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D-Dimer Levels, Stroke, and Critical Care
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This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), d -dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, d -dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, d -dimer, and FDP than the controls ( P < 0.01). Plasma FIB, d -dimer, and FDP were also increased in active groups of RA patients than those in inactive groups ( P < 0.001). ROC curve analyses revealed that the AUC of d -dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, d -dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, d -dimer, and FDP were positively related with DAS28-CRP ( P < 0.001) in RA patients. Logistical regression analysis showed that d -dimer (odds ratio 2.862, 95% confidence interval 1.851–5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, d -dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. d -dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.
Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy, and D-dimer levels have been used to predict disease severity. However, the role of D-dimer in predicting mortality in COVID-19 patients with acute ischemic stroke (AIS) remains incompletely characterized.
Methods: We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record dataset. Patients were included if they were 18 or older, had been hospitalized within 7 days of confirmed COVID-19 positivity from March 1, 2020 to November 30, 2020. We determined the optimal threshold of D-dimer to predict in-hospital mortality and compared risks of in-hospital mortality between patients with D-dimer levels below and above the cutoff. Risk ratios (RRs) were estimated adjusting for baseline characteristics and clinical variables.
Results: Among 15,250 patients hospitalized with COVID-19 positivity, 285 presented with AIS at admission (2%). Patients with AIS were older [70 (60–79) vs. 64 (52–75), p < 0.001] and had greater D-dimer levels at admission [1.42 (0.76–3.96) vs. 0.94 (0.55–1.81) μg/ml FEU, p < 0.001]. Peak D-dimer level was a good predictor of in-hospital mortality among all patients [c-statistic 0.774 (95% CI 0.764–0.784)] and among patients with AIS [c-statistic 0.751 (95% CI 0.691–0.810)]. Among AIS patients, the optimum cutoff was identified at 5.15 μg/ml FEU with 73% sensitivity and 69% specificity. Elevated peak D-dimer level above this cut-off was associated with almost 3 times increased mortality [adjusted RR 2.89 (95% CI 1.87–4.47), p < 0.001].
Conclusions: COVID-19 patients with AIS present with greater D-dimer levels. Thresholds for outcomes prognostication should be higher in this population.
Background
Pneumonia is related to poor prognosis in acute ischemic stroke (AIS), and its risk might be higher in atrial fibrillation (AF) related AIS with elevated plasma D-dimer. The aim of our study was to investigate the prognostic value of D-dimer for predicting clinical outcome of AF-related AIS with pneumonia.
Method
AF-related AIS patients with pneumonia were prospectively enrolled. Receiver operating characteristic (ROC) curve was used to determine the optimal D-dimer point for 3-month mortality and death/severe disability. The associations between the D-dimer and 3-month mortality and death/severe disability were assessed by multivariable logistic regression analysis.
Results
A total of 415 patients were enrolled in this study. ROC curve analysis showed that the optimal cut point of D-dimer for 3-month death/severe disability and mortality were D-dimer≥2.35 mg/l and D-dimer≥3.35 mg/l, respectively. Multivariable logistic regression analysis showed that D-dimer≥2.35 mg/l [adjusted odds ratio (aOR) 5.99, 95% confidence interval (CI): 3.04–11.83, P<0.001], higher NIHISS score (aOR:1.53, 95% CI: 1.38–1.69, P<0.001) and larger infarct volume (aOR 1.01, 95% CI: 1.01–1.02, P<0.001) were associated with increased risk of 3-month death/severe disability), and anticoagulant was associated with decreased risk of death/severe disability (aOR:0.21, 95% CI: 0.09–0.47, P<0.001). Higher NIHISS score (aOR:1.64, 95% CI: 1.38–1.94, P<0.001), older age (aOR 1.08, 95% CI: 1.02–1.14, P = 0.007), D-dimer≥3.35 mg/l (OR 8.49, 95% CI: 4.13–17.84,P<0.001), larger infarct volume (aOR 1.02, 95% CI: 1.00–1.03, P = 0.014), and higher CRUB-65 score (aOR 6.43, 95% CI: 3.10–13.34, P<0.001) were associated with increased risk of 3-month mortality.
Conclusions
AF-related AIS patients with concurrent high D-dimer and pneumonia increased risk of 3-month mortality and death/severe disability, plasma D-dimer may have predictive value in outcome after AF-related AIS with pneumonia.
Background
Biological markers of acute nerve cell damage can assist in the outcome of acute ischemic stroke, such as neuron-specific enolase (NSE) that have been tested for association with initial severity of stroke, extent of infarction, and functional outcome.
Objective
To determine short-term prognostic value of the biochemical marker neuron-specific enolase (NSE) in acute ischemic stroke.
Methods
A cohort study carried out on 37 patients with acute ischemic stroke. Data were gathered in a prepared data sheet. Initial serum NSE level was measured to the patients in the Emergency department within 6 h of the onset of stroke and another measurement after 48 h. National Institute of Health Stroke Scale (NIHSS) was held to the patients at presentation and after 28 days of stroke to determine short-term morbidity and mortality.
Results
Out of the 37 patients, 31 patients survived (no-death group) and 6 patients died (death group). The mean serum level of neuron-specific enolase at presentation and after 48 h was significantly higher in the death group than in the no-death group. There was a statistically significant positive correlation between neuron-specific enolase (NSE) serum level and clinical severity of stroke (NIHSS) among the patients at presentation ( r = 0.737, p = 0.000).
Conclusion
Neuron-specific enolase (NSE) can be applied as single independent marker for prediction of mortality and short-term morbidity in ischemic stroke patients.
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.
Stroke continues to be the third-leading cause of death and disability worldwide. The limited availability of diagnostic tools approved therapeutics and biomarkers that help monitor disease progression or predict future events remain as the major challenges in the field of stroke medicine. Hence, attempts to discover safe and efficacious therapeutics and reliable biomarkers are of paramount importance. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. Since miRNAs also play important roles in key mechanisms associated with the pathogenesis of stroke, including energy failure, inflammation and cell death, it is possible that miRNAs may serve as reliable blood-based markers for risk prediction, diagnosis and prognosis of ischaemic stroke. Discovery of better neurological outcome and smaller cerebral infarcts in animal models of ischaemic stroke treated with miRNA agomirs or antagomirs indicate that miRNAs may also play a cerebrovascular protective role after an ischaemic stroke. Nonetheless, further evidences on the optimum time for treatment and route of administration are required before effective translation of these findings into clinical practice. Bearing these in mind, this paper reviews the current literature discussing the involvement of miRNAs in major pathologies associated with ischaemic stroke and evaluates their value as reliable biomarkers and therapeutics for ischaemic stroke.
D-dimer is a biomarker of thrombosis and recently been considered to predict a poor outcome in patients with infectious diseases. Plasma D-dimer levels were measured in critically ill patients to examine their relationship with the poor outcome. The plasma D-dimer levels were markedly higher in the patients with various underlying disease especially venous thromboembolism in comparison to those without severe underlying diseases. The plasma D-dimer levels in non-survivors were significantly higher than those in survivors. In a receiver operating characteristic analysis, the area under the curve was high for the disseminated intravascular coagulation (DIC) score, the D-dimer value, and the prothrombin time-international normalize ratio (PT-INR). Adequate cut-off values for predicting the outcome were 3 as follows: DIC score, 3 points; D-dimer, 4.2 mg/L; and PT-INR, 1.08. D-dimer, which is a biomarker for thrombosis, is increased in various underlying diseases and predicts a poor outcome.
Venous thromboembolism (VTE) is regarded as a significant cause of mortality and disability, affecting 1–2 per 1000 people annually, presenting with a relatively wide range of symptoms, which can pose a diagnostic challenge. Historically, people in whom VTE is suspected will have been taken to hospital for diagnosis and treatment; however, a high proportion of patients are found not to have VTE. Concerns have been expressed about potential delays in treatment, with the risk of additional morbidity and disability, and death. Diagnostic strategies are typically based on the use of a clinical prediction rule to determine the pre-test probability, complemented with a measurement of D-dimer, with confirmation by imaging assessment. This narrative review explores the literature on the use of point-of-care testing (POCT) for the measurement of D-dimer, as part of a clinical decision rule, for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the primary care setting. In the two main prospective management (validation) studies that included D-dimer POCT or similar technologies, with a total cohort of 1600 participants, DVT was ruled out in 49% of patients, with a false negative rate of 1.4%, whereas PE was ruled out in 45% of patients, with a false negative rate of 1.5%. This suggests that uptake of POCT D-dimer in primary care has the potential to reduce the number of referrals to hospitals for imaging confirmatory investigation, with consequent cost savings. Thus, adopting POCT for D-dimer in primary care can offer clinical and cost benefits, particularly when quantitative POCT assays are being used. Furthermore, POCT should be undertaken in collaboration with the local laboratories to ensure the harmonisation of D-dimer methods and quality assurance to improve the diagnosis of VTE.
Abstract Background Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS). Methods This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models. Results This study included 4274 patients (median age 68 years [interquartile ranges {IQR}: 61–76]; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P
Background:
Over 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome.
Methods:
We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with in-hospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization.
Results:
Multivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10-94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall's tau-b = 0.374, P = 0.000) and chest CT staging (Kendall's tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79-16.01) mg/L versus 1.02 (0.47-2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77-0.92).
Conclusions:
D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.
Background:
In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern.
Objectives:
To describe the coagulation feature of patients with NCP.
Methods:
Conventional coagulation results and outcomes of consecutive 183 patients with confirmed NCP in Tongji hospital were retrospectively analysed.
Results:
The overall mortality was 11.5%, the non-survivors revealed significantly higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P<0.05). 71.4% of non-survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay.
Conclusions:
The present study shows that abnormal coagulation results, especially markedly elevated D-dimer and FDP are common in deaths with NCP.
Importance
In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
Objective
To describe the epidemiological and clinical characteristics of NCIP.
Design, Setting, and Participants
Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.
Exposures
Documented NCIP.
Main Outcomes and Measures
Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.
Results
Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).
Conclusions and Relevance
In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
Background
High levels of inflammatory markers such as C-reactive protein (CRP) and interleukin (IL)-6 are associated with worse outcome after ischemic stroke.
Objectives
To study whether the level of IL-6 following ischemic stroke is related to the severity of stroke, infarct volume, stroke subtype, and its impact on stroke outcome.
Materials and methods
A total of 90 patients of acute ischemic stroke were enrolled with calculation of infarct volume in MRI brain, and serum IL-6 samples were obtained within 24 h and also after 3 months from stroke onset. NIHSS and MRS were done at stroke onset and after 3 months.
Results
The mean value of IL-6 was higher among patients with small vessel occlusion (8.47 pg/ml) with a significant positive correlation between IL-6 and National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (MRS) after 3 months. IL-6 was significantly higher in patients with recurrence with a cutoff IL-6 value above which recurrence is anticipated which is 7.75 pg/ml.
Conclusion
Our study concluded that inflammation has an important role in the pathogenesis of acute ischemic stroke particularly small vessel occlusion and it provided evidence that IL-6 contributes to the determination of clinical outcome of acute ischemic stroke and prediction of recurrence.
Background
The apolipoprotein A1 level is recognized as a better indicator of cardiovascular disease than other cholesterol measures.
Objectives
To assess the serum level of ApoA1 in acute stroke patients and correlate it with the degree of vessel stenosis, stroke severity, prognosis, and functional outcome.
Patients and methods
We prospectively included 60 patients with first-ever cerebrovascular ischemic stroke, and they were matched with 30 healthy individuals matched in age and sex. Patients’ neurological status was assessed via National Institute of Health and Stroke Scale (NIHSS). A venous blood sample was taken within the first 24 h of stroke onset and assayed for ApoA1 level by Human ApoA1 ELISA kit.
Results
ApoA1 level could be used to discriminate between cases and controls at a level of 6.2 μg/ml, with 94.9% sensitivity and 86.6% specificity. Furthermore, there is an inverse relationship between the level of ApoA1 and the clinical outcome expressed by NIHSS score and their prognosis after 3 months. Finally, there is an inverse relationship between ApoA1 level and the degree of stenosis whether intracranial or extracranial.
Conclusion
ApoA1 level can be used as a predictor of ischemic stroke and as a prognostic tool for those patients with ischemic stroke.
Background
Elevated CRP and increased CCA-IMT are both associated with the occurrence of stroke. CRP and IMT are closely associated; the higher the CRP, the greater the carotid atherosclerosis as measured by carotid IMT.
Objectives
To study the relationship between elevated C-reactive protein as a blood biomarker and increased intimal media thickness of carotid artery, and its relation to infarct size and its impact on prognosis.
Materials and methods
This study is an analytical observational study, in which 73 patients who have recently suffered first-ever acute ischemic stroke in the anterior circulation within 72 h were recruited. Only 64 of them were able to continue the study with follow-up during the 1 month and 3 months durations. Magnetic resonance imaging for the brain was done and the infarct volume was measured. All patients had quantitative Serum CRP level within 72 h from stroke onset and carotid duplex with assessment of carotid intimal media thickness (IMT).
Results
The results showed there is a significant positive correlation between highly sensitive C-reactive protein (hs-CRP) and MRS after 1 month yet no significant correlation was found between hs-CRP and IMT.
Conclusion
Highly sensitive C-reactive protein (hs-CRP) could serve as prognostic blood biomarker in long-term follow-up of stroke patients. Non-significant correlation was found in our study between increased hs-CRP and increased intima-media thickness (CCA-IMT).
Background
The brain is a productive source of a variety of enzymes and any brain injury like a stroke to brain tissue could similarly result in an increase in these enzymes in cerebrospinal fluid and serum. Evaluation of these enzymes represents a simple method for the ischemic stroke subtype diagnosis and prognosis. Objective : This study aimed to determine the role of brain natriuretic peptide (BNP), d -dimer, creatine–kinase-MB (CK-MB), C-reactive protein (CRP) serum levels, and globulin/albumin ratio in the diagnosis of CES stroke and its ability to predict short-term outcome.
Methods
This study was conducted on 96 patients with acute ischemic stroke, subdivided into two groups: group Ι was 48 patients with cardio-embolic stroke and group ΙΙ was 48 patients with non-cardio-embolic. All patients were subjected to the assessment of serum BNP, d -dimer and CK-MB, and CRP and globulin/albumin ratio within the first 24 h of stroke. In the third week, they were assessed by mRS.
Results
The mean levels of BNP, d -dimer level, and CK-MB were significantly higher in patients with cardio-embolic stroke than in patients with non-cardio-embolic stroke ( P < 0.001) and also were associated with poor short-term outcome.
Conclusion
Elevated plasma levels of BNP, d -dimer levels, and CK-MB can be used as surrogate biomarkers for the diagnosis of cardio-embolic stroke and prediction of poor short-term outcomes.
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.
A modern diagnostic laboratory offers wide spectrum of coagulation assays utilized in the diagnosis and management of patients with haemostatic disorders, preoperative screening and anticoagulation therapy monitoring. The recent survey conducted among Croatian medical biochemistry and transfusion laboratories showed the existence of different practice policies in particular phases of laboratory process during coagulation testing and highlighted areas that need improvement. Lack of assay standardization together with non-harmonized test results between different measurement methods, can potentially lead to incorrect decisions in patient's treatment. Consequently, patient safety could be compromised. Therefore, recommended procedures related to preanalytical, analytical and postanalytical phases of prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen and D-dimer testing are provided in this review, aiming to help laboratories to generate accurate and reliable test results.
D-dimer is a soluble fibrin degradation product deriving from the plasmin-mediated degradation of cross-linked fibrin. D-dimer can hence be considered a biomarker of activation of coagulation and fibrinolysis, and it is routinely used for ruling out venous thromboembolism (VTE). D-dimer is increasingly used to assess the risk of VTE recurrence and to help define the optimal duration of anticoagulation treatment in patients with VTE, for diagnosing disseminated intravascular coagulation, and for screening medical patients at increased risk of VTE. This review is aimed at (1) revising the definition of D-dimer; (2) discussing preanalytical variables affecting the measurement of D-dimer; (3) reviewing and comparing assay performance and some postanalytical variables (e.g. different units and age-adjusted cutoffs); and (4) discussing the use of D-dimer measurement across different clinical settings.
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.
Background: According to recent studies, brain-derived neurotrophic factor (BDNF) probably plays a role in development of cerebral ischemia and can be significant for the prognosis of improved mobility after stroke. The aim of this prospective study was to evaluate the blood concentration of BDNF during the 1 st day of first-ever ischemic stroke and find a potential association between BDNF concentration and the neurological status in the acute period, as well as between BDNF and the functional status in the sub-acute phase of stroke. Material/Methods: The prospective study involved 87 patients aged 39–99 years (42 women, 45 men) with first-in-life complete ischemic stroke. All study subjects underwent analysis as follows: BDNF blood concentration and neurological status according to NIHSS on the 1 st day of stroke, comorbidities, etiological type of ischemic stroke by ASCOD, and functional status on the 14 th and 90 th day after the onset according to mRankin scale. Results: Mean concentration of BDNF in the study group was 9.96 ng/mL±5.21, median 10.39 ng/mL. Patients aged £65 years (25 individuals) had a significantly higher mean concentration of BDNF (11.94 ng/mL±4.46; median 12.34 ng/mL) than the older subjects (62 individuals) with a mean concentration of 9.17 ng/mL±5.32 (median 8.66 ng/mL). The mean score by mRankin scale on the 90 th day was significantly higher among patients with lower concentrations of BDNF on the 1 st day of stroke, which reflects their poorer functional status. The functional status on the 90 th day was significantly worse (3–6 points by Rankin scale) in patients who had BDNF below the mean value in the acute phase of stroke. The independent factors for poor functional status of patients on the 90 th day after stroke were a score >4 points by NIHSS (RR 1.14; 95% CI: 1.00–1.31; p=0.027) and the concentration of BDNF below the mean value (assessed on the 1 st day of stroke) (RR 14.49; CI 4.60–45.45; p=0.000). Conclusions: The neurological status and concentration of BDNF on the 1 st day of ischemic stroke are independent prognos-tic factors in medium-term observation. Reduction in the concentration of BDNF in the acute phase of stroke is a factor for poor prognosis in terms of the functional status of patients on the 90 th day after onset.
D-dimer is the biochemical gold standard for diagnosing a variety of thrombotic disorders, but result reporting is heterogeneous in clinical laboratories. A specific five-item questionnaire was developed to gain a clear picture of the current standardization of D-dimer test results. The questionnaire was opened online (December 24, 2014-February 10, 2015) on the platform "Google Drive (Google Inc., Mountain View; CA)," and widely disseminated worldwide by newsletters and alerts. A total of 409 responses were obtained during the period of data capture, the largest of which were from Italy (136; 33%), Australia (55; 22%), Croatia (29; 7%), Serbia (26; 6%), and the United States (21; 5%). Most respondents belonged to laboratories in general hospitals (208; 51%), followed by laboratories in university hospitals (104; 26%), and the private sector (94; 23%). The majority of respondents (i.e., 246; 60%) indicated the use of fibrinogen equivalent unit for expressing D-dimer results, with significant heterogeneities across countries and health care settings. The highest prevalence of laboratories indicated they were using "ng/mL" (139; 34%), followed by "mg/L" (136; 33%), and "µg/L" (73; 18%), with significant heterogeneity across countries but not among different health care settings. Expectedly, the vast majority of laboratories (379; 93%) declared to be using a fixed cutoff rather than an age-adjusted threshold, with no significant heterogeneity across countries and health care settings. The results of this survey attest that at least 28 different combinations of measurement units are currently used to report D-dimer results worldwide, and this evidence underscores the urgent need for more effective international joined efforts aimed to promote a worldwide standardization of D-dimer results reporting.
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Inflammatory markers are being explored to aid in stroke diagnosis especially, to differentiate between clinical varieties of stroke. This study aimed to compare plasma tumour necrosis factor-alpha (TNF-alpha) and Interleukin-10 (IL-10) levels between stroke patients and controls, as well as between hemorrhagic and ischemic varieties of stroke.
Stroke patients who were admitted to Shaikh Zayed Hospital Lahore and Services Hospital Lahore, Pakistan within 24 hours after the onset of stroke symptoms were consecutively asked to participate in this study from June 2011 to December 2011.Venous blood samples were collected within 24 hours of stroke symptoms onset. Plasma TNF-α levels and IL-10 were calculated using commercial enzyme-linked immune-sorbent assay (ELISA). Cytokines levels were dichotomized as detectable yes/no and were compared between different groups using chi square test. Continuous variables were compared using the student t-test. Logistic regression model was used to investigate the effect of various risk factors on stroke subtypes. A value of p < 0.05 was considered significant.
One hundred and thirty one stroke patients were included in the study, out of which 93 were ischemic and 38 were haemorrhagic stroke patients. Forty-seven healthy asymptomatic individuals were included .as controls Plasma TNF-α levels (p < 0.001, r = 0.503, CI: 18.197-1672.950) were significantly elevated in stroke patients as compared to controls, along with advancing age (p = 0.002, r = 0.310, CI: 1.025-1.110) and history of hypertension (p = 0.002, r = 0.265, CI: 1.746-12.511). Males were found to be at a higher risk of developing stroke. Furthermore, history of hypertension (p=0.019, r= -0.294, CI: 0.134-1.500) and detectable TNF- levels (p = 0.002, r = 0.319, CI: 2.106-23.725) were found to be significantly different between ischemic and haemorrhagic stroke patients.
TNF-α level differed highly significantly between stroke and controls, and also between ischemic and haemorrhagic stroke subtypes.
Serum biomarkers are becoming increasingly important in the assessment of patients with ischemic stroke. In this paper we perform an updated review of serum biomarkers in the assessment of ischemic stroke, with special interest on molecular markers associated with vascular risk, both in primary and secondary prevention, stroke diagnosis and the presence of neurological deterioration, infarct volume, hemorrhagic transformation, arterial recanalization and other prognostic variables. We also review the role of molecular markers during the acute phase of stroke. The knowledge of these serum biomarkers is important to improve functional outcome and to develop new therapeutic strategies in patients with ischemic stroke. Copyright © 2012 Prous Science, S.A.U. or its licensors. All rights reserved.
This review provides a summary of the protein and RNA biomarkers that have been studied for the diagnosis and assessment of ischemic stroke. Many of the biomarkers identified relate to the pathophysiology of ischemic stroke, including ischemia of CNS tissue, acute thrombosis and inflammatory response. These biomarkers are summarized by their intended clinical application in ischemic stroke including diagnosis, prediction of stroke severity and outcome, and stratification of patients for stroke therapy. Among the biomarkers discussed are recent whole genome studies using RNA expression profiles to diagnose ischemic stroke and stroke etiology. Though many candidate blood based biomarkers for ischemic stroke have been identified, none are currently used in clinical practice. With further well designed study and careful validation, the development of blood biomarkers to improve the care of patients with ischemic stroke may be achieved.
Quantitation of D-dimer level during a sickling crisis and its correlation with other clinical abnormalities.Design: Prospective longitudinal study.
Armed Forces Hospital, Southern Region, Kingdom of Saudi Arabia.
Adult patients (12 years and older) admitted acutely with a sickle cell crisis who consent to taking part in the study. Candidates may re-participate if they are readmitted with a further acute painful crisis.
36 patients with homozygous sickle cell disease consented to take part in the study. D-dimer levels were raised in 31 (68.9%) of 45 episodes of painful crisis of whom 13 had an abnormal chest X-ray. Of those with a normal chest X-ray only one patient had a raised D-dimer level: sensitivity of 92.3%, specificity 40.6%, positive predictive value 38.7% and negative predictive value of 92.9% for an abnormal chest X-ray.
D-dimer levels are frequently raised during an acute painful crisis. A normal level has a high negative predictive value for an abnormal chest X-ray.
Objective:
Plasma D-dimer levels greater than 5,000 ng/ml are encountered in a number of conditions beyond venous thromboembolism (VTE). Recent studies have used plasma D-dimer levels as a prognostic indicator for COVID-19 infection. The implications of abnormal levels are less clear for COVID-positive patients with baseline elevation in plasma D-dimer levels. This study reviews the occurrence of plasma D-dimer levels >5,000 ng/ml and investigates the clinical significance of this finding prior to the onset of the COVID-19 pandemic.
Methods:
Inpatient records over a four-year period were screened for laboratory results of plasma D-dimer levels >5,000 ng/ml. Patient data was reviewed for clinical identifiers commonly associated with elevated plasma D-dimer levels, which included VTE, cancer, sepsis, pneumonia, other infection, bleeding, and trauma. Patients were then categorized into groups by plasma D-dimer level to allow comparison between the various clinical diagnoses.
Results:
A total of 671 patients were included in the study. VTE was the most common diagnosis in patients with a plasma D-dimer level >5000 ng/ml followed by cancer and pneumonia. Multiple clinical diagnoses were present in 61% of patients. No clear cause for the ultra-high plasma D-dimer level could be identified in 11.3% of patients. Among the patients lacking a clinical diagnosis at the time of discharge, mortality was 24% in the 5,000-10,000 ng/ml group, 28.6% in the 10,000-15,000 ng/ml group, and 75% in the >15,000 ng/ml group.
Conclusions:
VTE, cancer, and pneumonia are frequently present when ultra-high plasma D-dimer levels are encountered, and mortality is high when levels exceed 15,000 ng/ml. The results of our study from a pre-COVID-19 patient population suggest that ultra-high plasma D-dimer levels indicate the presence of severe underlying disease. This should be considered when using plasma D-dimer as a screening tool or prognostic indicator for COVID-19 infection.
Funding Acknowledgements
Type of funding sources: None.
Background
Ruling out pulmonary embolism (PE) through a combination of clinical assessment and Ddimer is crucial to avoid excessive computed tomography pulmonary angiography (CTPA), and different algorithms should be considered as an alternative to the fixed cutoff to achieve that goal.
Purpose
To compare sensitivity, specificity, and reduction in CTPA requests of 4 algorithms to rule out PE: fixed Ddimer cutoff, age-adjusted, YEARS and PEGeD.
Methods
Retrospective study of consecutive outpatients who presented to the emergency department and underwent CTPA for PE suspicion from April 2019 to February 2020. The clinical-decision algorithms were retrospectively applied.
In fixed and age-adjusted cutoffs, high probability patients are directly selected for CTPA and the others perform CTPA if Ddimer ≥500µg/L or age x10 µg/L within patients over 50 years, respectively. YEARS includes 3 items (signs of deep vein thrombosis, haemoptysis and whether PE is the most likely diagnosis): patients without any YEARS items and Ddimer ≥1000ng/mL or with ≥1 items and Ddimer 500ng/mL perform CTPA. In the PEGeD, patients with high clinical probability or with intermediate and Ddimers >500µg/L or low probability and Ddimer >1000 µg/L are selected for CTPA.
Results
We enrolled 409 patients and PE was confirmed by CTPA in 125 patients. Compared with a fixed Ddimer cutoff, age-adjusted was associated with a significant increased of specificity (p < 0.001), correctly avoiding 29 CTPAs, without losing sensitivity. YEARS resulted in a marked increase in specificity, compared to the fixed cutoff, but with an impairment of sensitivity(p = 0.002). PEGeD had the worst sensitivity, associated with 11 more false negatives (FN) than the fixed cutoff. Despite the lack of difference between PEGed and YEARS strategies regarding sensitivity, YEARS had a significantly higher specificity (p < 0.001) and allowed to correctly avoid a higher number of CTPA(55 vs 63), compared to the fixed cutoff. Results are summarized in table 1.
Conclusion
Compared to fixed d-dimer cutoff, all algorithms were associated with an increased specificity. Age-adjusted cutoff was the only that is not associated with a significant decrease in sensitivity when compared to fixed cutoff, allowing to safely reduce the need to perform CTPA.
Sens(%) Spec(%) Correctly avoid CTPAs(n) FN(n) Fixed cutoff 95 29 85 6 Age-adjusted 93 40 114 9 YEARS 87 52 148 16 PEGeD 86 49 140 17
Background and aims
COVID-19 is a multi-system disease, with coagulation abnormalities. D-dimer levels are increased in this disease. We aimed to determine the association of D-dimer levels and mortality and to establish its optimal cut off values in predicting mortality. Association of D-dimer levels with diabetes mellitus has also been established.
Methods
Information on 483 patients with confirmed COVID-19 was retrospectively collected and analyzed. The optimal D-dimer cutoff point and C-statistic of routine tests both on admission and during hospital stay were evaluated by receiver operator characteristic (ROC) curve.
Results
D-dimer elevation (≥0.50 μg/mL) was seen in 80.1% of the hospitalized patients. D-dimer level ≥2.01 μg/mL was a significant predictor of subsequent deaths (P < 0.01; HR, 3.165; 95% CI, 2.013–4.977). High D-dimer values (≥0.50 μg/mL) were observed in 72 of the 75 (96%) cases with a fatal outcome. Median D-dimer value among non-survivors was 6.34 μg/mL and among survivors it was 0.94 μg/mL. A higher proportion of fatal outcomes occurred in patients with underlying disease (89.0%), most prominent of which was diabetes mellitus (66%). The median D-dimer value was found to be significantly high in diabetic patients (1.68 μg/mL).
Conclusions
Among the measured coagulation parameters, D-dimer during hospital stay had the highest C-index to predict in-hospital mortality in COVID-19 patients. D-dimer value ≥ 2.01 μg/mL can effectively predict in-hospital mortality in patients with COVID-19. A significant association of increased D-dimer level has been found with diabetes mellitus and elderly age.
Introduction
COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available.
Methods
We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.
Results
We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.
Conclusion
The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
Background
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.
Methods
In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.
Findings
191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days.
Interpretation
The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Funding
Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
Cirrhotic patients with decompensated state and high serum levels of fibrin(ogen) degradation products are at high risk of bleeding. The aim of this study was to further analyse the relationship between hyperfibrinolysis and bleeding in cirrhosis by measuring plasma values of D-dimer and tissue plasminogen activator (t-PA) activity. One-hundred-twelve cirrhotic patients with oesophageal varices and without previous upper-gastrointestinal bleeding entered the study and were followed-up for 3 years. Patients were considered to have hyperfibrinolysis if they concomitantly had high values of D-dimer and t-PA activity. During the follow-up 34 (30%) patients bled. They had more severe liver failure (p = 0.0001) and variceal size (p = 0.0031) and higher prevalence of ascites (p = 0.0003), varices with red signs and hyperfibrinolysis (p = 0.0001) than patients who did not bleed. Multivariate analysis disclosed hyperfibrinolysis as the only marker predictive of bleeding (Hazard Ratio = 42.5, p <0.001). Our findings suggest that screening for hyperfibrinolysis may be useful to identify cirrhotic patients at risk of bleeding.
D-dimer is a soluble fibrin degradation product that results from ordered breakdown of thrombi by the fibrinolytic system. Numerous studies have shown that D-dimer serves as a valuable marker of activation of coagulation and fibrinolysis. Consequently, D-dimer has been extensively investigated for the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and as an aid in the identification of medical patients at high risk for VTE. Thus, quantification of D-dimer levels serves an important role in guiding therapy. This review: 1) describes how D-dimer is generated; 2) reviews the assays used for its detection; and 3) discusses the role of D-dimer determination in these various conditions.
Background
An elevated level of von Willebrand factor (VWF) is associated with an increased risk for coronary heart disease and ischemic stroke. The objective of the study was to determine whether the level of VWF is associated with the cardioembolic subtype of ischemic stroke, stroke severity, and clinical outcome. Patients and methodsIn this study 108 patients suffering from acute ischemic stroke (AIS) were included. According to the etiology of the stroke, patients were classified into the subtype of cardioembolic (CE) stroke and the group with non-CE stroke. Patients with non-CE stroke were further classified into subtype of large vessel disease, subtype of small vessel disease and subtype of cryptogenic stroke. Laboratory tests were performed in the acute phase and VWF was determined for all patients. The National Institutes of Health Stroke Scale (NIHSS) was applied on admission and the modified Rankin scale (MRS) at discharge. ResultsThe only significant factor which predicted CE stroke was age (B = 0.077; standard error, SE = 0.026; P = 0.003). The level of VWF was not significantly higher in the group with the cardioembolic stroke compared to the group with non-CE stroke. Patients assessed by NIHSS on admission as the most disabled had significantly higher levels of VWF (B = 0.006; SE = 0.003; P = 0.045). Those with higher scores of MRS at discharge also had significantly increased levels of VWF (B = 0.006; SE = 0.003; P = 0.028). Conclusion
Among the patients with ischemic stroke, levels of VWF were not increased in those with CE stroke. High levels of VWF were associated with greater severity of stroke as well as with poor clinical outcome.
direct link: http://www.njmonline.nl/getpdf.php?id=1790
Background: D-dimer is routinely measured as part of the clinical diagnosis algorithms for venous thromboembolism (VTE). In these algorithms, low D-dimer cut-off values are used to generate a dichotomous test result that is sensitive, but very non-specific for VTE. A consequence of any test dichotomisation is loss of information that is hidden in the continuous spectrum of results. For D-dimer, the information conveyed by extremely elevated results may be particularly relevant. Our aim was to assess the differential diagnosis of
extremely elevated D-dimer levels in a hospital setting.
Methods: Retrospective cohort study of patients > 18 years with an extremely elevated (> 5000 µg/l; > 10x cut-off to exclude VTE) D-dimer test result. Electronic medical records were reviewed for diagnoses.
Results: A total of 759 extremely elevated D-dimer results were identified. After exclusion of 120 duplicate cases, 53 patients undergoing cardiopulmonary resuscitation, and 5 cases without diagnostic information, 581 cases were analysed. Their D-dimer ranged between 5030 and 239,000 µg/l, with a mean of 17,598 µg/l (SD 22,972 µg/l). Altogether, 89% of these patients had a diagnosis of VTE, sepsis and/or cancer. The prevalence was highest for pulmonary embolism (183 patients; 32%), followed by cancer (168 patients; 29%), sepsis (142 patients; 24%), trauma/surgery (142 patients; 24%), and deep vein thrombosis (73 patients; 13%).
Conclusion: Although D-dimer testing has a reputation for being very non-specific, an extremely elevated D-dimer is uniquely associated with severe disease, mainly including VTE, sepsis and/or cancer. These results suggest that, even if sharply elevated D-dimers are a seemingly solitary finding, clinical suspicion of severe underlying disease should be maintained.
Background:
D-dimer is a fibrin degradation product and a possible marker of thromboembolic events. The aim of this study was to investigate the relationship between D-dimer levels and outcome in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis.
Methods:
This retrospective study included AIS patients who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and provided plasma D-dimer level within 24 h after stroke onset during 2009 and 2014 at a single medical center. Unfavorable outcome was defined as modified Rankin scale ≥3 at 3 months after stroke. Symptomatic intracerebral hemorrhage (ICH) was defined as a deterioration of at least 4 points on the National Institutes of Health Stroke Scale within 36 h post thrombolysis.
Results:
Of 347 patients receiving intravenous rt-PA, 159 (mean age 67.6 ± 13.1 year, 59.7% male) fulfilled the inclusion criteria. In univariate analysis, patients with unfavorable outcome (n = 79) had significantly higher levels of D-dimer than those with favorable outcome (median ln D-dimer = 1.4 vs. 0.7 μg/ml, p < 0.001). After adjustment for clinical variables, a higher level of D-dimer remained significantly associated with an unfavorable outcome (OR 1.90, 95% CI 1.27-2.86, p = 0.002) and the occurrence of symptomatic ICH (OR 2.97, 95% CI 1.15-7.70, p = 0.025).
Conclusion:
The D-dimer level within 24 h after stroke onset can be an early outcome indicator in AIS patients receiving rt-PA therapy.
Background: The diagnosis and management of acute ischemic stroke are limited by the lack of rapid diagnostic assays for use in an emergency setting. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective (<33% sensitive) in detecting ischemic stroke. The ability to correlate blood-borne protein biomarkers with stroke phenotypes would aid in the development of such rapid tests.
Methods: ELISAs for >50 protein biomarkers were developed for use on a high-throughput robotic workstation. These assays were used to screen plasma samples from 214 healthy donors and 223 patients diagnosed with stroke, including 82 patients diagnosed with acute ischemic stroke. Marker assay values were first compared by univariate analysis, and then the top markers were subjected to multivariate analysis to derive a marker panel algorithm for the prediction of stroke.
Results: The top markers from this analysis were S-100b (a marker of astrocytic activation), B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. In a panel algorithm in which three or more marker values above their respective cutoffs were scored as positive, these five markers provided a sensitivity of 92% at 93% specificity for ischemic stroke samples taken within 6 h from symptom onset.
Conclusion: A marker panel approach to the diagnosis of stroke may provide a useful adjunct to CT scanning in the emergency setting.
D-dimer tests are an essential element in the diagnostic work-up of deep venous thrombosis (DVT). However, the poor standardization amongst assays necessitates clinical validation before implementation in daily practice. We therefore evaluated the analytical and diagnostic performance of eight D-dimer tests in a representative group of 290 prospectively identified consecutive primary care patients with suspected DVT. Seven quantitative D-dimer assays, and a qualitative test, Simplify, were evaluated. Correlation between assays was generally poor and several assays showed a significant bias in the method comparison. Nevertheless, the Vidas D-dimer, Innovance D-dimer (CA1500 and BCS), Pathfast D-dimer, and HemosIL HS500 (ACL TOP), all displayed 100% (95% CI: 85-100%) sensitivity. Tina-quant (Modular), AQT90 D-dimer, and Liatest (STA(®)) D-dimer tests showed a slightly lower sensitivity of 95% (78-100%). and the Simplify test reached a sensitivity of 91% (72-99%) that was further improved in combination with a clinical decision rule to 95% (76-100%). In concert with the low (8.2%) prevalence of proximal DVT, diagnosed by compression ultrasonography, in our study, all test reached a negative predictive value (NPV) of at least 99%. The user friendliness of the assays differed mainly by stability of reagents, calibration frequency, time required to obtain a test result and costs of a test. In conclusion, despite considerable analytical differences, in our low-risk population all tests evaluated displayed an excellent NPV. In combination with a validated clinical decision rule to identify low-risk patients, even a straightforward POC solution could safely and cost-efficiently rule out DVT.
Background: Despite extensive literature, the diagnostic role of D-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple D-dimer assays and concerns about differing sensitivities and variability. Purpose: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among D-dimer assays. Data Sources: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003. Study Selection: The researchers selected prospective studies that compared o-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies. Data Extraction: Two authors collected data on study-level factors: D-dimer assay used, cutoff value, and whether patients had suspected DVT or PE. Data Synthesis: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings. Limitations: Although many studies evaluated multiple D-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies. Conclusion: The ELISAs in general dominate the comparative ranking among the D-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.
Little is known, in man, in the post-thrombolytic molecular dynamics of haemostasis, particularly the effect of rt-PA on antifibrinolytic components such as alpha2 anti-plasmin and Factor XIII.
The purpose of this study was to systematically determine changes in coagulation and fibrinolytic parameters after thrombolysis with rt-PA during 24h. We also aimed to correlate these parameters with different acute ischemic stroke subtypes and global outcome.
Eighty consecutive patients with cerebral infarcts treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers measured at baseline (h0), 2 (h2) and 24h (h24) after initiation of thrombolysis. Correlations between the variations of these components were statistically studied, using the Spearman rank test or the Pearson test. These haemostatic parameters were also compared with cardioembolic and non cardioembolic patients, as well as between poor and favourable outcome patients.
Between h0 and h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII was observed, while an increase in FDP and D-Dimers took place. These values returned to the initial levels at h24. At 2h, the decrease in fibrinogen was significantly correlated with that of plasminogen (0.48, p=0.01), alpha2-antiplasmin (0.48, p=0.004), and factor XIII (0.44, p=0.01); the decrease in plasminogen was significantly correlated with those of antifibrinolytic components, factor XIII (0.47, p=0.02) and alpha2-antiplasmin (r=0.77, p<0.001). These variations were independent of NIHSS. Cardioembolic infarcts showed a statistically significant greater h0-h2 decrease in plasminogen (p=0.04) and an h0-h2 increase in FDP (p=0.02). Poor outcome was linked to low plasminogen values at 2 and 24h.
Supposed to be fibrin-specific, rt-PA induces a decrease in circulating fibrinogen, significantly linked to a decrease in plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII and alpha2-antiplasmin is also observed. At 2h, a significant decrease in plasminogen and a significant increase in fibrin(ogen) degradation products (FDP) are observed in cardioembolic infarcts, and appear as early independent predictors of this aetiology. A low plasminogen value at 2h is potentially predictive of poor prognosis at 3months.
Copyright © 2015 Elsevier B.V. All rights reserved.
Major stroke clinical trials have failed during the past decades. The failures suggest the presence of heterogeneity among stroke patients. Biomarkers refer to indicators found in the blood, other body fluids or tissues that predicts physiologic or disease states, increased disease risk, or pharmacologic responses to a therapeutic intervention. Stroke biomarkers could be used as a guiding tool for more effective personalized therapy.
Three aspects of stroke biomarkers are explored in detail. First, the possible role of biomarkers in patients with stroke is discussed. Second, the limitations of conventional biomarkers (especially protein biomarkers) in the area of stroke research are presented with the reasons. Lastly, various types of biomarkers including traditional and novel genetic, microvesicle, and metabolomics-associated biomarkers are introduced with their advantages and disadvantages. We especially focus on the importance of comprehensive approaches using a variety of stroke biomarkers.
Although biomarkers are not recommended in practice guidelines for use in the diagnosis or treatment of stroke, many efforts have been made to overcome the limitations of biomarkers. The studies reviewed herein suggest that comprehensive analysis of different types of stroke biomarkers will improve the understanding of individual pathophysiologies and further promote the development of screening tools for of high-risk patients, and predicting models of stroke outcome and rational stroke therapy tailored to the characteristics of each case.
Context:
D-dimer is widely used for exclusion, or as an aid in diagnosis, of venous thromboembolism (VTE); however, the D-dimer assay methods available from manufacturers and the laboratory application of those methods vary widely.
Objectives:
To describe the current laboratory practice regarding the assay and reporting of D-dimer.
Design:
Laboratories' D-dimer proficiency testing data were analyzed and laboratory practices regarding the performance and reporting of D-dimer were surveyed.
Results:
Initial grading of D-dimer proficiency testing demonstrated high variability within and among methods. This variability continued to be present for several years after attempts to intervene. The number of laboratories using D-dimer to exclude VTE grew from 1500 in 2004 to more than 3500 in 2012. Survey and proficiency testing data demonstrated that 33% of laboratories changed the type or magnitude of units from that recommended by the manufacturer, a practice associated with as much as a 20-fold increase in the failure of proficiency testing. Many laboratories used a threshold for the exclusion of VTE that is higher than that recommended by the manufacturer. Many laboratories continue to use qualitative assays with insufficient sensitivity for exclusion of VTE.
Conclusions:
There is considerable variability both within and among quantitative methods used to assay D-dimer by laboratories. Laboratory practice continues to vary widely regarding the type and magnitude of units reported and the setting of the threshold for the exclusion of VTE. Although improved, the variability continues despite initial efforts to intervene.
Outcomes in acute pulmonary embolism (PE) are dictated by both patient factors and the hemodynamic consequences of pulmonary thromboembolism. Risk stratification in acute PE can be performed via clinical scoring systems, biomarkers, and imaging studies, including transthoracic echocardiography and CT angiography. Furthermore, there is a growing literature on the combination of risk stratification methods to better estimate outcomes. Whereas the negative predictive value for adverse events is high for many risk prediction tools, positive predictive value for all of these techniques, except in those patients who present in cardiogenic shock, remains low.
The significance of asymptomatic coronary artery atherosclerosis burden (CAB) in the interpretation of stroke biomarker results is unknown. We investigated biomarker values to determine if they are related to cerebral atherosclerosis with consideration of CAB.
We prospectively recruited patients with noncardioembolic ischemic cerebrovascular disease who had no history of coronary artery disease. Patient-based vascular assessment was conducted using MRA for the cerebral arteries and cardiac CT angiography for the coronary arteries. Biomarkers including the C-reactive protein and homocysteine were measured.
A total of 178 patients were included in the study. The extracranial carotid stenosis was associated with the highest quartile of C-reactive protein (OR, 2.24; 95% CI, 1.04-4.55), whereas age was the only predictor of the highest quartile of homocysteine (OR, 1.06; 95% CI, 1.02-1.11). However, with consideration of CAB, CAB (≥2 segments with ≥50% stenosis) remained the only independent predictor for the highest quartile of C-reactive protein (OR, 8.69; 95% CI, 2.41-31.30) and homocysteine (OR, 11.44; 95% CI, 2.61-50.11).
Our data emphasize the importance of CAB in biomarker studies of patients with ischemic stroke.
Changes in coagulation may have a profound impact on outcomes following severe burns and the coagulation abnormalities after thermal injury are incompletely described. We postulated that thermal injury induces a systemic hypercoagulable state. With Institutional Review Board approval, five patients were consented for enrollment in this case series. After obtaining informed consent, blood was drawn on hospital days 1, 2, 3, 5, and 7 or until discharge if discharge was in less than 7 days. Standard coagulation testing was performed, as well as a battery of sophisticated specialized coagulation assays. Other data collected includes fluid resuscitation volumes, pharmacologic interventions, and general physiologic information. Results (n = 5) demonstrate that burns less than 6% total body surface area appear to have little effect on coagulation. Burns greater than 6% appear to induce a systemic hypercoagulable state with a phase and magnitude relationship proportional to total body surface area burned. Severe burns greater than 40% appear to induce a consumptive coagulopathy. Prothrombin fragment 1.2 may represent a useful screening test for a burn-induced hypercoagulable state.
Coronary artery disease (CAD) is a significant cause of morbidity and mortality in stroke patients. Some patients with asymptomatic CAD might benefit from specific prevention, but the prevalence of asymptomatic CAD is not well known. We assessed the prevalence of >or=50% asymptomatic CAD in patients with ischemic stroke or transient ischemic attack and whether the prevalence is related to traditional vascular risk factors and cervicocephalic atherosclerosis.
From January 2006 to February 2009, consecutive patients between 45 and 75 years of age with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack and no prior history of CAD were enrolled in the study. All patients had a 64-section computed tomography coronary angiography and a detailed cervicocephalic arterial workup. Risk factors were assessed individually and through the Framingham Risk Score. Among 300 patients included in the study, 274 had computed tomography coronary angiography. The prevalence of >or=50% asymptomatic CAD was 18% (95% confidence interval [CI], 14 to 23; n=50). Asymptomatic CAD was independently associated with traditional risk factors assessed individually and through the Framingham Risk Score (odds ratio [OR], 2.6; 95% CI, 1.0 to 7.6 for a 10-year risk of coronary heart disease of 10% to 19%; and OR, 7.3; 95% CI, 2.8 to 19.1 for a 10 year-risk of coronary heart disease >or=20%), the presence of at least 1 >or=50% cervicocephalic artery stenosis (OR, 4.0; 95% CI, 1.4 to 11.2), excessive alcohol consumption (OR, 3.1; 95% CI 1.3 to 7.3), and ankle brachial index <0.9 (OR, 2.2; 95% CI, 0.9 to 5.2). The prevalence of >or=50% asymptomatic CAD was also related to the extent of cervicocephalic atherosclerosis.
About one fifth of patients with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack have >or=50% asymptomatic CAD. In addition to vascular risk factors, the presence of >or=50% cervicocephalic artery stenosis is strongly related to >or=50% asymptomatic CAD.
Background:
Stroke is a devastating condition encompassing a wide range of pathophysiological entities that include thrombosis, hemorrhage, and embolism. Current diagnosis of stroke relies on physician clinical examination and is further supplemented with various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in an acute setting to diagnosis stroke, differentiate between stroke types, or even predict an initial/reoccurring stroke would be extremely valuable.
Content:
We discuss the current classification, diagnosis, and treatment of stroke, focusing on use of novel biomarkers (either solitary markers or multiple markers within a panel) that have been studied in a variety of clinical settings.
Summary:
The current diagnosis of stroke remains hampered and delayed due to lack of a suitable mechanism for rapid (ideally point-of-care), accurate, and analytically sensitive biomarker-based testing. There is a clear need for further development and translational research in this area. Potential biomarkers identified need to be transitioned quickly into clinical validation testing for further evaluation in an acute stroke setting; to do so would impact and improve patient outcomes and quality of life.