Prediction of cerebral venous thrombosis with a new clinical score and D-dimer levels

ObjectiveTo investigate prediction of cerebral venous thrombosis (CVT) by clinical variables and D-dimer levels.MethodsThis prospective multicenter study included consecutive patients with clinically possible CVT. On admission, patients underwent clinical examination, blood sampling for D-dimers measuring (ELISA test), and magnetic resonance/CT venography. Predictive value of clinical variables and D-dimers for CVT was calculated. A clinical score to stratify patients into groups with low, moderate, or high CVT risk was established with multivariate logistic regression.ResultsCVT was confirmed in 26.2% (94 of 359) of patients by neuroimaging. The optimal estimate of clinical probability was based on 6 variables: seizure(s) at presentation (4 points), known thrombophilia (4 points), oral contraception (2 points), duration of symptoms >6 days (2 points), worst headache ever (1 point), and focal neurologic deficit at presentation (1 point) (area under the curve [AUC] 0.889). We defined 0 to 2 points as low CVT probability (negative predictive value [NPV] 94.1%). Of the 186 (51.8%) patients who had a low probability score, 11 (5.9%) had CVT. The frequency of CVT was 28.3% (34 of 120) in patients with a moderate (3–5 points) and 92.5% (49 of 53) in patients with a high (6–12 points) probability score. All low CVT probability patients with CVT had D-dimers >500 μg/L. Predictive value of D-dimers for CVT for >675 μg/L (best cutoff) vs >500 μg/L was as follows: sensitivity 77.7%, specificity, 77%, NPV 90.7%, and accuracy 77.2% vs sensitivity 89.4%, specificity 66.4%, NPV 94.6%, and accuracy 72.4%, respectively. Adding the clinical score to D-dimers >500 μg/L resulted in the best CVT prediction score explored (at the cutoff ≥6 points: sensitivity 83%/specificity 86.8%/NPV 93.5%/accuracy 84.4%/AUC 0.937).ConclusionThe proposed new clinical score in combination with D-dimers may be helpful for predicting CVT as a pretest score; none of the patients with CVT showed low clinical probability for CVT and D-dimers <500 μg/L.ClinicalTrials.gov identifierNCT00924859.

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Combination of a Normal D-Dimer Concentration and a Non-High Pretest Clinical Probability Score Is a Safe Strategy to Exclude Deep Venous Thrombosis

Circulation ◽

10.1161/01.cir.0000045670.12988.1e ◽

2003 ◽

Vol 107 (4) ◽

pp. 593-597 ◽

Cited By ~ 107

Author(s):

R.E.G. Schutgens ◽

P. Ackermark ◽

F.J.L.M. Haas ◽

H.K. Nieuwenhuis ◽

H.G. Peltenburg ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Probability Score ◽

Clinical Probability ◽

Safe Strategy ◽

D Dimer

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Soluble P-Selectin and Age Adjusted D-Dimer As Predictive Biomarkers of Venous Thrombosis

Blood ◽

10.1182/blood.v124.21.2863.2863 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2863-2863

Author(s):

Dana E Angelini ◽

Cathy Stabler ◽

Angela E. Hawley ◽

Kenneth E. Guire ◽

Daniel Durant Myers ◽

...

Keyword(s):

Lower Extremity ◽

Predictive Value ◽

Duplex Ultrasound ◽

The Elderly ◽

Probability Score ◽

Clinical Probability ◽

Wells Score ◽

History Of ◽

D Dimer ◽

Rule Out

Abstract Introduction: Accurate and rapid diagnosis is essential in acute venous thromboembolism (VTE) to help prevent significant morbidity and mortality. Soluble P-selectin (sP-sel) is a cell surface ligand that aids in cell adhesion. It is released from activated platelets and damaged endothelial cells resulting in release of procoagulant molecules from leukocytes and aiding in thrombus generation. Our lab has previously shown elevated sP-sel is highly predictive of VTE in combination with clinical probability (Wells score). Current standards for ruling out VTE include combining Wells Score and plasma D-dimer; however, D-dimer increases with age and is less useful in the elderly. Age adjusted D-dimer, defined as 10*age in patients ≥50 years old, has been described as being more sensitive, which could rule out more clots in the elderly, sparing them from other diagnostic tests. Methods: We performed a prospective cohort study of patients ≥18 years old who presented with symptoms of deep venous thrombosis (DVT) in upper or lower extremities from December 2008 to July 2013. Exclusion criteria included isolated calf DVT, superficial thrombosis, indeterminate duplex scans, pregnancy or nursing mothers, therapeutic anticoagulation, and symptoms of simultaneous upper and lower extremity (LE) clot. After informed consent was obtained, biomarkers were drawn and duplex ultrasound was used to confirm or deny presence of acute clot. Our objective was to examine the accuracy of biomarker combinations and clinical probability score to rule in or rule out acute venous thrombus. Results: We recruited 461 patients to the study. Patients with positive lower extremity DVT were significantly more likely to be male, have a prior history of DVT, have active cancer or history of cancer, and be inpatient. Table 1: Biomarkers and Clinical Probability Score of Patients Presenting with Symptoms of LE DVT Table 1:. Biomarkers and Clinical Probability Score of Patients Presenting with Symptoms of LE DVT There were no significant differences in biomarkers between upper and lower extremity VTE aside from non-significance of sP-sel in upper extremity clots. We calculated the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of several combinations of biomarkers and clinical probability assessment. Table 2: Specificity and PPV Table 2:. Specificity and PPV Table 3: Sensitivity and NPV Table 3:. Sensitivity and NPV Using the age adjusted D-dimer did not improve the overall sensitivity when compared to the traditional cut off. However, sub-analysis demonstrated using D-dimer <500 ng/mL in those ≥ 50 ruled out 35 patients while the age adjusted D-dimer ruled out an additional 17 patients (12% increase). An additional 10% of patients ≥60 years were ruled out using the age adjusted D-dimer alone; this benefit rose to 15% in patients ≥70 years old. Use of the age adjusted D-dimer did not increase false negative results. Conclusions: We found Wells ≥ 2 and sP-sel ≥ 90 ng/mL had the highest specificity of any combination of biomarkers, highlighting its clinical utility as a predictive biomarker of thrombosis. Using this combination would allow clinicians to accurately rule in venous thrombus without need for further imaging. In this study, we would have successfully identified 48 (25%) patients with acute thrombus without duplex ultrasound. Compared to the traditional cut off value, age adjusted D-dimer did not increase sensitivity in those >age 50, but its utility increased with age, making it a promising biomarker to safely rule out thrombosis in the elderly. Disclosures No relevant conflicts of interest to declare.

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Abstract W P266: A Simple Score for Prediction of Outcome after Cerebral Venous Thrombosis

Stroke ◽

10.1161/str.46.suppl_1.wp266 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Miguel A Barboza ◽

Erwin Chiquete ◽

Antonio Arauz ◽

Jonathan Colín ◽

Alejandro Quiroz-Compean ◽

...

Keyword(s):

Decision Making ◽

Venous Thrombosis ◽

Predictive Value ◽

Cerebral Venous Thrombosis ◽

Goodness Of Fit ◽

Clinical Decision Making ◽

Case Fatality ◽

Clinical Decision ◽

Classification Systems ◽

Cox Proportional Hazards Model

Background and purpose: Cerebral venous thrombosis (CVT) not always implies a good prognosis. There is a need for robust and simple classification systems of severity after CVT that help in clinical decision-making. Methods: We studied 467 patients (81.6% women, median age: 29 years, interquartile range: 22-38 years) with CVT who were hospitalized from 1980 to 2014 in two third-level referral hospitals. Bivariate analyses were performed to select variables associated with 30-day mortality to integrate a further multivariate analysis. The resultant model was evaluated with the Hosmer-Lemeshow test for goodness of fit, and on Cox proportional hazards model for reliability of the effect size. After the scale was configured, security and validity were tested for 30-day mortality and modified Rankin scale (mRS) >2. The prognostic performance was compared with that of the CVT risk score (CVT-RS, 0-6 points) as the reference system. Results: The 30-day case fatality rate was 8.7%. The CVT grading scale (CVT-GS, 0-9 points) was integrated by stupor/coma (4 points), parenchymal lesion >6 cm (2 points), mixed (superficial and deep systems) CVT (1 point), meningeal syndrome (1 point) and seizures (1 point). CVT-GS was categorized into mild (0-3 points, 1.1% mortality), moderate (4-6 points, 19.6% mortality) and severe (7-9 points, 61.4% mortality). For 30-day mortality prediction, as compared with CVT-RS (cut-off 4 points), CVT-GS (cut-off 5 points) was globally better in sensitivity (85% vs 37%), specificity (90% vs 95%), positive predictive value (44% vs 40%), negative predictive value (98% vs 94%), and accuracy (94% vs 80%). For 30-day mRS >2 the performance of CVT-GS over CVT-RS was comparably improved. Conclusion: The CVT-GS is a simple and reliable score for predicting outcome that may help in clinical decision-making and that could be used to stratify patients recruited into clinical trials.

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Can a negative D-Dimer Test help in ruling out the diagnosis of Cerebral Venous Thrombosis?

Journal of Emergency Medicine Trauma and Acute Care ◽

10.5339/jemtac.2022.qhc.44 ◽

2021 ◽

Vol 2022 (1) ◽

Author(s):

Ahmed Abdu Obeid Kassem ◽

Mohammed Ahmed Seif Mohamed ◽

Thirumoorthy Suresh Kumar

Keyword(s):

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

D Dimer

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D-dimer combined with clinical probability assessment for exclusion of acute deep venous thrombosis

Pulmonary Embolism ◽

10.1002/9781119039112.ch46 ◽

2016 ◽

pp. 234-235

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Probability Assessment ◽

Clinical Probability ◽

D Dimer

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The Performance of CT versus MRI in the Differential Diagnosis of Cerebral Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642636 ◽

2018 ◽

Vol 118 (06) ◽

pp. 1067-1077 ◽

Cited By ~ 2

Author(s):

Weilin Xu ◽

Liansheng Gao ◽

Tao Li ◽

Neha Ramdoyal ◽

Jianmin Zhang ◽

...

Keyword(s):

Differential Diagnosis ◽

Diagnostic Accuracy ◽

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

Sinus Thrombosis ◽

Meta Analysis ◽

Area Under The Curve ◽

Significant Heterogeneity ◽

Summary Receiver Operating Characteristic ◽

Ct And Mri

Background Cerebral venous thrombosis (CVT) is a rare disease, and with poor prognosis. Computed tomography (CT) and magnetic resonance imaging (MRI) are the most commonly used image modalities for patients with non-specific neurologic symptoms. We present here a meta-analysis to assess the accuracy of CT and MRI in the differential diagnosis of CVT and cerebral venous sinus thrombosis (CVST). Materials and Methods A comprehensive search of the PubMed, EMBASE, Web of Science, Cochrane Database and Chinese Biomedical (CBM) databases was conducted prior to March 20, 2017. In this report, we assess the methodological quality of each article individually and perform a meta-analysis to obtain the summary of the diagnostic accuracy of CT and MRI in correctly identifying CVT and CVST. Results Twenty-four eligible articles comprising 48 studies (4,595 cases) were included. The pooled sensitivity for CT–CVT/CT–CVST groups is 0.79 (95% confidence interval [CI]: 0.76, 0.82)/0.81(95% CI: 0.78, 0.84), and pooled specificity is 0.90 (95% CI: 0.89, 0.91)/0.89 (0.88, 0.91), with an area under the curve (AUC) for the summary receiver operating characteristic (SROC) of 0.9314/0.9161, respectively. No significant heterogeneity and publication bias was observed across each study. For MRI–CVT/MRI–CVST, the pooled sensitivity is 0.82 (95% CI: 0.78, 0.85)/0.80 (95% CI: 0.76, 0.83), and pooled specificity is 0.92 (95% CI: 0.91, 0.94)/0.91(0.89, 0.92), with an AUC for the SROC of 0.9221/0.9273, respectively. Conclusion This meta-analysis indicates that both CT and MRI have a high level of diagnostic accuracy in the differential diagnosis of CVT and CVST, independent of stage, target for analysis or analysis methods. They could be chosen as alternative sub-optimal gold standards for diagnosing CVT and CVST, especially in emergency.

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LO06: Role of the age adjusted D-dimer in suspected deep venous thrombosis

CJEM ◽

10.1017/cem.2017.68 ◽

2017 ◽

Vol 19 (S1) ◽

pp. S29

Author(s):

P. Reardon ◽

S. Patrick ◽

M. Taljaard ◽

K. Thavorn ◽

M.A. Mukarram ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Older Patients ◽

Large Scale ◽

False Negative ◽

Cost Savings ◽

Low Risk ◽

Clinical Probability ◽

D Dimer

Introduction: It is well established that a negative D-dimer will reliably rule out thromboembolism in selected low risk patients. Multiple modified D-dimer cutoffs have been suggested for older patients to improve diagnostic specificity. However, these approaches are better established for pulmonary embolism than for deep venous thrombosis (DVT). This study will evaluate the diagnostic performance of previously suggested D-dimer cutoffs for low risk DVT patients in the ED, and assess for a novel cutoff with improved performance. Methods: This health records review included patients >50 years with suspected DVT who were low-risk and had a D-dimer performed. Our analysis evaluated the diagnostic accuracy of D-dimer cutoffs of 500 and the age adjusted (age x 10) rule for patients >50 years; and 750, and 1,000 cutoffs for patients >60 years. 30-day outcome was a diagnosis of DVT. We also assessed the diagnostic accuracy for a novel cutoff (age x 12.5). Results: 1,000 patients (mean age 68 years; 59% female) were included. Of these, 110 patients (11%) were diagnosed with DVT. The conventional cutoff of <500 µg/L demonstrated a sensitivity of 99.1% (95% CI 95.0-99.9) and a specificity of 36.4% (95% CI 33.2-39.7). For patients >60 years, the absolute cutoffs of 750 and 1,000 showed sensitivity of 98.7% (95% CI, 92.9, 99.9), and the specificity increased to 48.6% (95% CI, 44.5-52.8%) and 62.1% (95% CI, 58.1-66.1%) respectively. For all study patients, age adjusted D-dimer demonstrated a sensitivity of 99.1% (95% CI 95.0-99.9) and a specificity of 51.2% (95% CI, 47.9-54.6). A novel age adjusted cutoff (age x 12.5) for patients >50, demonstrated a sensitivity of 97.3% (95% CI 92.2-99.4) and a specificity of 61.2% (95% CI 58.0-64.5). When compared to conventional cutoff, the age adjusted cutoffs (age x 10 and age x 12.5) would have resulted in an absolute decrease in further investigations of 13.1% and 22.2%, respectively, with false negative rates of 0.1% and 0.3%. Conclusion: Among older patients with suspected DVT and low clinical probability, the age adjusted D-dimer increases the proportion of patients among whom DVT can be ruled out. A novel cutoff (age x 12.5) demonstrated improved specificity. Future large scale prospective studies are needed to confirm this finding and to explore the cost savings of these approaches.

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Evidence for Safe Exclusion of Deep Vein Thrombosis (DVT) by a Rapid ELISA D-Dimeer Test at Cut-Off Levels of 500 and 1000 Ng/Ml in 1046 Consecutive Outpatients with Suspected DVT.

Blood ◽

10.1182/blood.v104.11.1059.1059 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1059-1059

Author(s):

Jan Jacques Michels ◽

Jan Hermssen ◽

Paul H. Trienekens

Keyword(s):

Deep Vein Thrombosis ◽

Negative Predictive Value ◽

Predictive Value ◽

Clinical Score ◽

Large Prospective Study ◽

Vein Thrombosis ◽

Persistent Symptoms ◽

Deep Vein ◽

D Dimer ◽

Compression Ultrasonography

Abstract Introduction.A normal compression ultrasonography (CUS) safely excludes proximal deep vein thrombosis (DVT) with a negative predictive value of 97% indicating the need to repeat CUS testing within one week. In 3 studies, the rapid ELISA D-dimer assay at a cut-off of 500 ng/ml did have a sensitivity of 100% for the exclusion of venographically documented distal and proximal DVT irrespective of clinical score. To test this hypothesis we performed a large prospective study in outpatients with suspected DVT. Methods. CUS and a rapid ELISA D-Dimer test (VIDAS, BioMérieux L’Etoile, France) were performed in patients with suspected DVT. A negative CUS with a D-Dimer result of <500 ng/ml exclude DVT, and with a D-Dimer result of >500 ng/ml was followed by a second CUS within one week. Results. The prevalence of DVT 1046 consecutive out patients with suspected DVT was 23,4%. The first CUS was positive in 228 with a rapid ELISA D-Dimer of >500 ng/ml in 227 and of <500 ng/ml in one case, indicating a sensitivity of 99,6% irrespective of clinical score. The first CUS was negative in 818. The rapid ELISA D-dimer test Was <500 ng/ml in 297 of which 296 had a negative first CUS indicating a negative predictive value of 99.7% at a specificity of 37% irrespective of the clinicl score. The negative predictive value of a negative CUS plus a rapid ELISA D-Dimer result of less than 1000 ng/ml is 99.5% at a specificity of 67,9% irrespective of clinical score. The prevalence of DVT in patients with negative first CUS and a ELISA D-Dimer of >1000 ng/ml was 5.6% as documented by CUS repeat within on week. Conclusion.A normal rapid ELISA D-dimer test, <500 ng/ml, in outpatients with suspected DVT safely excludes DVT irrespective of clinical score. After a negative rapid ELISA result (<500 ng/ml), CUS is still indicated for safety reasons in patients with suspected DVT and persistent symptoms in search for an alternative diagnosis, or for a rare case of DVT. A negative CUS plus and ELISA D-Dimer result of <1000 ng/ml safely exclude DVT without the need to repeat CUS in 2/3 of patients with a negative first CUS.

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