistic regression models using the stepwise variable selection method were applied. Results Among 157 patients with NVAF after AIS, 63.7% were male and the mean age was 75.9 years. In univariate regression analysis, poor outcome (mRS score ≥3) was associated with use of tPA, infarct size, age, SBP, BNP, EF, and NIHSS score. In multivariate regression analysis, BNP levels (odds ratio [OR] 6.40; 95% confidence interval [CI] 1.26–32.43; p = 0.0235) and NIHSS score (OR 2.87; 95% CI 1.84–4.47; p < 0.001) were significantly associated with poor outcome (mRS score ≥3) after adjusting for use of tPA, infarct size, age, BNP, EF, and NIHSS score. Conclusions Apart from NIHSS score, BNP was a very useful predictor for long-term outcomes of patients with NVAF after AIS.

Prognostic Value of Serum D-Dimer in Noncardioembolic Ischemic Stroke

Article

Sep 2016

Background: Although D-dimer levels are significantly associated with cardioembolic infarction, the significance of D-dimer levels in relation to the severity and functional outcomes of other stroke subtypes, such as lacunar and large artery atherosclerosis infarction, remains unclear. The purpose of this study was to evaluate whether elevated initial D-dimer levels are significantly and cross-sectionally associated with poor functional outcomes at each time point during a 9-month follow-up period. We also investigated the significance of D-dimer levels in longitudinal temporal changes of functional outcomes in these patients. Methods: We recruited 146 patients with lacunar infarction and 161 patients with large artery atherosclerosis infarction who were consecutively admitted to our hospital after acute stroke. Serum D-dimer levels were evaluated initially and the modified Rankin scale were measured initially and at 1-, 3-, 6-, and 9-month follow-up visits. Results: Patients with higher D-dimer levels had significantly worse initial functional outcomes, and these worse outcomes were maintained throughout the 9-month follow-up period compared with the low D-dimer group. However, regardless of stroke subtype, D-dimer levels did not influence long-term changes in functional outcomes over the 9-month follow-up period. Conclusion: This study suggests that elevated D-dimer levels can be used as a surrogate marker for poor functional outcomes only during the acute stage. Further evaluation of serum D-dimer levels could provide a helpful predictive marker for stroke prognosis.

Diagnostic Value of Elevated D-Dimer Level in Venous Thromboembolism in Patients With Acute or Subacute Brain Lesions

Article

Full-text available

Dec 2015

Objective: To define the risk factors that influence the occurrence of venous thromboembolism (VTE) in patients with acute or subacute brain lesions and to determine the usefulness of D-dimer levels for VTE screening of these patients. Methods: Medical data from January 2012 to December 2013 were retrospectively reviewed. Mean D-dimer levels in those with VTE versus those without VTE were compared. Factors associated with VTE were analyzed and the odds ratios (ORs) were calculated. The D-dimer cutoff value for patients with hemiplegia was defined using a receiver operating characteristic (ROC) curve. Results: Of 117 patients with acute or subacute brain lesions, 65 patients with elevated D-dimer levels (mean, 5.1±5.8 mg/L; positive result >0.55 mg/L) were identified. Logistic regression analysis showed that the risk of VTE was 3.9 times higher in those with urinary tract infections (UTIs) (p=0.0255). The risk of VTE was 4.5 times higher in those who had recently undergone surgery (p=0.0151). Analysis of the ROC showed 3.95 mg/L to be the appropriate D-dimer cutoff value for screening for VTE (area under the curve [AUC], 0.63; 95% confidence interval [CI], 0.5-0.8) in patients with acute or subacute brain lesions. This differs greatly from the conventional D-dimer cutoff value of 0.55 mg/L. D-dimer levels less than 3.95 mg/L in the absence of surgery showed a negative predictive value of 95.8% (95% CI, 78.8-99.8). Conclusion: Elevated D-dimer levels alone have some value in VTE diagnosis. However, the concomitant presence of UTI or a history of recent surgery significantly increased the risk of VTE in patients with acute or subacute brain lesions. Therefore, a different D-dimer cutoff value should be applied in these cases.

Ischemic Stroke

Article

Jan 2015

In recent years, there was a surge in interest for biomarkers in ischemic stroke, with several purposes. In this chapter we will focus on biomarkers with potential use in ischemic stroke, namely, in diagnosis, grading of severity, identification of subtypes, and prediction of outcome or recurrence. A special emphasis will be placed on the role of inflammation in stroke, as it plays a key role in the cascade of events leading to progression of ischemic brain injury. However, the role of biomarkers in the clinical management of ischemic stroke is still limited. Therapeutic trials attempting to intervene on the inflammatory process are also briefly mentioned.

Embolic Stroke Diagnosed by Elevated D-Dimer in a Patient With Negative TEE for Cardioembolic Source

Article

Full-text available

Oct 2015

We report a case of cerebrovascular accident with thromboembolic stroke etiology in a patient who had atrial flutter and negative transesophageal echocardiography (TEE) results. The increased D-dimer levels (1877 ng/mL) initiated referral for magnetic resonance imaging and magnetic resonance angiography of the brain that showed classic recanalization of an embolic thrombus in the angular branch of the left middle cerebral distribution. The D-dimer level of this patient was normalized after 3 months of anticoagulation therapy. Although TEE is considered the gold standard for evaluation of cardiac source of embolism, exclusion of intracardiac thrombus with TEE alone does not eliminate the risk of thromboembolic events. This case highlights the utility of D-dimer as a potential adjunct in the decision-making process to guide investigation of thromboembolism, determine subsequent therapy, and hence reduce the risk of embolic stroke recurrence.

The Predictive Value of CT Perfusion Parameters Combined with D-Dimer in Hemorrhagic Transformation after Thrombolysis in Acute Ischemic Stroke

Article

Full-text available

Jan 2024

丹刘

The role of D-dimer in stroke risk stratification in patients with atrial fibrillation

Article

Jul 2022

Introduction. D-dimer is an important indicator, which reflects the activation of intravascular blood coagulation and fibrinolytic system. There are some data confirming that D-dimer is associated with stroke development in patients with atrial fibrillation. However, D-dimer is not included in modern stoke risk stratification scales in patients with atrial fibrillation. Aim — to analyze the data devoted to the role of D-dimer in stroke risk stratification in patients with atrial fibrillation. General findings. D-dimer, despite several limitations, could be used in clinical practice as an indicator that is associated with stroke development in patients with atrial fibrillation. D-dimer level estimation could help to decide whether to use anticoagulant treatment in patients with low risk of stroke development or in those patients with a single non-sex CHA 2 DS 2 -VASc score risk factor.

High D-Dimer Concentration Is a Significant Independent Prognostic Factor in Patients with Acute Large Vessel Occlusion Undergoing Endovascular Thrombectomy

Article

Jan 2022

Objective This study aimed to investigate prognostic factors that affect modified Rankin Scale (mRS) score at 3 months after onset in acute stroke patients with large vessel occlusion (LVO) undergoing endovascular thrombectomy. Methods We retrospectively examined 87 consecutive patients who underwent endovascular cerebral thrombectomy for acute anterior circulation LVO at Oita University Hospital and Nagatomi Neurosurgery Hospital from January 2014 to December 2020. Results Age, National Institutes of Health Stroke Scale (NIHSS) score, and D-dimer concentration on admission were significant univariate prognostic factors related to mRS score 3 months after stroke onset. Multivariate logistic regression analysis showed that D-dimer concentration was the only significant independent prognostic factor. The area under the receiver operating characteristic curve for D-dimer concentration and mRS score at 3 months was 0.715 (95% confidence interval, 0.599 - 0.831); sensitivity and specificity were 60.6% and 80.0%, respectively, using a 1.9 μg/mL cutoff value. Conclusions Prognosis may be worse in patients undergoing acute endovascular cerebral thrombectomy with high D-dimer concentration on admission. Other treatment options should be considered for these patients.

Preoperative plasma D-dimer level may be predictive for success of cerebral reperfusion and outcome after emergency mechanical thrombectomy for intracranial large vessel occlusion

Article

Mar 2022
J CLIN NEUROSCI

Presented retrospective analysis evaluated whether preoperative plasma D-dimer level may predict the success of cerebral reperfusion and outcome after emergency mechanical thrombectomy (MT) for intracranial large vessel occlusion (ILVO). Study cohort comprised 121 patients (mean age, 76 ± 12 years) from two participating centers. ILVO mostly affected the M1 segment (48 cases) and internal carotid artery (ICA; 37 cases). Mean preoperative National Institutes of Health Stroke Scale (NIHSS) score was 18 ± 8. Mean preoperative plasma D-dimer level was 4.4 ± 6.6 μg/ml. In 88 patients (73%) MT resulted in successful cerebral reperfusion. Multivariate analysis revealed independent associations of non-successful cerebral reperfusion with preoperative plasma D-dimer level > 6.7 μg/ml (P = 0.0021), location of ILVO other than ICA (P = 0.0056), and prolonged antiplatelet or anticoagulant therapy before stroke onset (P = 0.0172). Plasma D-dimer level ≤ 6.7 μg/ml predicted successful cerebral reperfusion with 0.91 sensitivity and 0.36 specificity. In 39 patients (32%) treatment resulted in favorable outcome. Multivariate analysis revealed independent associations of the unfavorable outcome with non-successful cerebral reperfusion after MT (P = 0.0005), preoperative plasma D-dimer level > 1.9 μg/ml (P = 0.0131), higher preoperative NIHSS score (P = 0.0171), and chronic arterial hypertension before stroke onset (P = 0.0254). Plasma D-dimer level ≤ 1.9 μg/ml predicted favorable outcome with 0.64 sensitivity and 0.62 specificity. In conclusion, preoperative plasma D-dimer level may be predictive for success of cerebral reperfusion and outcome after emergency MT for ILVO, which may be potentially helpful for prediction of prognosis in selected treatment candidates.

Generation of a Monoclonal Antibody against D-Dimer Using HTS-Based LiCA

Article

Full-text available

Sep 2019

D-dimer is an essential diagnostic index of thrombotic diseases. Since the existing anti-D-dimer antibodies vary in quality and specificity, a search for alternative anti-D-dimer antibodies is required. The present study aimed to screen a novel monoclonal antibody (mAb) against D-dimer using a light-initiated chemiluminescence assay (LiCA). In this work, mice were immunized with antigen prepared from human plasma by enzyme hydrolysis. After screening, a novel mAb, DD 2G11, was obtained. The results of sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis indicated that DD 2G11 could be used as a standard marker for D-dimer. The isotype of DD 2G11 was IgG1, the K a value was 0.646 nM-1, and the K d value was 50 nM, indicating that the binding affinity to D-dimer was very high. Furthermore, no cross-reactivity between DD 2G11 and other fibrinogen degradation products (FgDPs) was found. Finally, the correlation between DD 2G11 and the reference antibody (commercial antibody) was investigated by analyzing 56 clinical samples using a latex-enhanced turbidimetric immunoassay (LTIA). The R ² value of the linear regression was 0.94538, indicating that DD 2G11 met clinical requirements. In conclusion, the present study provides a more expeditious protocol to screen mAbs and provides a clinically usable mAb against D-dimer.

The emerging value of serum D-dimer measurement in the work-up and management of ischemic stroke

Article

Sep 2019

Background Elevated D-dimer levels are a marker of both thrombin formation and fibrinolysis. Currently D-dimer measurement is routinely used for ruling out venous thromboembolism and diagnosis/monitoring of disseminated intravascular coagulation. Recent emerging data suggest that D-dimer may become an important biomarker in ischemic stroke as well as in cardiovascular diseases. Aims To outline the clinical utility of D-dimer in work-up and management of ischemic stroke. Summary D-dimer measurement is most useful in stroke with active cancer as it can confirm etiologic diagnosis, predict recurrent stroke risk, and aid treatment decision in cancer-associated stroke. In cryptogenic stroke, high D-dimer levels can also provide clues for the cause of stroke as occult cancer and undetected cardiac embolic source as occult atrial fibrillation and may be helpful in treatment decision making of secondary stroke prevention. Serial D-dimer measurements should be further studied to monitor antithrombotic therapy effectiveness in both cardiogenic and cryptogenic etiologies. Conclusion Accumulating data suggests the utility of D-dimer test in the management of ischemic stroke, although the evidence is still limited. Future studies would clarify the role of D-dimer measurement in ischemic stroke.

Development and validation of a risk score to predict 30-day mortality in patients with atrial fibrillation-related stroke: GPS-GF score

Article

Mar 2018

Objective Stroke due to atrial fibrillation (AF) is common and frequently devastating. However, there is no specific tool to accurately estimate the risk of mortality. This study aims to develop and validate a comprehensive risk score for predicting 30-day mortality in the patients with AF-related stroke. Methods A retrospective multi-center clinical study was performed based on the data from the project of secondary prevention of stroke in patients with nonvalvular AF in Shaanxi province, China. A total of 1077 consecutive patients were randomly classified into derivation (66.7%, n = 718) and internal validation cohort (33.3%, n = 359). Independent predictors of 30-day mortality were obtained using univariate and multivariable analyses. The area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow test were used to assess model discrimination and calibration, respectively. Results Two hundred patients (18.6%) of 1077 participants died within 30 days. An 8-point score was generated from the five independent predictors for 30-day mortality including Glasgow Coma Scale, pneumonia, midline shift on brain images, blood glucose, and female sex, which was named GPS-GF. The resulting score showed good discrimination (AUROC) and well calibrated (Hosmer–Lemeshow test) in the derivation (0.909; p = 0.102) and internal validation cohort (0.922; p = 0.153). Compared with iScore, the GPS-GF score exhibited remarkably better discriminative power and predictive accuracy regarding the 30-day mortality in patients with AF-related stroke. Conclusion The GPS-GF score is a simple and valid tool for predicting 30-day mortality in patients with AF-related stroke.

Assessment of thrombogenicity in stroke

Article

Jun 2017

Masako Yamazaki

D-dimer Predicts Short-Term Functional Outcome in Acute Ischemic Stroke

Article

Full-text available

Feb 2017

Background The objective of the study was to evaluate the predictive value of plasma D-dimer at admission after acute ischemic stroke, and to assess its effect on short-term functional outcome. Methods Fasting plasma D-dimer was measured in 290 consecutive patients (61.7% men, mean age 67.0±12.3 years) within 3 days after the onset of acute ischemic stroke. The outcomes were measured at 3-months after stroke onset, by the modified Rankin Scale (mRS). Results Atrial fibrillation, hypertension, diabetes and involvement of the insular cortex, the levels of serum high sensitive C-reactive protein and D-dimer, as well as incidence of women and age, were all significantly higher in the poor outcome group (P

Plasma D-dimer Level, the Promising Prognostic Biomarker for the Acute Cerebral Infarction Patients

Article

May 2016

Background: Despite being an important cause of death and functional disability, acute cerebral infarction (ACI) lacks accurate and easy tools to predict the outcome of patients beyond clinical variables such as age and stroke severity. Methods: To investigate if plasma D-dimer level can be used as such a prognostic biomarker for ACI, so as to better guide patients' management, we studied the association between plasma D-dimer and the functional recovery of 1173 ACI patients. The patients were divided into 2 groups according to modified Rankin Scale (mRS) scores or National Institutes of Health Stroke Scale (NIHSS) scores evaluated on the 30th day after onset. Results: We observed that plasma D-dimer level correlated significantly with the prognosis of ACI evaluated based on both mRS scores (389.68 ± 32.06 µg/L for poor prognosis versus 377.70 ± 32.68 µg/L for good prognosis, P < .001) and NIHSS scores (387.01 ± 30.60 µg/L for poor prognosis versus 375.23 ± 30.66 µg/L for good prognosis, P < .01). Logistic analysis confirmed that higher D-dimer level was a risk factor for poor prognosis (mRS: odds ratio [OR], 1.604; 95% confidence interval [CI], 1.360-1.892; P < .001; NIHSS: OR, 1.733; 95% CI, 1.461-2.056; P < .01), after adjusted for age, gender, hypertension, diabetes, smoking, and hyperlipidemia. Conclusion: Our results show that plasma D-dimer level is a promising prognosis biomarker for ACI.

D-Dimer versus International Normalized Ratio of Prothrombin Time in Ischemic Stroke Patients Treated with Sufficient Warfarin

Article

Apr 2016

Background: In patients receiving chronic warfarin therapy, the international normalized ratio of prothrombin time (PT-INR) reportedly correlates with the incidence, size, severity, and outcome of ischemic stroke, and thus there are guidelines for the optimal PT-INR range that is to be maintained during secondary or primary prevention of ischemic stroke. However, the details of ischemic stroke in patients in whom an optimal PT-INR is maintained by warfarin therapy have not been thoroughly investigated. We conducted a retrospective study to determine the predictors of the size, severity, and outcome of ischemic stroke occurring in patients under chronic warfarin therapy and maintenance of an optimum PT-INR. Methods: The study group comprised 22 consecutive acute ischemic stroke patients who were receiving warfarin and whose PT-INR was within the optimal range on admission. The PT-INR and plasma D-dimer level of these patients on admission were analyzed in relation to infarction volume, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale score at discharge. Results: PT-INR did not correlate with infarction volume, severity, or outcome. The D-dimer level correlated positively and significantly with the volume (r = .49, P < .05), severity (r = .54, P < .05), and outcome of ischemic stroke (r = .61, P < .01) and did not correlate with the PT-INR (r = -.27, P = .23). Conclusions: When the PT-INR is within optimal range in patients receiving chronic warfarin therapy but who suffer an ischemic stroke, the admission D-dimer level, but not PT-INR, correlates with the size, severity, and outcome of the stroke. Thus, monitoring the D-dimer level in patients receiving long-term warfarin therapy is important, regardless of whether the optimal PT-INR is maintained.

Relevance of transthoracic left atrial appendage wall velocity measurement in addition to left atrial volume for noninvasive and quantitative assessment of left atrial thrombogenesis in patients with atrial fibrillation and normal D-dimer levels

Article

Dec 2015

Purpose: This study examined the role of left atrial (LA) appendage wall velocity (LAAWV) measurement in addition to LA size for the noninvasive assessment of thrombogenesis in patients with atrial fibrillation (AF) and normal plasma D-dimer levels. Methods: In 58 non-valvular AF patients, LAAWV and the LA volume index (LAVI) were determined by transthoracic echocardiography. LA appendage flow velocity and severity of spontaneous echo contrast (SEC) were determined by transesophageal echocardiography. Results: LAAWV was strongly correlated with LA appendage flow velocity (r = 0.82), and LAVI was weakly correlated with LA appendage flow velocity (r = -0.37). As SEC severity increased, LAAWV decreased (p < 0.001) and LAVI increased (p < 0.001). Among 52 patients with normal D-dimer levels, LAAWV < 10 cm/s had 71 % sensitivity and 94 % specificity for diagnosing severe SEC. Severe SEC was not found in 18/32 large LAVI patients (>34 mL/m(2)), but 17 of the 18 patients (94 %) had LAAWV < 10 cm/s. Severe SEC was found in 3/20 patients with normal LAVI, but all of them showed LAAWV < 10 cm/s. Conclusion: The noninvasive measurement of transthoracic LAAWV in addition to LA volume is clinically relevant for quantitatively assessing thrombogenesis in AF patients with normal D-dimer levels.

Immune-Mediated Inflammatory Rheumatic Diseases

Article

Full-text available

Jan 2015

Atherosclerosis occurs earlier and progresses more rapidly in patients with immune-mediated inflammatory rheumatic disorders. Cardiovascular (CV) disease is the leading cause of death in this context, and the relative risk for CV events is strikingly high, especially among young women. This excessive risk is not fully explained by traditional CV risk factors, and the disease itself is of paramount relevance. Systemic inflammation enhances atherogenesis throughout the whole process. Circulating inflammatory cytokines foster early vascular dysfunction as well as subclinical structural lesions, plaque rupture and thrombosis. Several biomarkers of atherosclerosis have been identified in rheumatic diseases. With few exceptions, their applicability in clinical practice is still marginal.

Validation of Clinical Classification Schemes for Predicting Stroke

Article

Full-text available

Jun 2001

Context: Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. Objective: To assess the predictive value of classification schemes that estimate stroke risk in patients with AF. Design, setting, and patients: Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all 3 classification schemes were validated. The CHADS( 2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge. Main outcome measure: Hospitalization for ischemic stroke, determined by Medicare claims data. Results: During 2121 patient-years of follow-up, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the 2 existing classification schemes predicted stroke better than chance: c of 0.68 (95% confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95% CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. Conclusion: The 2 existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Accuracy of Transesophageal Echocardiography for Identifying Left Atrial Thrombi: A Prospective, Intraoperative Study

Article

Dec 1995

Warren Manning

Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation

Article

Jun 2007

Robert G Hart

Background: Atrial fibrillation is a strong independent risk factor for stroke. Purpose: To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis. Data Sources: Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language. Study Selection: All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation. Data Extraction: Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death. Data Synthesis: Twenty-nine trials included 28044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% Cl, 49% to 74%) and 22% (Cl, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [Cl, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (≤0.3% per year) on the basis of meta-analysis. Limitation: Methodological features and quality varied substantially and often were incompletely reported. Conclusions: Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.

Study of Hemostatic Biomarkers in Acute Ischemic Stroke by Clinical Subtype

Article

Apr 2012

We studied the usefulness of hemostatic biomarkers in assessing the pathology of thrombus formation, subtype diagnosis, prognosis in the acute phase of cerebral infarction, and differences between various hemostatic biomarkers. Our study included 69 patients with acute cerebral infarction who had been hospitalized within 2 days of stroke onset. Fibrin monomer complex (FMC), soluble fibrin (SF), D-dimer, thrombin-antithrombin III complex, fibrinogen, antithrombin III, and fibrin/fibrinogen degradation products (FDPs) were assayed as hemostatic biomarkers on days 1, 2, 3, and 7 of hospitalization. In the cardioembolic (CE) stroke group, FMC and SF levels were significantly higher on days 1 and 2 of hospitalization, and D-dimer levels were significantly higher on day 1 of hospitalization, compared to the noncardioembolic (non-CE) stroke group. FDP levels were significantly higher at all times in the CE group compared to the non-CE group. Neither the National Institute of Health Stroke Scale (NIHSS) used during hospitalization nor the modified Rankin Scale (mRS) used at discharge found any significant correlations to hemostatic biomarkers, but the NIHSS score during hospitalization was significantly higher in the CE group than in the non-CE group. Measurements of hemostatic biomarkers, such as FMC, SF, and D-dimer on the early stage of cerebral infarction are useful for distinguishing between CE and non-CE stroke.

Progress for Stroke Prevention With Atrial Fibrillation Emergence of Alternative Oral Anticoagulants

Article

Apr 2012
STROKE

Atrial fibrillation (AF) is both a common cardiac arrhythmia and a frequent cause of cardioembolic strokes. The prevalence of AF markedly increases with age and with the current population trends, the number of patients with AF is expected to continue to grow and may reach 12 million in the United States by 2050.1 AF accounts for up to 20% of all ischemic strokes and independently increases the risk of these events by up to 5-fold.2,3 Various cardiovascular risk factors do increase the risk of AF and given the continuing rise of obesity and resultant hypertension and diabetes, the future healthcare burden of AF-related strokes is likely to greatly increase. AF is arguably 1 of the best-studied causes of stroke with dozens of randomized trials that have led to well-established evidence-based recommendations regarding effective treatment modalities. Warfarin, a vitamin K antagonist, is currently the most commonly used oral anticoagulant. It has been used for decades, is inexpensive, and has standardized laboratory monitoring and reversal protocols. Warfarin is also exceedingly effective; a recent meta-analysis has shown it to reduce stroke by almost two thirds compared with placebo and to provide an almost 40% relative risk reduction compared with antiplatelet therapy.4 Warfarin, however, has several limitations that have led to underuse in the community. It has a very narrow therapeutic window with potentially life-threatening consequences from both under- and overdosing the medication. Bleeding, either systemically or intracranially, is the most feared complication; it has hindered a more wide-scale acceptance of this therapy, particularly among elderly patients. Maintaining most patients within that therapeutic window is challenging due to numerous drug and diet interactions and requires frequent and inconvenient blood testing and monitoring. Due to these difficulties, a portion of patients and physicians has never adequately adopted this therapy, which …

Anticoagulation Control Quality Affects the D-Dimer Levels of Atrial Fibrillation Patients

Article

Dec 2011
CIRC J

Anticoagulation control quality affects the incidence of thromboembolic events in atrial fibrillation (AF) patients. However, the effects of anticoagulation control quality on the prothrombotic state of AF patients are unclear. Ninety-five AF patients who had been treated with warfarin were prospectively followed-up for 449 ± 92 days. We analyzed whether time in the therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, percentage of INR values in the range (%INR), and coefficient of variation of INR values (CV-INR) were related to D-dimer levels. The mean values of TTR, %INR, and CV-INR were 62%, 59%, and 0.19, respectively, and their median values were 67%, 63%, and 0.19, respectively. TTR was significantly correlated with %INR (R(2) = 0.917, P<0.01), but not with CV-INR (R(2) = 0.050, P = 0.26). The mean and median D-dimer levels were 0.79 and 0.60 µg/ml, respectively. Low TTR, low %INR, and high CV-INR were found to contribute to high D-dimer levels (P = 0.02, 0.03, and 0.02, respectively). In AF patients treated with warfarin, not only the duration outside the target INR range, but also the fluctuation in INR level may influence the prothrombotic state.

Atrial fibrillation

Article

Dec 2011
LANCET

The management of atrial fibrillation has evolved greatly in the past few years, and many areas have had substantial advances or developments. Recognition of the limitations of aspirin and the availability of new oral anticoagulant drugs that overcome the inherent drawbacks associated with warfarin will enable widespread application of effective thromboprophylaxis with oral anticoagulants. The emphasis on stroke risk stratification has shifted towards identification of so-called truly low-risk patients with atrial fibrillation who do not need antithrombotic therapy, whereas oral anticoagulation therapy should be considered in patients with one or more risk factors for stroke. New antiarrhythmic drugs, such as dronedarone and vernakalant, have provided some additional opportunities for rhythm control in atrial fibrillation. However, the management of the disorder is increasingly driven by symptoms. The availability of non-pharmacological approaches, such as ablation, has allowed additional options for the management of atrial fibrillation in patients who are unsuitable for or intolerant of drug approaches.

D-Dimer for risk stratification in patients with acute pulmonary embolism

Article

Nov 2011
J THROMB THROMBOLYS

Risk stratification is currently recommended for the initial management of patients with acute pulmonary embolism (PE). We performed a meta-analysis of studies in patients with acute PE to assess the prognostic value of elevated D-dimer levels for short-term (within 30 days) and 3-month mortality. The association between D-dimer levels and markers of PE severity was also reviewed. Unrestricted searches were performed using the terms D-dimer and pulmonary embolism. Studies reporting on D-dimer levels and mortality and/or markers of PE severity were included in the review. A random-effects model was used to pool study results, funnel-plot inspection to evaluate publication bias and I squared testing to test for heterogeneity. Five studies (2,885 patients) reported on D-dimer levels and short-term mortality. D-dimer levels above a prognostic cut-off were significantly associated with short-term mortality in the overall population (OR: 2.76; 95% CI: 1.83-4.14; I(2) = 0%) and in hemodynamically stable patients (three studies, 874 patients; OR: 4.28; 95% CI: 1.88-9.71; I(2) = 0%). Four studies (1,254 patients) reported on D-dimer levels and 3-month mortality. D-dimer levels above a prognostic cut-off were associated with 3-month mortality (OR: 4.29; 95% IC: 1.70-10.79; I(2) = 0%). Overall, 14 studies assessed the association between D-dimer and markers of PE severity. An association has been observed between D-dimer levels and the degree of pulmonary artery obstruction. In patients with acute PE elevated D-dimer is associated with increased short-term and 3-month mortality, suggesting the potential of using this test for both diagnosis and risk stratification.

Preadmission Therapeutic Anticoagulation Reduces Cerebral Infarct Volume in Patients with Nonvalvular Atrial Fibrillation

Article

Oct 2011
EUR NEUROL

We investigated the influence of preadmission anticoagulation on infarct volume in patients with nonvalvular atrial fibrillation (NVAF). Data were collected on consecutive ischemic stroke patients with NVAF admitted to Osaka University Hospital between 2004 and 2011. Patients were divided into 3 groups: the no-anticoagulation group, the subtherapeutic anticoagulation group [admission prothrombin time international normalized ratio (PT-INR) <1.6], and the therapeutic anticoagulation group (PT-INR ≥1.6). In analyses of neurological outcome, we excluded patients with a modified Rankin Scale (mRS) score of >1 before onset. Of the 68 patients, 45 were classified into the no-anticoagulation group, 9 into the subtherapeutic group, and 14 into the therapeutic group. The median value of infarct volume was 60 (interquartile range 9-176), 142 (64-184), and 8 (3-46) ml in each group, respectively. Infarct volume in the therapeutic group was significantly smaller than in the subtherapeutic group (p = 0.010), and tended to be smaller than in the no-anticoagulation group (p = 0.086). National Institute of Health Stroke Scale score at admission, and mRS score at discharge were significantly reduced in the therapeutic group compared with those in the other groups (p = 0.028 and p = 0.017, respectively). Therapeutic anticoagulation reduces infarct volume and improves neurological outcome after ischemic stroke in patients with NVAF.

Early neurological outcomes according to CHADS2 score in stroke patients with non-valvular atrial fibrillation

Article

Sep 2011
EUR J NEUROL

A higher CHADS(2) score or CHA(2)DS(2)-VASc score is associated with an increased risk of ischaemic stroke in patients with non-valvular atrial fibrillation (NVAF). However, there are no data regarding early neurological outcomes after stroke according to the risk levels. In this study, a total of 649 stroke patients with NVAF were enrolled and categorized into three groups: low-risk (CHADS(2) score of 0-1), moderate-risk (CHADS(2) score 2-3), or high-risk group (CHADS(2) score ≥4). CHA(2)DS(2)-VASc score was divided into four groups including 0-1, 2-3, 4-5, and ≥6. We investigated whether there were differences in initial stroke severity, early neurological outcome, and infarct size according to CHADS(2) score or CHA(2)DS(2)-VASc score in stroke patients with NVAF. The initial National Institutes of Health Stroke Scale (NIHSS) score was highest in high-risk group [9.5, interquartile range (IQR) 4-18], followed by moderate-risk (8, IQR 2-17) and low-risk group (6, IQR 2-15) (P=0.012). Likewise, initial stroke severity increased in a positive fashion with increasing the CHA(2)DS(2)-VASc score. During hospitalization, those in the high-risk group or higher CHA(2)DS(2)-VASc score had less improvement in their NIHSS score. Furthermore, early neurological deterioration (END) developed more frequently as CHADS(2) score or CHA(2)DS(2)-VASc score increased. Multivariate analysis showed being in the high-risk group was independently associated with END (OR 2.129, 95% CI 1.013-4.477). Our data indicate that patients with NVAF and higher CHADS(2) score or CHA(2)DS(2)-VASc score are more likely to develop severe stroke and a worse clinical course is expected in these patients after stroke presentation.

D-Dimer Testing in Laboratory Practice *

Article

Jun 2011
CLIN CHEM

Armando Tripodi

D-dimer is a reliable and sensitive index of fibrin deposition and stabilization. As such, its presence in plasma should be indicative of thrombus formation. There are many conditions unrelated to thrombosis in which D-dimer concentrations are high, however, making its positive predictive value rather poor. Notwithstanding these limitations, D-dimer can be regarded as a most valuable laboratory tool to diagnose and manage a vast array of thrombosis-related clinical conditions, including (a) diagnosis of venous thromboembolism (VTE), (b) identification of individuals at increased risk of first thrombotic event (both arterial and venous), (c) identification of individuals at increased risk of recurrent VTE, (d) establishment of the optimal duration of secondary prophylaxis after a first episode of VTE, (e) pregnancy monitoring, and (f) diagnosis/monitoring of disseminated intravascular coagulation (DIC). This article is aimed at reviewing the merits and pitfalls of these applications. From my analysis of the literature, I draw the following conclusions. (a) D-dimer, as measured by a sensitive test, can be safely used to exclude VTE in symptomatic outpatients, provided that it is used in combination with the pretest clinical probability. (b) High concentrations of D-dimer are associated with an increased risk of recurrent VTE. (c) Patients who present with D-dimer above cutoff after stopping the regular course of oral anticoagulation benefit from extended prophylaxis. (d) Finally, D-dimer can be used as a fibrin-related degradation marker for the diagnosis/management of patients with DIC.

Pre-admission CHADS(2) score is related to severity and outcome of stroke

Article

May 2011

The CHADS(2) score is a stroke risk stratification system for patients with atrial fibrillation (AF). The relationship between the pre-admission CHADS(2) score and stroke severity or outcome was examined in AF-related cardioembolic stroke patients. 423 consecutive AF-related cardioembolic stroke patients (250 men, 173 women; aged 76±10 years) were reviewed. Pre-admission CHADS(2) scores of 0, 1, 2, 3, 4, 5, and 6 were present in 4.3%, 21.0%, 34.3%, 23.6%, 11.8%, 4.5%, and 0.5% of patients, respectively. There were significant correlations (P<0.001) between CHADS(2) and National Institutes of Health Stroke Scale (NIHSS) scores on admission, and CHADS(2) and modified Rankin scale (mRS) scores at discharge. The optimal cutoff CHADS(2) score for an mRS score ≥3 was ≥2 (sensitivity 84%, specificity 38%). For death, the optimal cutoff CHADS(2) score was ≥3 (sensitivity 59%, specificity 62%). On multivariate analysis, a CHADS(2) score ≥2 was independently associated with an mRS score ≥3 (OR 1.93, 95% CI 1.39-2.72, P<0.001), and a CHADS(2) score ≥3 was independently associated with death (OR 1.46, 95% CI 1.02-2.11, P=0.038). The CHADS(2) score is related to severity and outcomes of stroke in patients with AF.

D-dimer levels and stroke progression in patients with acute ischemic stroke and atrial fibrillation

Article

Jul 2011
ACTA NEUROL SCAND

Patients with acute ischemic stroke and atrial fibrillation are at increased risk of stroke progression and recurrence. We sought to assess whether D-dimer and other markers of hemostatic activation could predict these adverse events in such patients. Blood samples were obtained from patients included in the Heparin in Acute Embolic Stroke Trial. Stroke progression was defined as a ≥3-point worsening on the Scandinavian Stroke Scale during the first 48 h after randomization. Blood samples were analyzed for D-dimer, prothrombin fragment 1 + 2, soluble fibrin monomer, and C-reactive protein. A total of 382 patients were included in the analyses. Levels of D-dimer and other markers of hemostatic activation were not significantly higher in patients with stroke progression than in other patients (D-dimer median values: 1025 ng/ml vs 970 ng/ml, P = 0.73). The same was true for recurrent stroke (D-dimer: 720 ng/ml vs 973 ng/ml, P = 0.96), and the combined endpoint of stroke progression, recurrent stroke, and death (D-dimer: 991 ng/ml vs 970 ng/ml, P = 0.91). Multivariable analyses did not alter the results. D-dimer and other markers of hemostatic activation were not associated with stroke progression, recurrent stroke, or death in patients with acute ischemic stroke and atrial fibrillation.

Relation of Effective Anticoagulation in Patients With Atrial Fibrillation to Stroke Severity and Survival (from the National Acute Stroke Israeli Survey [NASIS])

Article

Feb 2010

Although the benefit of antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is well recognized, its potential effect on stroke severity and outcome is less well established. Our objective was to examine the effect of preadmission antithrombotic therapy on stroke severity and outcome in patients with AF within a large comprehensive nationwide stroke survey. The data from consecutive patients with AF admitted with acute ischemic stroke or transient ischemic attack during a 2-month period were collected. The patients were categorized into 4 groups according to the use of preadmission antithrombotic therapy: no antithrombotic therapy, antiplatelet therapy, warfarin with an admission international normalized ratio (INR) <2 and INR of > or = 2. Of 1,938 patients presenting with acute brain ischemia, 329 (17%) had AF. The age-adjusted rate of more severe stroke (baseline National Institutes of Health stroke scale score >5) stratified by antithrombotic therapy use was 70% for no antithrombotic therapy use, 55% for antiplatelet therapy use, 59% for warfarin with an INR <2, and 38% for warfarin with an INR of > or = 2 (p = 0.01). Compared to warfarin therapy with an admission INR of > or = 2, the adjusted odds ratio for more severe strokes was 4.0 (95% confidence interval [CI] 1.7 to 10.0) for no antithrombotic therapy, 2.2 (95% CI 1.0 to 9.4) for antiplatelet therapy, and 2.7 (95% CI 1.1 to 6.7) for warfarin therapy with an INR of <2. Similarly, graded associations of antithrombotic medication were observed with severe disability (modified Rankin Scale score >3) or death at discharge, with corresponding adjusted odds ratios of 4.1 (95% CI 1.8 to 9.9), 2.1 (95% CI 1.0 to 4.6), and 1.5 (95% CI 0.6 to 3.5), and 1-year mortality, with corresponding adjusted ORs of 2.4 (95% CI 0.9 to 6.7), 1.9 (95% CI 0.8 to 5.0), and 2.2 (95% CI 0.8 to 6.2). In conclusion, in addition to its established benefit for stroke prevention, effective anticoagulation therapy is associated with decreased stroke severity and better functional outcome and survival in patients with AF presenting with acute brain ischemia.

The Benefits of Intravenous Thrombolysis Relate to the Site of Baseline Arterial Occlusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET)

Article

Feb 2010
STROKE

In ischemic stroke, the site of arterial obstruction has been shown to influence recanalization and clinical outcomes. However, this has not been studied in randomized controlled trials, nor has the impact of arterial obstruction site on reperfusion and infarct growth been assessed. We studied the influence of site and degree of arterial obstruction patients enrolled in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). EPITHET was a prospective, randomized, placebo-controlled trial of intravenous tissue plasminogen activator (tPA) in the 3- to 6-hour time window. Arterial obstruction site and degree were rated on magnetic resonance angiography blinded to treatment allocation and outcomes. In 101 EPITHET patients, 87 had adequate quality magnetic resonance angiography, of whom 54 had baseline arterial obstruction. Infarct growth attenuation was greater in those with tPA treatment compared to placebo among patients with middle cerebral artery (MCA) obstruction (P=0.037). The treatment benefit of tPA over placebo in attenuating infarct growth was greater for MCA than internal carotid artery (ICA) obstruction (P=0.060). With tPA treatment, good clinical outcome was more likely with MCA than with ICA obstruction (P=0.005). Most patients with ICA obstruction did not achieve good clinical outcome, whether treated with tPA (100%) or placebo (77%). The study was underpowered to prove any treatment benefit of tPA among patients with any or severe degree of arterial obstruction. Arterial obstruction site strongly predicts outcomes. ICA obstruction carries a uniformly poor prognosis, whereas good outcomes with MCA obstruction are associated with tPA therapy.

Preadmission Use of Warfarin Improves Short-Term Outcome in Patients with Acute Cerebral Infarction The Bergen Stroke Study

Article

May 2009
CEREBROVASC DIS

We hypothesized that patients with cerebral infarction on preadmission warfarin have less severe neurological deficits on admittance, less severe neurological deficits 1 week after the onset of cerebral infarction and a larger improvement as to neurological deficits within 1 week of acute cerebral infarction. All patients with cerebral infarction who did not receive thrombolytic treatment were included. Preadmission use of warfarin was registered. The National Institute of Health Stroke Scale (NIHSS) score was obtained on admittance and 7 days after stroke onset. In total, 42 patients (8.1%) used warfarin at the time of stroke onset. The mean NIHSS score on admittance was 6.9 among the patients on warfarin and 5.2 among those without warfarin (p = 0.10). The 1-week improvement in the NIHSS score was 3.5 among the patients on warfarin and 0.8 among the participants without warfarin (p < 0.001). Linear regression showed that a low NIHSS score on day 7 was independently associated with a low NIHSS score on admittance (p < 0.001), low age (p = 0.002) and preadmission use of warfarin (p < 0.001). Preadmission warfarin was not associated with less severe neurological deficits on admittance. However, it was related to both less severe neurological deficits 1 week after the onset of cerebral infarction and larger improvement as to neurological deficits within 1 week of acute cerebral infarction.

Associations of Inflammatory and Haemostatic Biomarkers with Poor Outcome in Acute Ischaemic Stroke

Article

Mar 2009
CEREBROVASC DIS

Many inflammatory and haemostatic biomarkers show associations with acute ischaemic stroke outcome, but few studies compare a large range of markers. We assessed clinical status and 16 biomarkers within 24 h of onset in 180 consecutive acute ischaemic stroke patients. A total of 94 patients had a poor outcome (dead or dependent at 30 days). C-reactive protein (CRP), IL-6, and fibrin D-dimer showed the strongest univariate associations with poor outcome (>2-fold increase; p < 0.01). When all biomarkers were included with clinical variables in a multivariable model, only D-dimer (OR 1.54; 95% CI 1.09-2.17), CRP (OR 1.31; 95% CI 1.03-1.68) and Scandinavian Stroke Scale (OR 0.91; 95% CI 0.88-0.95) were associated with poor outcome. D-dimer and CRP are independently associated with poor outcome in acute ischaemic stroke. More data is required to expand our understanding of these potential relationships with outcome.

Prevalence of atrial fibrillation in the general population of Japan: An analysis based on periodic health examination

Article

Aug 2008

The mortality and morbidity rates of various cardiovascular diseases differ between Western countries and Japan. The age- and gender-specific prevalence rate of atrial fibrillation (AF) in the general population of Japan was determined using the data from periodic health examinations in 2003. Data of 630,138 subjects aged 40 years or more (47% were men and 34% were employees of companies and local governments) were collected from northern to southern Japan. The prevalence of diagnosed AF in each 10-year age group of both men and women was determined. Based on these prevalence rates and the Registry of Residents, the number of people having AF in Japan was estimated. The prevalence rate of AF increased as both male and female subjects aged, and it was 4.4% for men but only 2.2% for women aged 80 years or more (p<0.0001). As a whole, the AF prevalence of men was three times that of women (1.35 versus 0.43%, p<0.0001). There may be approximately 716,000 people (95% confidence interval (CI), 711,000-720,000) with AF in Japan, an overall prevalence of 0.56%. The number of people having AF was projected to be 1.034 (95% CI, 1.029-1.039) million, an overall prevalence of 1.09%, in 2050. The prevalence of AF increased in Japan as the population aged, as in Western countries. The overall prevalence of AF in Japan is approximately two-thirds of that in the USA. The projected increase in the number of people having AF is modest in Japan in 2050.

Epidemiological assessment of chronic atrial fibrillation and risk of stroke. The Framingham Study

Article

Nov 1978

Chronic atrial fibrillation (AF) as a precursor of stroke was assessed over 24 years of follow-up of the general population sample at Framingham, Massachusetts. Persons with chronic established AF, with or without rheumatic heart disease (RHD), are at greatly increased risk of stroke, and the stroke is probably due to embolism. Chronic AF in the absence of RHD is associated with more than a fivefold increase in stroke indicence, while AF with RHD has a 17-fold increase. Stroke occurrence increased as duration of AF increased, with no evidence of a particularly vulnerable period. Chronic idiopathic AF is an important precursor of cerebral embolism. Controlled trials of anticoagulants or antiarrhythmic agents in persons with chronic AF may demonstrate if strokes can be prevented in this highly susceptible group.

Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation

Article

Feb 1990

We studied whether hemostatic abnormalities contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation. Hemostatic function was studied in four age-matched groups: 20 patients with nonvalvular atrial fibrillation and a previous ischemic stroke, 20 patients with nonvalvular atrial fibrillation without a previous stroke, 20 stroke patients with sinus rhythm, and 40 healthy controls. Both groups with nonvalvular atrial fibrillation had significantly higher concentrations of von Willebrand factor, factor VIII:C, fibrinogen, D-dimer (a fibrinolytic product), beta-thromboglobulin, and platelet factor 4; a significantly higher fibrinogen/antithrombin ratio; and significantly higher spontaneous amidolytic activity than the healthy controls. Prekallikrein levels were significantly lower in both groups with nonvalvular atrial fibrillation. Stroke patients with sinus rhythm had normal hemostatic function, normal concentrations of platelet-related factors, and a slightly increased concentration of fibrinopeptide A compared with the healthy controls. Both groups with nonvalvular atrial fibrillation differed from the stroke patients with sinus rhythm as they did from the healthy controls. No difference in hemostatic function was seen between the nonvalvular atrial fibrillation patients with and without a previous ischemic stroke. Thus, alterations in hemostatic function may contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation.

Measurements of acute cerebral infarction: Lesion size by computed tomography

Article

Aug 1989

As part of a prospective therapy study of 65 patients with acute, nonhemorrhagic, cerebral infarction, computed tomographic scans of the head were obtained at admission, 7-10 days, and 3 months. The scans were analyzed for the presence, site, size, and volume measurement of the infarction. At 7-10 days, the mean infarction volume as measured by computed tomography was 55 cm3 or about 4 x 4 x 3.5 cm (range = 0-507 cm3). At 3 months, the mean infarction volume decreased by 25% to 41 cm3. For the 26 scans showing infarction at the time of admission, the mean lesion volume was 33 cm3 at admission, 51 cm3 at 7-10 days, and 49 cm3 at 3 months. With lesion size at 7-10 days expressed as percentage of total brain volume, the mean infarction size was only 5%. Of the 49 patients with lesions revealed by computed tomography at 7-10 days, 20 had an infarction of 1% or less of total brain volume, while only six had an infarction of 20% or more of total brain volume. The lesion volumes as measured by the 7-10-day computed tomography correlated with the neurologic examination scores on admission (Spearman's rank-order correlation = 0.78) and with the scores at 1 week (Spearman's rank-order correlation = 0.79).

Accuracy of transesophageal echocardiography for identifying left atrial thrombi: A prospective, intraoperative study

Article

Jan 1996

To determine the ability of transesophageal echocardiography to accurately identify or exclude left atrial thrombi. Prospective cohort study. University hospital. 231 consecutive patients having transesophageal echocardiography before elective repair or replacement of the mitral valve or excision of a left atrial tumor. Fifty-six percent of patients had a history of atrial fibrillation, and 17% had a history of thromboembolism. Identification of left atrial thrombi during transesophageal echocardiographic examination and comparison with direct near-simultaneous visualization during cardiac surgery. Transesophageal echocardiography identified 14 left atrial thrombi in 14 patients (6%). Thrombus size range from 3 to 80 mm. Surgery confirmed 12 of 14 thrombi (86%), including 9 thrombi confined to the left appendage. No additional thrombi were found on direct inspection of the atria (sensitivity, 100% [95% CI, 74% to 100%]; specificity, 99% [CI, 97% to 99.9%]; positive predictive value, 86% [12/14]; negative predictive value, 100% [217/217]; for a population that had a 5.2% prevalence of thrombi). All 12 surgically confirmed thrombi were identified by two independent observers. Neither thrombus seen by only a single observer on transesophageal echocardiography was confirmed during direct inspection of the atria at surgery. Transesophageal echocardiography is highly accurate for identifying left atrial thrombi and can be used clinically to exclude left atrial thrombi.

Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: The Northern Manhattan Stroke Study

Article

Apr 1994

To identify determinants of recurrence and mortality after ischemic stroke in a mixed-ethnic region. The determinants of ischemic stroke outcome are not uniformly characterized and will be of increasing importance as the frequency of ischemic stroke survivors increases in our aging population. A cohort of 323 patients (40% black, 34% Hispanic, 26% white) with cerebral infarction from northern Manhattan over age 39 were followed for a mean of 3.3 years, with only 6% lost to follow-up. Cumulative life table risk of mortality and recurrence was calculated. Risk factors classified at the time of index ischemic stroke were selected based on univariate analyses and then entered into a Cox proportional hazards model for mortality and for recurrence. The life table cumulative risk of mortality was 8% at 30 days, 22% at 1 year, and 45% at 5 years after ischemic stroke. The immediate cause of death was related to vascular disease in 60%. After age adjustment, the significant predictors of mortality were congestive heart failure (risk ratio [RR] = 2.6), admission glucose > 140 mg/dl (RR = 1.7), and presentation with either a large dominant, nondominant, or major basilar syndrome (RR = 2.0). Patients with a lacunar syndrome had a better survival (RR = 0.6). Recurrent strokes occurred in 72 patients. The life table cumulative risk of recurrence was 6% at 30 days, 12% at 1 year, and 25% at 5 years after ischemic stroke. Ethanol abuse (RR = 2.5), hypertension requiring discharge medications (RR = 1.6), and elevated blood glucose within 48 hours of index ischemic stroke (RR = 1.2 per 50 mg/dl) were the independent predictors of recurrence. Among 30-day survivors, the effect of ethanol abuse was greater (RR = 3.5), indicating its impact on late recurrence. After accounting for age and presenting syndrome, initial glucose predicts stroke mortality and recurrence after ischemic stroke. This association may reflect uncontrolled and undiagnosed diabetes in our urban population. Furthermore, ethanol abuse may be a determinant of ischemic stroke recurrence. Reduction of the stroke public health burden will require targeted modification of such conditions and behaviors.

Fibrin D-Dimer and -Thromboglobulin as Markers of Thrombogenesis and Platelet Activation in Atrial Fibrillation: Effects of Introducing Ultra Low-Dose Warfarin and Aspirin

Article

Sep 1996

Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P < .001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels. Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.

Medical Complications After Stroke : A Multicenter Study

Article

Jul 2000

This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts, " pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.

Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation

Article

Jul 2001

Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. To assess the predictive value of classification schemes that estimate stroke risk in patients with AF. Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all 3 classification schemes were validated. The CHADS( 2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge. Hospitalization for ischemic stroke, determined by Medicare claims data. During 2121 patient-years of follow-up, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the 2 existing classification schemes predicted stroke better than chance: c of 0.68 (95% confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95% CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. The 2 existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Embolus Location Affects the Sensitivity of a Rapid Quantitative d -dimer Assay in the Diagnosis of Pulmonary Embolism

Article

Feb 2002

D-dimer blood tests have been suggested to rule out pulmonary embolism. Despite evidence of the safety of withholding anticoagulant treatment in patients with suspected pulmonary embolism and a normal D-dimer assay result, clinicians remain reluctant to use a D-dimer assay as a sole diagnostic test. This prospective study in 314 consecutive inpatients and outpatients investigates the relation between the diagnostic accuracy of D-dimer plasma concentration and pulmonary embolus location. Plasma D-dimer levels were measured using a quantitative immunoturbidimetric method. A strict protocol of ventilation-perfusion scintigraphy, pulmonary angiography, and spiral computed tomography was used to arrive at a final diagnosis and to assess the largest pulmonary artery in which embolus was visible. The influence of embolus location on the diagnostic accuracy was evaluated using the Kruskal-Wallis test and receiver operator characteristics (ROC) analysis. There was a strong correlation between plasma D-dimer concentration and embolus location (Kruskal-Wallis, p < 0.001). Thus, the assay showed greater accuracy in excluding segmental or larger emboli (sensitivity = 93%) than subsegmental emboli (sensitivity = 50%). D-dimer concentration and the accuracy of D-dimer assays are clearly dependent on embolus location and smaller, subsegmental emboli may be missed when D-dimer assays are used as a sole test to exclude pulmonary embolism.

Sequential alterations in haemorheology, endothelial dysfunction, platelet activation and thrombogenesis in relation to prognosis following acute stroke: The West Birmingham Stroke Project

Article

Jun 2002

Abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial function [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and thrombogenesis [plasminogen activator inhibitor (PAI), and fibrin D-dimer] are common in cardiovascular disease. We investigated changes in these markers in 86 patients (58 males) presenting with acute stroke (all age < 75 years, with ictus < 12 h), and sequential changes at six time points (baseline on admission, 48 h, 1 week, 2 weeks, 3 months and 6 months following the onset of stroke). Baseline plasma viscosity, haematocrit, fibrinogen, vWf, PAI, soluble P-selectin and fibrin D-dimer levels were increased in the acute stroke patients compared with 35 age-matched and sex-matched controls. Following admission, there were significant increases in haematocrit at 2 weeks, vWf at 48 h and 1 week, fibrinogen at 1 week, PAI at 48 h and 1 and 2 weeks, soluble P-selectin at 48 h, and fibrin D-dimer at 48 h and 1 week following admission. Using univariate 'time to event' analysis, high (> median) mean age (log-rank test, P = 0.0262), diastolic blood pressure (P = 0.01), haematocrit (P = 0.0234), PAI-1 (P = 0.0066) and fibrin D-dimer levels (P = 0.0356) were associated with a shortened event-free survival. Using a multivariate Cox survival analysis, only PAI-1 levels remained an independent predictor of survival (P = 0.0349). We conclude that acute stroke patients have marked baseline abnormalities of haemorheology, endothelial disturbance, thrombogenesis, platelet activation and abnormal fibrinolysis, with further changes over the subsequent follow-up period. Abnormal thrombogenesis and fibrinolysis may significantly influence survival in patients with acute stroke. These changes may have potential implications for the pathogenesis of stroke and its complications, although the possibility remains that we are documenting an acute phase response that previous studies, which included stroke patients with a wide time range since ictus onset, have neglected to consider.

Local intra-arterial thrombolysis in the carotid territory: Does recanalization depend on the thromboembolus type?

Article

Sep 2002

Little is known about whether recanalization of carotid territory occlusions by local intra-arterial thrombolysis (LIT) depends on the type of the occluding thromboembolus. We retrospectively analysed the records of 62 patients with thromboembolic occlusions of the intracranial internal carotid artery (ICA) bifurcation or the middle cerebral artery who were undergoing LIT with urokinase within 6 h of symptom onset. We determined the influence of thromboembolus type (according to the TOAST criteria), thromboembolus location, leptomeningeal collaterals, time interval from onset of symptoms to onset of thrombolysis, and patient's age on recanalization. The thromboembolus type was atherosclerotic in six patients, cardioembolic in 29, of other determined etiology in four, and of undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic occlusions were recanalized. The thromboembolus location but not the TOAST stroke type nor other parameters affected recanalization. In the TOAST group of patients with cardioembolic occlusions recanalization occurred significantly less frequently when transoesophageal echocardiography showed cardiac thrombus. The present study underlines the thromboembolus location as being the most important parameter affecting recanalization. The fact that thromboembolic occlusions originating from cardiac thrombi had a lower likelihood of being resolved by thrombolysis indicates the thromboembolus type as another parameter affecting recanalization.

Plasma Measurement of D-Dimer Levels for the Early Diagnosis of Ischemic Stroke Subtypes

Article

Dec 2002
ARCH INTERN MED

Different coagulation abnormalities according to stroke subtypes have been reported. We have assessed the clinical utility of D-dimer, a product of fibrin degradation, in the early diagnosis of stroke subtypes. Patients hospitalized after an acute ischemic cerebrovascular event underwent D-dimer assay (STA Liatest D-Dimer) (reference level, <0.50 micro g/mL) on days 1, 6 +/- 1, and 12 +/- 1 and were studied to identify stroke subtypes. We included 126 patients (mean age, 75.5 years) and 63 age-matched control subjects. Stroke subtypes were cardioembolic in 34 patients (27%), atherothrombotic in 34 (27%), lacunar in 31 (25%), and unknown in 27 (21%). At all 3 measurements, D-dimer levels were significantly higher in the cardioembolic group (mean +/- SEM, 2.96 +/- 0.51, 2.58 +/- 0.40, and 3.79 +/- 0.30 micro g/mL, respectively) than in the atherothrombotic (1.34 +/- 0.21, 1.53 +/- 0.26, and 2.91 +/- 0.23 micro g/mL, respectively) (P<.05) and lacunar (0.67 +/- 0.08, 0.72 +/- 0.15, and 0.64 +/- 0.06 micro g/mL, respectively) groups (P<.01). The difference was also significant between the latter 2 groups (P<.01). We found no difference between the lacunar group and controls (0.53 +/- 0.14 micro g/mL). According to day 1 measurements, the optimal cutoff point for predicting cardioembolic stroke was 2.00 micro g/mL, resulting in a specificity of 93.2% and in a sensitivity of 59.3%. For predicting lacunar stroke, the cutoff point was 0.54 micro g/mL, with a specificity of 96.2% and a sensitivity of 61.3%. The increasing use of the D-dimer assay in clinical practice could be extended to patients presenting with acute cerebrovascular ischemic events to help predict stroke subtype.

Effect of Intensity of Oral Anticoagulation on Stroke Severity and Mortality in Atrial Fibrillation

Article

Oct 2003
NEW ENGL J MED

The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR. We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files. Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0. Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation.

Blood Pressure Decrease During the Acute Phase of Ischemic Stroke Is Associated With Brain Injury and Poor Stroke Outcome

Article

Mar 2004
STROKE

Studies on the relation between blood pressure (BP) and stroke outcome have shown contradictory results. We explored the association of systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological deterioration, infarct volume, neurological outcome, and mortality at 3 months. We included 304 patients with acute ischemic stroke. SBP and DBP on admission and on the first day were the average values of all readings obtained in the emergency department and during a 24-hour period after patient allocation in the stroke unit. A U-shaped effect was observed: for every 10 mm Hg <or=180 mm Hg of SBP, the risk of early neurological deterioration, poor outcome, and mortality increased by 6%, 25%, and 7%, respectively, whereas for every 10 mm Hg >180 mm Hg, the risk of early neurological deterioration increased by 40% and the risk of poor outcome increased by 23%, with no effect on mortality. Mean infarct volume increased 7.3 and 5.5 cm(3) for every 10 mm Hg <or=180 and >180 mm Hg. A similar pattern was found in patients with DBP <or=100 or >100 mm Hg. These effects disappeared after adjustment for the use of antihypertensive drugs and BP drop >20 mm Hg within the first day, with the latter being the more important prognostic factor of poor outcome. High and low SBP and DBP, as well as a relevant drop in BP, are associated with poor prognosis in patients with ischemic stroke.

Hemostatic Function and Progressing Ischemic Stroke: D-dimer Predicts Early Clinical Progression

Article

Jul 2004
STROKE

Early clinical progression of ischemic stroke is common and is associated with increased risk of death and dependency. We hypothesized that activation of the coagulation system is an important contributor in some cases of deterioration. We aimed to characterize alterations in circulating hemostatic markers in patients with progressing stroke. Consecutive acute ischemic stroke admissions were recruited. Progressing stroke was defined by deterioration in components of the Scandinavian Stroke Scale. Hemostatic markers (coagulation factors VIIc, VIIIc, and IXc, prothrombin fragments 1+2 [F1+2], thrombin-antithrombin complexes [TAT], D-dimer, fibrinogen, von Willebrand factor [vWF] and tissue plasminogen activator) were measured within 24 hours of symptom recognition. Fifty-four (25%) of the 219 patients met criteria for progressing stroke. F1+2 (median 1.28 versus 1.06 nmol/L, P=0.01), TAT (5.28 versus 4.07 microg/L, P<0.01), D-dimer (443 versus 194 ng/mL, P<0.001) and vWF (216 versus 198 IU/dL, P<0.05) levels were higher in these patients than in stable/improving patients. In logistic regression analysis, with all important clinical and laboratory variables included, only natural log D-dimer (odds ratio [OR]: 1.87; 95% confidence interval [CI]: 1.38 to 2.54; P=0.0001) and mean arterial blood pressure (OR: 1.26 per 10 mm Hg change; 95% CI: 1.05 to 1.51; P=0.01) remained independent predictors of progressing stroke. There is evidence of excess thrombin generation and fibrin turnover in patients with progressing ischemic stroke. Measurement of D-dimer levels can identify patients at high risk for stroke progression. Further research is required to determine whether such patients benefit from acute interventions aimed at modifying hemostatic function.

Prothrombotic Activity Is Increased in Patients With Nonvalvular Atrial Fibrillation and Risk Factors for Embolism

Article

Sep 2004

The aim of this study was to investigate whether risk factors for embolism would promote thrombus formation in patients with nonvalvular atrial fibrillation (NVAF). Hemostatic markers for platelet activity (ie, platelet factor-4 and beta-thromboglobulin [TG]), thrombotic status (ie, prothombin fragments 1 and 2), and fibrinolytic status (ie, d-dimer) were determined in 246 patients with NVAF (mean age, 66.1 years) and 111 control subjects without NVAF (68.3 years). The beta-TG level was higher in NVAF patients than in control subjects. D-dimer levels were higher in NVAF patients having risk factors (mean [+/- SE] d-dimer level, 158.6 +/- 9.2 ng/mL) than in those without risk factors (mean d-dimer level, 92.1 +/- 6.7 ng/mL; p < 0.01) and in control subjects (mean d-dimer level: control subjects with risk factors, 79.1 +/- 10.3 ng/mL; control subjects without risk factors, 31.0 +/- 7.4 ng/mL; p < 0.01). NVAF (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.87 to 8.30; p = 0.0003) and age of >/= 75 years (OR, 5.68; 95% CI, 2.87 to 11.23; p < 0.0001) emerged as predictors of elevated levels of d-dimer, and only NVAF (OR, 10.30; 95% CI, 5.67 to 18.72; p < 0.0001) emerged as a predictor of elevated levels of beta-TG. NVAF patients whose conditions were complicated with risk factors for embolism could be in the prothrombotic state. Advanced age is a strong predictor of the prothrombotic state in NVAF patients.

Predictors of In-Hospital Mortality and Attributable Risks of Death After Ischemic Stroke: The German Stroke Registers Study Group

Article

Sep 2004
ARCH INTERN MED

There is a lack of information about factors associated with in-hospital death and the impact of neurological complications on early outcome for patients with stroke treated in community settings. We investigated predictors for in-hospital mortality and attributable risks of death after ischemic stroke in a pooled analysis of large German stroke registers. Stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000, and December 31, 2000, were analyzed. The ADSR is a network of regional stroke registers, combining data from 104 academic and community hospitals throughout Germany. The impact of patients' demographic and clinical characteristics, their comorbid conditions, and the treating hospital expertise in stroke care on in-hospital mortality was analyzed using Cox regression analysis. Attributable risks of death for medical and neurological complications were calculated. A total of 13 440 ischemic stroke patients were included. Overall in-hospital mortality was 4.9%. In women, higher age (P<.001), severity of stroke defined by number of neurological deficits (P<.001), and atrial fibrillation (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.0-1.6) were independent predictors for in-hospital death. In men, diabetes (HR, 1.3; 95% CI, 1.0-1.8) and previous stroke (HR 1.4; 95% CI, 1.0-1.9) had a significant negative impact on early outcome in addition to the factors identified for women. The complication with the highest attributable risk proportion was increased intracranial pressure, accounting for 94% (95% CI, 93.9%-94.1%) of deaths among patients with this complication. Pneumonia was the complication with the highest attributable proportion of death in the entire stroke population, accounting for 31.2% (95% CI, 30.9%-31.5%) of all deaths. More than 50% of all in-hospital deaths were caused by serious medical or neurological complications (54.4%; 95% CI, 54.3%-54.5%). Substantial differences were found in the impact of comorbid conditions on early outcome for men and women. Programs aiming at an improvement in short-term outcome after stroke should focus especially on a reduction of pneumonia and an early treatment of increased intracranial pressure.

Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction

Article

May 2005
J CLIN NEUROSCI

We investigated the plasma levels of D-dimer, fibrinogen, beta-thromboglobulin (BTG) and platelet factor-4 (PF-4), indices of the occurrence of platelet activation in vivo, to find out their role in pathophysiology of ischemic stroke and whether or not such a role has any effect on the disability and the prognosis of stroke patients. A total of 76 patients with AIS aged from 26 to 85 (32 men, 44 women) and 30 cases as controls with similar age (18 men, 12 women) were included in the study. The plasma levels of D-dimer, BTG and PF-4 were measured by ELISA method using a special commercial kit. The cases were allocated into two groups as non-embolic (NEI) and cardioembolic stroke (CEI). The D-dimer levels in 76% of 42 patients in NEI group (p<0.05) and 85.2% of 34 patients in CEI group (p<0.05) were outside the confidence interval (CI) defined for the control group. The levels of BTG were elevated in 81% of 42 cases with NEI (p<0.05) and in 76% of 34 cases with CEI, with reference to CI of control group. The levels of PF-4 were significantly increased in 86% of cases with NEI (p<0.05) and in 88% of cases with CEI than controls (p<0.05). It was observed that the cases with high Rankin scores had higher levels of D-dimer (p<0.005), BTG (p<0.01) and PF-4 (p<0.01) than those with lower scores. There was a correlation between hemostatic markers, platelet activation and functional disability. D-dimer levels were an important marker that determined to degree of the activation of hemostatic system, especially in CEI subtype. The platelet aggregation had an important role in pathophysiology of ischemic stroke and this condition is significant in NEI subgroup and subjects with large infarcts and high disability scores.

D-dimer level influences thromboembolic events in patients with atrial fibrillation

Article

Apr 2006
INT J CARDIOL

Elevated coagulative molecular markers could reflect the prothrombotic state in the cardiovascular system of patients with non-valvular atrial fibrillation (NVAF). A prospective, cooperative study was conducted to determine whether levels of coagulative markers alone or in combination with clinical risk factors could predict subsequent thromboembolic events in patients with NVAF. Coagulative markers of prothrombin fragment 1+2, D-dimer, platelet factor 4, and beta-thromboglobulin were determined at the enrollment in the prospective study. Of 509 patients with NVAF (mean age, 66.6 +/- 10.3 years), 263 patients were treated with warfarin (mean international normalized ratio, 1.86), and 163 patients, with antiplatelet drugs. During an average follow-up period of 2.0 years, 31 thromboembolic events occurred. Event-free survival was significantly better in patients with D-dimer level < 150 ng/ml than in those with D-dimer level>or==150 ng/ml. Other coagulative markers, however, did not predict thromboembolic events. Age (>or==75 years), cardiomyopathies, and prior stroke or transient ischemic attack were independent, clinical risk factors for thromboembolism. Thromboembolic risk in patients without the clinical risk factors was quite low (0.7%/year) when D-dimer was < 150 ng/ml, but not low (3.8%/year) when D-dimer was >or==150 ng/ml. It was >5%/year in patients with the risk factors regardless of D-dimer levels. This was also true when analyses were confined to patients treated with warfarin. D-dimer level in combination with clinical risk factors could effectively predict subsequent thromboembolic events in patients with NVAF even when treated with warfarin.

D-Dimer Predicts Early Clinical Progression in Ischemic Stroke: Confirmation Using Routine Clinical Assays

Article

May 2006
STROKE

Plasma d-dimer levels, measured using a research laboratory assay, independently predict progressing ischemic stroke. We wished to confirm these findings using commercially available assays and to provide data to allow the design of intervention studies. We studied 219 consecutive acute ischemic stroke admissions of whom 54 (25%) met criteria for progressing stroke. There were strong correlations between d-dimer results as measured by the Biopool AB, MDA and VIDAS assays; correlation coefficients r=0.91 to 0.94; all P<0.001. In binary logistic regression analyses, d-dimer, as measured by the 3 different assays, was an independent predictor of progressing stroke (odds ratios, 1.87 to 2.45; all P<0.001). This confirms the results of our original analysis (Biopool AB) using 2 commercial d-dimer assays, demonstrating the potential usefulness of d-dimer in providing early prognostic information after ischemic stroke in different clinical settings. We also provide information on the performance of the 3 assays in predicting progressing stroke at a variety of cutoff values. Ischemic stroke patients at high risk of early progression can be identified using commercial d-dimer measurements. This could allow selection of high-risk patients for inclusion in randomized trials of early antithrombotic treatments.

D-dimer is not a long-term prognostic marker following acute cerebral ischemia

Article

Jul 2006

Recent evidence indicates a possible role of D-dimer in the early diagnosis of ischemic stroke subtypes. Whether D-dimer can also predict the long-term outcome following ischemic stroke is controversial. To define the prognostic role of D-dimer, patients hospitalized after an acute ischemic cerebrovascular event underwent D-dimer measurement (Liatest D-D; normal level < 0.50 microg/ml) on admission and were followed up for recurrent cerebrovascular events, occurrence of other cardiovascular events, and mortality. We enrolled 96 patients (mean age 74.9 years, 42 men). Mean follow-up was 61.5 months; 47 (48.5%) patients died, 23 (48.9%) because of a vascular event. There was no difference in mean D-dimer levels between dead patients and survivors (1.68 and 1.63 microg/ml, P = NS), but the mortality risk was higher with D-dimer of at least 0.50 microg/ml (odds ratio, 5.32; 95% confidence interval, 1.79-15.84). After adjustment for age and stroke subtype, the odds ratio was not significant. Mean D-dimer was similar between patients with and without a new vascular event (1.43 and 1.68 microg/ml, P = NS), and D-dimer of at least 0.50 microg/ml was not predictive of an increased risk of subsequent events. D-dimer levels measured in the acute phase after an acute cerebrovascular event probably do not predict the long-term clinical outcome.

Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study

Article

Sep 2006
LANCET NEUROL

Background: Vitamin K antagonists (eg, warfarin) substantially reduce the risk of ischaemic stroke in patients with atrial fibrillation. Additionally, therapeutic anticoagulation at time of acute stroke admission might reduce in-hospital mortality and disability. We assessed the association between preadmission antithrombotic treatment and initial stroke severity, neurological deterioration, major vascular events during hospital stay, and death or disability at discharge in patients with acute ischaemic stroke and atrial fibrillation. Methods: We identified consecutive patients with acute ischaemic stroke and atrial fibrillation, admitted to 11 hospitals in Ontario, Canada, from the Registry of the Canadian Stroke Network (2003-05). Logistic regression was used to assess the association between antiplatelet treatment, subtherapeutic warfarin treatment (admission international normalised ratio [INR] < 2), therapeutic warfarin treatment (admission INR > or = 2), and clinical outcome. Stroke severity was measured using the Canadian neurological scale (CNS) and was categorised into mild (CNS > 7) and severe stroke (CNS < or = 7). Disability was measured with the modified-Rankin scale (mRS) and was categorised into strokes associated with no or mild-moderate dependency (mRS 0-3) and with severe dependency or death (mRS 4-6). Results: Of 948 patients, 306 (32%) were not on antithrombotic treatment, 292 (31%) were receiving antiplatelet treatment, 238 (25%) were receiving warfarin with a subtherapeutic INR, and 112 (12%) were receiving warfarin with a therapeutic INR on admission. Compared with those not receiving antithrombotic therapy, antiplatelet therapy (odds ratio 0.7; 95% CI 0.5-0.995) and therapeutic warfarin (0.4; 0.2-0.6) were associated with a reduction in severe stroke at admission. Therapeutic warfarin was also associated with a reduction in the odds of severe disability or death at discharge (0.5; 0.3-0.9). Interpretation: Therapeutic warfarin is associated with reduced severity of ischaemic stroke at presentation and reduced disability or death at discharge in patients with atrial fibrillation. Antiplatelet treatment is associated with a more modest reduction than warfarin in baseline stroke severity.

Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation

Article

Jun 2008

The present study was conducted to investigate the relation between the accumulation of the risk factors of thromboembolism and the levels of hemostatic markers in patients with nonvalvular atrial fibrillation (NVAF). Five hundred ninety-one NVAF patients and 129 control subjects were categorized into low, moderate or high risk of thromboembolism, according to CHADS(2) index. One point each was given to patients with advanced age (> or =75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with CHADS(2) score of 0, 1 or 2, and > or =3 were classified as low, moderate and high risk, respectively. Levels of hemostatic markers (platelet factor 4, beta-thromboglobulin, prothrombin fragment F1+2 and D-dimer) were determined. Of 591 patients with NVAF, 302 were treated with warfarin (mean international normalized ratio 1.88). D-dimer levels increased as the risk level increased irrespective of warfarin use. Particularly, NVAF patients without receiving warfarin (n=289) had significantly higher D-dimer levels than control patients (e.g., for high risk patients, 175+/-144 vs 75+/-87 ng/ml, p<0.001), while NVAF patients receiving warfarin had intermediate levels (136+/-156 ng/ml). F1+2 levels increased as the risk level increased, and were significantly suppressed by warfarin. Levels of markers of platelet activation (platelet factor 4 and beta-thromboglobulin) were increased in NVAF patients but not affected by the risk level. Coagulation and fibrinolytic activity is increased along with the accumulation of the risk factors of thromboembolism in NVAF patients.

High D-dimer level is associated with increased 15-d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity

Article

Apr 2008
BRIT J HAEMATOL

High D-dimer levels are predictors of death in patients with pulmonary embolism (PE), as are more proximally located, larger emboli. The direct link between these three has not yet been described. A cohort of 674 consecutive patients with confirmed PE was studied. Patients were followed up for 3 months. D-dimer levels were measured only in patients with an unlikely clinical probability (n = 262). The odds ratio (OR) for death of all variables was calculated. Multivariate analysis was performed to identify independent risk factors for mortality. The best predictive D-dimer cut-off point for mortality was a concentration >3000 ng/ml FEU (OR 7.29). High D-dimer levels were correlated with active malignancy and age over 65 years, both being indicators of 3-month mortality. High D-dimer levels were also correlated with centrally located pulmonary emboli and 15-d mortality. The combination of high D-dimer levels and central emboli increased early mortality risk by 2.2. High D-dimer levels in patients with an unlikely clinical probability were associated with fatal outcome after PE. Centrally located pulmonary emboli were associated with higher D-dimer levels and worse 15-d mortality. Active malignancy, being an inpatient at time of diagnosis and age over 65 years were associated with higher D-dimer levels and worse 3-month survival.

Relationship between Plasma D-Dimer Level and Cerebral Infarction Volume in Patients with Nonvalvular Atrial Fibrillation

Abstract

No full-text available

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