Exclusion Of Deep Vein Thrombosis Research Articles

Deep vein thrombosis and pulmonary embolism: a prospective, observational study to evaluate diagnostic performance of the Tina-quant D-Dimer Gen.2 assay.

D-Dimer testing is a diagnostic tool for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE). This study evaluated the diagnostic performance of the Tina-quant® D-Dimer Gen.2 assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in patients with low/intermediate pre-test probability of DVT/PE using standard, age-, and clinical probability-adjusted cut-offs. In this prospective, observational, multicenter study (July 2017-August 2019), plasma samples were collected from hospital emergency departments and specialist referral centers. DVT/PE was diagnosed under hospital standard procedures and imaging protocols. A standard D-dimer cut-off of 0.5 µg fibrinogen equivalent units (FEU)/ml was combined with the three-level Wells score; cut-offs adjusted for age (age × 0.01 µg FEU/ml for patients >50 years) and clinical probability (1 µg FEU/ml for low probability) were also evaluated. An assay comparison was conducted in a subset of samples using the Tina-quant D-Dimer Gen.2 assay and the previously established routine laboratory assay, STA-Liatest D-Di Plus assay (Stago Deutschland GmbH, Düsseldorf, Germany). 2,897 patients were enrolled; 2,516 completed the study (DVT cohort: 1,741 PE cohort: 775). Clinical assessment plus D-dimer testing using the standard cut-off resulted in 317 (DVT) and 230 (PE) false positives, and zero (DVT) and one (PE) false negatives. Negative predictive value (NPV) was 100.0% (95% confidence interval [CI]: 99.7%-100.0%) and 99.8% (95% CI: 98.8%-100.0%) for DVT and PE, respectively. After age-adjustment, NPV was 99.9% (95% CI: 99.6%-100.0%) and 99.1% (95% CI: 97.8-99.7) for DVT and PE, respectively. False positive rates decreased (>50%) in clinical probability-adjusted analyses vs. primary analysis. In the assay comparison, the performances of the two assays were comparable. The Tina-quant D-Dimer Gen.2 assay and standard D-dimer cut-off level combined with the three-level Wells score accurately identified patients with a very low probability of DVT/PE.

Evaluation of the diagnostic performance of three D-dimer assays in patients with suspected deep vein thrombosis: STA-Liatest D-Di plus, Tina-quant D-dimer Gen. 2, and INNOVANCE D-dimer

IntroductionD-dimer is a crucial test to exclude deep vein thrombosis (DVT). We aimed to evaluate the performance of three D-dimer assays: STA-Liatest D-Di Plus (Diagnostica Stago), Tina-quant D-Dimer Gen. 2 (Roche Diagnostics), and INNOVANCE D-Dimer (Siemens Healthineers Diagnostics) in the exclusion of DVT. MethodsSamples (n = 1032) and clinical data were acquired from a prospective outcome study (Rivaroxaban for Scheduled Work-up of Deep Vein Thrombosis – the Ri-Schedule study), which included patients referred to the emergency department with suspected lower-limb DVT. D-dimer was determined with STA-Liatest, and only patients with positive D-dimer values (≥0.5 μg/mL) as stand-alone, were referred for compression ultrasonography to confirm or exclude DVT. Patients were followed up 90 days after inclusion. Samples were also analyzed with Tina-quant Gen. 2, and INNOVANCE assays. The diagnostic performances of the three assays were investigated. ResultsPositive D-dimer (≥0.5 μg/mL) was found in 733 patients (71%) with STA-Liatest, 691 patients (67%) with Tina-quant Gen. 2, and 766 (74%) with INNOVANCE. DVT was confirmed by compression ultrasonography in 196 patients (27%) with positive D-dimer with STA-Liatest. Of those, six (3%) had negative D-dimer (<0.5 μg/mL) with at least one of the three assays yielding a failure rate of 0.7% with STA-Liatest, 2% with Tina-quant Gen. 2, and 2% with INNOVANCE. The sensitivity and negative predictive value (NPV) for STA-Liatest were 99.0% (95% CI 96.4–99.9) and 99.3% (95% CI 97.4–99.8), for Tina-quant Gen. 2 97.5% (95% CI 94.1–99.2) and 98.5% (95% CI 96.6–99.4), and for INNOVANCE 98.0% (95% CI 94.9–99.0) and 98.5% (95% CI 96.1–99.4) respectively. The efficiency to exclude DVT based on D-dimer as a stand-alone test was 29% (95% CI 26–33) for STA-Liatest, 33% (95% CI 30–37) for Tina-quant Gen. 2, and 26% (95% CI 23–29) for INNOVANCE. ConclusionSTA-Liatest, Tina-quant Gen. 2, and INNOVANCE showed good performances with sensitivity ≥97% and NPV ≥98%. The efficiency to exclude DVT varied and was highest for Tina-quant Gen. 2, whereas the failure rate was lowest for STA-Liatest.

Two point-of-care test-based approaches for the exclusion of deep vein thrombosis in general practice: a cost-effectiveness analysis

BackgroundIn the diagnostic work-up of deep vein thrombosis (DVT), the use of point-of-care-test (POCT) D-dimer assays is emerging as a promising patient-friendly alternative to regular D-dimer assays, but their cost-effectiveness is unknown. We compared the cost-effectiveness of two POCT-based approaches to the most common, laboratory-based, situation.MethodsA patient-level simulation model was developed to simulate the diagnostic trajectory of patients presenting with symptoms of DVT at the general practitioner (GP). Three strategies were defined for further diagnostic work-up: one based on current guidelines (‘regular strategy’) and two alternative approaches where a POCT for D-dimer is implemented at the 1) phlebotomy service (‘DVT care pathway’) and 2) GP practice (‘fast-POCT strategy’). Probabilities, costs and health outcomes were obtained from the literature. Costs and effects were determined from a societal perspective over a time horizon of 6 months. Uncertainty in model outcomes was assessed with a one-way sensitivity analysis.ResultsThe Quality-Adjusted Life Years (QALYs) scores for the three DVT diagnostic work-up strategies were all around 0.43 across a 6 month-time horizon. Cost-savings of the two POCT-based strategies compared to the regular strategy were €103/patient for the DVT care pathway (95% CI: -€117–89), and €87/patient for the fast-POCT strategy (95% CI: -€113–67).ConclusionsPoint-of-care-based approaches result in similar health outcomes compared with regular strategy. Given their expected cost-savings and patient-friendly nature, we recommend implementing a D-dimer POCT device in the diagnostic DVT work-up.

Clinical decision rules in primary care: necessary investments for sustainable healthcare.

Clinical judgement in primary care is more often decisive than in the hospital. Clinical decision rules (CDRs) can help general practitioners facilitating the work-through of differentials that follows an initial suspicion, resulting in a concrete 'course of action': a 'rule-out' without further testing, a need for further testing, or a specific treatment. However, in daily primary care, the use of CDRs is limited to only a few isolated rules. In this paper, we aimed to provide insight into the laborious path required to implement a viable CDR. At the same time, we noted that the limited use of CDRs in primary care cannot be explained by implementation barriers alone. Through the case study of the Oudega rule for the exclusion of deep vein thrombosis, we concluded that primary care CDRs come out best if they are tailor-made, taking into consideration the specific context of primary health care. Current CDRs should be evaluated frequently, and future decision rules should anticipate the latest developments such as the use of point-of-care (POC) tests. Hence, such new powerful diagnostic CDRs could improve and expand the possibilities for patient-oriented primary care.

P1697: EVALUATION OF THE DIAGNOSTIC PERFORMANCE OF THE TINA-QUANT D-DIMER GEN. 2 IN PATIENTS WITH SUSPECTED DEEP VEIN THROMBOSIS

Background: Combined with clinical pretest probability evaluation, D-dimer is a central element in the diagnostic work-up of suspected deep vein thrombosis (DVT). Different assays are available for the measurement of D-dimer. However, D-dimer assays are not standardized and the results are not comparable among the different assays. Therefore, the cut-off used to discriminate between positive and negative test results should be evaluated assay-wise in each institution. According to our best knowledge, only one study has evaluated the diagnostic performance of Tina-quant D-Dimer Gen. 2 assay in proximal DVT, and this study excluded patients with recurrent DVT. Aims: The aim of our study was to evaluate the diagnostic performance of the Tina-quant D-Dimer Gen. 2 assay (Roche Diagnostics) in the exclusion of all types of DVT, and to compare its performance with the STA-Liatest D-Di Plus (Stago). Methods: In the Ri-Schedule study (Rivaroxaban for Scheduled Work-up of Deep Vein Thrombosis; NCT 02486445), which was a prospective outcome study, D-dimer was measured with STA-Liatest D-Di Plus in 1653 adult patients referred to the Emergency Department at Østfold Hospital with suspected DVT. Exclusion criteria were failure to consent, and previous inclusion in the Ri-Schedule study within the past 3 months. Patients with D-dimer levels ≥ 0.5 µg/mL fibrinogen equivalent units (FEU) were referred to whole-leg compression ultrasonography (CUS) to confirm/exclude the DVT diagnosis. All patients were followed up after 90 days. To evaluate the diagnostic performance of the Tina-quant D-Dimer Gen. 2 assay, stored frozen plasma samples acquired from 1097 patient in the Ri-Schedule study were analyzed on Cobas t711. These samples were withdrawn simultaneously as the sample that were analyzed with the STA-Liatest D-Di Plus on STA-R. The diagnostic performance of the two assays were depicted and compared using test performance parameters and ROC curve. Results: Of the 1097 patients, 730 patients had a positive D-dimer with the Tina-quant D-Dimer Gen. 2, and 775 patients had a positive D-dimer with the STA-Liatest D-Di Plus; cut-off for both tests was ≥ 0.5 µg/mL FEU. DVT diagnosis was confirmed in 210 (19.2%) by CUS examination. The sensitivity and negative predictive value (NPV) for the Tina-quant D-Dimer Gen. 2 assay were 96.2% (95% CI 92.6–98.3) and 97.8% (95% CI 95.8–98.9) respectively; the specificity and positive predictive value (PPV) were 40.5% (95% 37.2–43.8) and 27.7% (95% CI 26.5–28.9) respectively (Table 1). The sensitivity and NPV for the STA-Liatest D-Di Plus assay were 98.1% (95% CI 95.2–99.5) and 98.8% (95% CI 96.8–99.5) respectively (Table 1). ROC curve analysis showed an AUC of 0.85 for both assays, with no significant differences between the assays. Of those with D-dimer value below the cut-off, 8 patients had DVT diagnosed by CUS at time of initial work up or during the subsequent 90 day with Tina-quant as compared with STA-D-Di Plus. Image:Summary/Conclusion: The Tina-quant D-Dimer Gen. 2 assay on Cobas t711 showed an overall good and comparable performance for the exclusion of DVT when compared with STA-Liatest D-Di Plus assay.

Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures

ObjectiveThis study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures.MethodsThis was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein.ResultsThere were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied.ConclusionsWe developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.

Evidence-Based Diagnosis of Venous Thromboembolism: A Systematic Review

Introduction: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, potentially lethal condition with acute morbidity. The purpose of this systematic review is to evaluate the literature for the evidence supporting the use of algorithms for the diagnosis of DVT and PE with a goal of a) ensuring the evidence is robust, b) determining if diagnostic approaches that don't use algorithms are acceptable, and c) identifying knowledge gaps that require further research.Methods: this systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of PubMed, EMBASE and MEDLINE (1990-May 2017) was conducted. The search was restricted to English-language only. The full text of all abstracts that met the basic eligibility criteria were assessed for inclusion or exclusion by two investigators independently. Disagreements were resolved by consensus.The key inclusion criteria were that the study was a high quality randomized clinical trial (RCT), meta-analysis, systematic review or prospective cohort study. The target outcomes of interest were the overall quality of development of the algorithms for the diagnosis of DVT and PE, the strength of evidence supporting their use, an assessment of the supporting evidence for diagnostic approaches that don't use algorithms, and the strengths and limitations of the body of evidence. The Scottish Intercollegiate Guidelines Network and the Consolidated Standards of Reporting Trials checklists were used to assess the quality of included RCTs and prospective studies. Assessing the Methodological Quality of Systematic Reviews tool was used to rate the quality of meta-analyses or systematic reviews. Low quality studies were excluded.Results: Twenty-six meta-analyses or systematic reviews, 8 RCTs and 24 well-performed prospective studies informed our review. The approach to the diagnosis of VTE has evolved over the years. There is considerable high quality evidence that an algorithmic approach, which uses a combination of pretest clinical probability and D-dimer testing followed by accurate imaging tests in selected patients, will enable the safest and most cost-effective diagnostic approach in outpatients with suspected VTE. However, these algorithms have not been extensively studied in hospitalized patients, although a few moderate quality studies have shown that imaging without the use of probability and D-dimer could be appropriate in the hospitalized population until further research is available. Imaging tests alone are reasonably accurate but their use without consideration of pretest probability and D-dimer results in over testing with the associated costs and risks. Many other imaging techniques, such as magnetic resonance imaging and single-photon emission computed tomography, have been studied in the diagnosis of PE, however, studies assessing their accuracy and direct comparisons to computed tomography pulmonary angiogram (CTPA) are limited. The widespread availability of CTPA and ultrasound, coupled with the potentially fatal nature of VTE, has resulted in a dramatic increase in the number of patients tested for PE and DVT, resulting in lower rates of positive tests but without a reduction in mortality rates. This increased use of diagnostic imaging could be avoided as many good quality studies have proven that algorithm-based strategies allow for rapid and safe exclusion of DVT or PE, often without diagnostic imaging. For suspected recurrent DVT, ultrasound can result in a false positive test, especially in the setting of prior DVT. The best criteria for diagnosing DVT in patients with prior DVT in the symptomatic leg are not established yet. Since ultrasound abnormalities may persist indefinitely with DVT, the criterion of vein compressibility may not distinguish patients with acute recurrent DVT from patients with chronic findings.Conclusion: The use of clinical decision rules in combination with D-dimer has standardized the diagnostic approaches for VTE. Currently, in most cases, the use of algorithmic strategies is supported by strong evidence as they allow for safe, convenient and cost-effective investigation of outpatients. However, the algorithmic strategies are less useful in hospitalized patients. Further research is also desperately needed in patients with suspected upper extremity DVT and pregnant patients. DisclosuresWells:Bayer Healthcare: Other: Speaker Fees, Ad Board Meeting, Research Funding; Itreas: Other: Writing Committee; Janssen Scientific Affairs, LLC: Consultancy; BMS: Other: Grant Support; Pfizer: Other: Grant Support; Daiichi Sankyo: Other: Speaker Fees.

Improving follow-up of incomplete lower extremity venous duplex ultrasound examinations performed for deep and superficial vein thromboses

ObjectiveA lower extremity venous duplex ultrasound (LEVDUS) examination is the standard diagnostic test to evaluate patients for lower extremity deep vein thrombosis (DVT). However, some studies will be incomplete for a variety of reasons, including patient-related factors such as pain, edema, a large leg circumference, or the presence of overlying bandages or orthopedic devices. We previously reported that the frequency of obtaining a follow-up examination after an incomplete and negative (I/N) LEVDUS examination was low but that the rates of DVT found on the follow-up studies of initially I/N LEVDUS studies were similar to the rates of DVT found with initially complete LEVDUS examinations. Therefore, we recommended process improvements to increase follow-up LEVDUS studies after an I/N LEVDUS examination. In the present study, we have described the results of appending a recommendation to obtain a follow-up LEVDUS study to preliminary and final reports of I/N LEVDUS. MethodsStarting in January 2019 through December 2019, a recommendation to obtain a repeat LEVDUS examination after an I/N study was appended to the preliminary and final reports of all I/N LEVDUS examination of patients who did not, otherwise, have an indication for anticoagulation (group 2). The patients were identified on an ongoing basis through the study period and entered into an Excel database (Microsoft Corp, Redmond, Wash). Group 2 was compared with a previously reported historic control cohort of patients identified from January 2017 to December 2017 (group 1). We compared groups 1 and 2 with respect to the frequency of the repeat studies performed within 4 weeks after an I/N LEVDUS examination and the DVT rates found from the follow-up LEVDUS examinations after an I/N LEVDUS study. ResultsOf the patients in groups 1 and 2, 187 and 229 had had I/N LEVDUS examinations, with 28% and 40.2% of group 1 and 2 studies having follow-up LEVDUS examinations (P < .01). Previously unidentified lower extremity thrombi were discovered in 21% of the group 2 follow-up examinations. Also, the rate of new thrombi detected was not different between groups 2 and 1 (historic controls; DVT, 14.3% vs 18.5% [P = .25]; SVT, 6.3% vs 3.3% [P = .15]). A definitive finding of either positive or negative for DVT and SVT with a complete examination in 50% of the group 2 patients with follow-up examinations. ConclusionsA recommendation to obtain a follow-up examination appended to the preliminary and final I/N LEVDUS reports was associated with an increased rate of follow-up examinations, which revealed many previously undetected DVTs and SVTs or had allowed for definitive exclusion of DVT.

Safety of D‐dimer testing as a stand‐alone test for the exclusion of deep vein thrombosis as compared with other strategies

Essentials The aim of deep vein thrombosis (DVT) diagnostic work-up is to maximize both safety and efficiency. We explored whether D-dimer is safe and efficient as a stand-alone test to exclude DVT. Our findings suggest it is a safe, efficient and simplified diagnostic strategy. The safety of age-adjusted D-dimer as a stand-alone test requires further investigation. SUMMARY: Background Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evaluate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods We included consecutive outpatients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥0.5μgmL-1 were referred for compression ultrasonography (CUS). In patients with a D-dimer level of <0.5μgmL-1 , no further testing was performed and anticoagulation was withheld. Patients were followed for 3months for venous thromboembolism (VTE). Results Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy-three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI]0.1-1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95%CI0.0-1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand-alone test would have necessitated 80 fewer CUS examinations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95%CI0.7-3.4%). Conclusions This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assessment in prospective outcome studies.

Safety of D-Dimer As a Stand-Alone Test for the Exclusion of Deep Vein Thrombosis Compared to Other Strategies

BackgroundTogether with clinical decision rules, D-dimer testing has long been the mainstay of diagnostic work-up of suspected deep vein thrombosis (DVT). Advantages of D-dimer measurement include wide availability, low costs and high sensitivity. Age-adjusted D-dimer cut-off values have been suggested to improve specificity of D-dimer testing, defining a positive D-dimer as age multiplied by 0.01 mg/L at or over fifty years of age. Age-adjusted cut-off values have been found to increase specificity without compromising safety in the setting of acute pulmonary embolism, but have not been extensively evaluated in DVT.In this study, we aimed to evaluate and compare the diagnostic performance of fixed versus age-adjusted D-dimer thresholds in patients with suspected DVT, as a stand-alone test or in combination with pre-test probability assessment.MethodsWe included 973 consecutive outpatients referred to Østfold Hospital, Norway, with suspected first or recurrent lower extremity DVT, between 2015 and 2017. STA®-Liatest® Plus D-Dimer assay was performed and Wells clinical score assessed in all patients. Patients with positive fixed D-dimer (≥0.5 mg/L) were referred for whole-leg compression ultrasonography (CUS), whereas patients with negative D-dimer were not, irrespective of the clinical pre-test probability. Failure rate was defined as patients with negative D-dimer at baseline remaining untreated and diagnosed with symptomatic venous thromboembolism during 3-month follow-up. We compared diagnostic indices of both D-dimer thresholds with or without initial pre-test probability assessment.ResultsDVT was diagnosed in 177 out of 973 patients (18%).The fixed D-dimer cut-off was associated with a sensitivity of 99.4% (95% CI 96.9 to 99.9%) for one diagnostic failure (0.3%) (not adjudicated as of print). Adding the Wells score would have detected this one case at a cost of 90 additional CUS examinations. Age-adjusted D-dimer as a stand-alone test was associated with 6 diagnostic failures (1.5%) for a sensitivity of 96.6% (95% CI 92.8 to 98.8%). Age-adjusted D-dimer combined with Wells score yielded a sensitivity of 99.4% (95% CI 96.9 to 99.9%), with one diagnostic failure (0.4%) and 714 patients referred for CUS.ConclusionOur results suggest that the fixed D-dimer as a stand-alone test without Wells score is a safe and efficient diagnostic strategy. Combining age-adjusted D-dimer with Wells score was equally safe, but was not associated with a lower number of necessary CUS examinations. DisclosuresFronas:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant in conducting the study. Tøvik Jørgensen:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant for conducting the study. Ghanima:Bayer, BMS, Novartis: Research Funding; Amgen, Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Safe Exclusion of Deep Vein Thrombosis by a Rapid Sensitive ELISA D-dimer and Compression Ultrasonography in 1330 Outpatients With Suspected DVT

Of 1330 outpatients with suspected deep vein thrombosis (DVT), a normal enzyme-linked immunosorbent assay (ELISA) d-dimer (VIDAS) of <500 ng/mL was true negative in 382 of 384 and false negative in compression ultrasonography (CUS) in 2, indicating a sensitivity of 99.52% and a negative predictive value (NPV) of 99.48%, with a specificity of 36% irrespective of clinical score. In 1059 outpatients with no DVT, the CUS was positive for the alternative diagnoses (AD): Bakers cyst, muscle hematoma, or old DVT in 62 (5.8%); superficial vein thrombosis without DVT in 78 (7.4%), and leg edema or varices in 17%. A second CUS in 641 patients was positive in 26 (4.0%), indicating an NPV of 96% after a first negative CUS. The NPV of the combination of a negative first CUS and a ELISA d-dimer test <1000 ng/mL was 99.1% at a specificity of 66.9%. As this strategy is cost effective by reduction in the need to repeat CUS by 67%, we designed a novel algorithm for the safe exclusion and diagnosis of DVT and AD for subsequent evaluation in a large prospective study.

Complete Compression Ultrsonography, Clinical Score, Underlying Risk

Superficial vein thrombosis is an integral part of venous thromboembolism (VTE) together with deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of SVT is 1.6 per 1000 persons per year. The incidence of DVT is about 1.0 per 1000 persons per year in the general population, 1.8 per 1000 persons per year at age 65 to 69 years and 3.1 per 1000 persons per year at age 85 to 89 years. First episodes of DVT are in two-thirds of cases elicited by risk factors, including varicose veins, cancer, pregnancy/ postpartum, oral contraceptives below the age of 50 years, immobility or surgery. Pain and tenderness in the calf and popliteal fossa may occur resulting from other conditions labeled as alternative diagnosis (AD) including Baker’s cyst, ruptured Baker’s cyst, torn plantaris tendon, hematoma, or muscle tears or pulls. The requirement for a safe diagnostic strategy of deep vein thrombosis (DVT) should be based on an objective post-test incidence of venous thromboembolism (VTE) of less than 0.1% with a negative predictive value for exclusion of DVT of 99.99% during 3 months follow-up. Modification of the Wells score by elimination of the “minus 2 points” for AD is mandatory and will improve clinical score assessment for DVT suspicion in the primary care and outpatient medical diagnostic setting. Compression ultrasonography (CUS) for proximal DVT overlooks distal DVT and is not cost-effective enough to rule in or out DVT. Complete CUS (CCUS) does pick up alternative diagnoses (AD) like Bakers cyst, muscle hematomas, old DVT, and superficial vein thrombosis (SVT). ADs with a negative CCUS include leg edema, varices erysipelas are easily picked up by physical examination. The sequential use of CCUS followed by quantitative rapid ELISA-D-dimer testing and modified Wells’ clinical score assessment is cost-effective and objective diagnostic algorithm that can safely and effectively exclude and diagnose both DVT and AD in patients with suspected DVT. About 10 to 30% of patients with DVT develop overt PTS (CEAP, C4,5) at one year post-DVT. DVT has a recurrence rate of about 20% to 30% after 5 years. A scoring system for lower extremity venous thrombosis (LET) extension on CCUS related to therapeutic implications is presented to prevent DVT recurrence and the post-thrombotic syndrome (PTS).

Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis

Objective To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients.Design Meta-analysis of individual patient data. Data...

A New D-dimer Cutoff Value to Improve the Exclusion of Deep Vein Thrombosis in Cancer Patients

To find a more appropriate alternative to D-dimer cutoff value for the diagnosis of deep vein thrombosis (DVT) in cancer patients. A total of 711 cancer patients with symptoms suspicious of DVT were included in the study. D-dimer levels were assessed using ELISA. All patients were subjected to imaging procedures. Among 711 patients with cancer, 466 (65.5%) were females and 245 (34.5%) were males, with an average age of 57.3 ± 13.23 years. The mean age in the DVT group was significantly higher than in the non-DVT group (P<0.05). The D-dimer levels of the DVT group were significantly higher than those of the non-DVT group (P<0.05). The incidence rate of DVT varied significantly according to cancer type (P<0.05). Increasing age and lung cancer were significantly correlated with D-dimer levels (P<0.05), and a one-year increase in age was associated with a 14.28 ng/ml increase in the D-dimer value. The optimal cutoff point for D-dimer was found to be 981 ng/ml, with a sensitivity of 86.4%, specificity of 79.4%, and accuracy of 82.6%. If the D-dimer cutoff point was set to 981 ng/ml, the specificity would increase from 61.8% to 85.5% without loss of sensitivity in patients aged 40 years or younger. In patients aged more than 40 years, the new cutoff almost doubled the specificity with slightly reduced sensitivity. In cancer patients, a new cutoff value of 981 ng/ml effectively improved the exclusion of DVT, especially for patients aged more than 40 years.

Single whole‐leg compression ultrasound for exclusion of deep vein thrombosis in symptomatic ambulatory patients: a prospective observational cohort study

International guidance has recently recommended serial proximal compression ultrasound (CUS) as first line imaging for suspected deep vein thrombosis (DVT). Single whole-leg CUS is a routine alternative diagnostic strategy that can reduce repeated attendances and identify alternative pathology. We conducted a prospective observational cohort study. Consecutive ambulatory, adult patients with suspected DVT and negative or inconclusive whole-leg CUS had anticoagulation withheld and were followed for 3months. The primary outcome was a predefined clinically relevant adverse event rate. Secondary outcomes included technical failure, alternative diagnoses and all cause mortality. 212 patients agreed to participate and completed follow up. One patient was subsequently diagnosed with an isolated distal DVT. The adverse event rate was thus 1/212, 0·47% (95% confidence interval [CI] 0·08-2·62). Technical imaging failure occurred in 11·3% of cases (95% CI 7·7-16·3). Several potential predictors of an inconclusive result were identified on multivariate analysis. 150 (70·8%) patients were provided with a documented alternative diagnosis. Patients who have anticoagulation withheld following a negative or inconclusive whole-leg CUS for suspected DVT have a low rate of adverse events. Technical failure remains an issue: several factors were significantly associated with inconclusive results and may warrant an alternative diagnostic approach.

Limited diagnostic value of Wells-score and D-dimer testing in hospitalized dermatologic patients with symptoms of deep vein thrombosis

D-dimer analysis and clinical probability scoring (Wells-score) show a high sensitivity and negative predictive value for the exclusion of deep vein thrombosis (DVT). To identify the diagnostic performance of D-dimer testing and Wells-score in hospitalized patients with dermatologic conditions. In this retrospective cohort study, 109 examinations in 102 patients were performed by Wells-score, Tina-quant D-dimer testing and whole-leg duplex ultrasonography or phlebography. DVT was confirmed in 14 patients. The Wells-score alone allowed no discrimination of DVT and non-DVT patients. D-dimer testing identified all cases of DVT (100% sensitivity). Only 16 patients showed D-dimers within normal limits and none was diagnosed with DVT (100% negative predictive value). A high rate of false-positive D-dimer results (72%) led to a low specificity (17%). The number needed-to-test to exclude one DVT was 6.8. Based on multivariate statistical analysis, increased D-dimer levels were significantly associated with the dermatologic main diagnosis (p = 0.008), age (p = 0.001) and with the presence of DVT (p = 0.011). The highest D-dimer values were found in non-DVT patients with metastasized or systemic malignancies (median 2.48 mg/L) or inflammatory skin conditions (e.g., generalized psoriasis, median 2.22 mg/L). Wells-score and D-Dimer testing were of limited diagnostic value because of many false-positive results. Required imaging procedures were reduced by only 16 cases (15%). Therefore, we suggest directly investigating hospitalized dermatologic patients with suspected DVT and skin diseases associated with high D-Dimer levels, by whole-leg compression ultrasonography.

Diagnosis and treatment of superficial vein thrombosis

Superficial vein thrombosis (SVT) is a common disease, characterized by an inflammatory-thrombotic process in a superficial vein. Typical clinical findings are pain and a warm, tender, reddish cord along the vein. Until recently, no reliable epidemiological data were available. The incidence is estimated to be higher than that of deep-vein thrombosis (DVT) (1/1000). SVT shares many risk factors with DVT, but affects twice as many women than men and frequently occurs in varicose veins. Clinically, SVT extension is commonly underestimated, and patients may have asymptomatic DVT. Therefore, ultrasound assessment and exclusion of DVT is essential. Risk factors for concomitant DVT are recent hospitalization, immobilization, autoimmune disorders, age > 75 years, prior VTE, cancer and SVT in non-varicose veins. Even though most patients with isolated SVT (without concomitant DVT or PE) are commonly treated with anticoagulation for a median of 15 days, about 8% experience symptomatic thromboembolic complications within three months. Risk factors for occurrence of complications are male gender, history of VTE, cancer, SVT in a non-varicose vein or SVT involving the sapheno-femoral junction (SFJ). As evidence supporting treatment of isolated SVT was sparse and of poor quality, the large, randomized, double-blind, placebo-controlled CALISTO trial was initiated assessing the effect of fondaparinux on symptomatic outcomes in isolated SVT. This study showed that, compared with placebo, 2.5 mg fondaparinux given for 45 days reduced the risk of symptomatic thromboembolic complications by 85% without increasing bleeding. Based on CALISTO and other observational studies, evidence-based recommendations can be made for the majority of SVT patients. Further studies can now be performed in higher risk patients to address unresolved issues.

Comparison of empirical estimate of clinical pretest probability with the Wells score for diagnosis of deep vein thrombosis

Wells score has been validated for estimation of pretest probability in patients with suspected deep vein thrombosis (DVT). In clinical practice, many clinicians prefer to use empirical estimation rather than Wells score. However, which method is better to increase the accuracy of clinical evaluation is not well understood. Our present study compared empirical estimation of pretest probability with the Wells score to investigate the efficiency of empirical estimation in the diagnostic process of DVT. Five hundred and fifty-five patients were enrolled in this study. One hundred and fifty patients were assigned to examine the interobserver agreement for Wells score between emergency and vascular clinicians. The other 405 patients were assigned to evaluate the pretest probability of DVT on the basis of the empirical estimation and Wells score, respectively, and plasma D-dimer levels were then determined in the low-risk patients. All patients underwent venous duplex scans and had a 45-day follow up. Weighted Cohen's κ value for interobserver agreement between emergency and vascular clinicians of the Wells score was 0.836. Compared with Wells score evaluation, empirical assessment increased the sensitivity, specificity, Youden's index, positive likelihood ratio, and positive and negative predictive values, but decreased negative likelihood ratio. In addition, the appropriate D-dimer cutoff value based on Wells score was 175 μg/l and 108 patients were excluded. Empirical assessment increased the appropriate D-dimer cutoff point to 225 μg/l and 162 patients were ruled out. Our findings indicated that empirical estimation not only improves D-dimer assay efficiency for exclusion of DVT but also increases clinical judgement accuracy in the diagnosis of DVT.

Positive Predictive Value of Progressively Elevated D-Dimer Levels in Patients with a Suspected First Deep Vein Thrombosis.

AbstractAbstract 2258 BackgroundD-dimer is nearly always increased in patients with acute venous thromboembolism (VTE) and, therefore, a low value (i.e., negative test) has high negative predictive value. A positive result indicates the need for further diagnostic testing (e.g. ultrasound imaging if deep vein thrombosis is suspected), but it is generally believed that the predictive value of a positive result is of no clinical value. While this is true if D-dimer values are dichotomized as positive or negative, D-dimer may have diagnostically useful positive predictive value when levels are markedly elevated (i.e., positive results are not considered as a single category). ObjectiveTo determine the prevalence of, and likelihood ratios for, deep vein thrombosis (DVT) associated with progressively elevated D-dimer levels in patients with a suspected first DVT. MethodsWe performed a retrospective analysis of D-dimer level from 1224 banked peripheral blood samples from participants enrolled at 4 of the 5 participating clinical centres in the recently competed SELECT study, which compared two diagnostic strategies in patients with a suspected first DVT. D-dimer levels were measured using the Triage® D-dimer assay. The clinical pretest probability (CPTP) was determined in all patients using the 9 point Wells score and categorized as low, moderate or high. Patients were categorized as DVT positive if DVT was diagnosed by lower limb ultrasound (US) at initial presentation or VTE was diagnosed during three months of follow-up. Patients were categorized as DVT negative if DVT was not diagnosed at initial assessment (patients with low CPTP and negative D-dimer results did not undergo US) and there was no VTE during three months of follow-up. The diagnosis or exclusion of DVT was made independently of the Triage® D-dimer measurements (a different D-dimer assay was used at presentation in the SELECT study, and D-dimer was not used to evaluate suspected VTE during the 3 month follow-up).The prevalence of DVT and likelihood ratios (LHR) for all patients, and according to CPTP (low, moderate or high), was determined for the following intervals of D-dimer level: <500ug/L, 500–1000ug/L, 1001–1500ug/L, 1501–2000ug/L, 2001–3000 ug/L, 3001–4000ug/L, 4001ug/L-5000ug/L and >5000ug/L. ResultsThe prevalence of DVT, and associated LHR, among all patients increased steadily with rising D-dimer levels (Table 1). At values of less than 1000ug/L, the prevalence of DVT among all patients was low (0.15% for D-dimer <500ug/L and 1.2% for 500–1000ug/L). However, at levels above 1500ug/L there was a progressive increase in the prevalence from 14.3% for 1500–2000ug/L to 64.0% at levels >5000ug/L. The associated likelihood ratios for DVT also increased according to D-dimer level from 2.6 for levels of 1500–2000ug/L to 28.0 for values >5000ug/L.The prevalence of DVT was 2.6% for patients with low CPTP, 6.0% among those with moderate CPTP and 22.0% among patients with high CPTP. The increase in prevalence and associated LHR for DVT with increasing D-dimer levels was consistent across all three CPTP groups. ConclusionIncreasing D-dimer levels are associated with a progressive increase in prevalence and LHR for DVT across all clinical pretest probability strata. The positive predictive value of markedly elevated D-dimer levels was high and may help to identify the subgroup of patients with an abnormal D-dimer level who require more intensive investigation after a normal imaging test.Table 1-Prevalence and Likelihood Ratio associated with different D-dimer levelsD-dimer (ug/L)All patientsLow CPTPModerate CPTPHigh CPTPPrev (%)LHRPrev (%)LHRPrev (%)LHRPrev (%)LHR<5000.150.02000.40.0600500-10001.20.20000.90.15110.441001-15005.00.824.61.74.40.738.30.321501-2000142.6145.6173.2002001-3000193.7156.2203.2251.23001-4000286.12311265.5503.44001-5000306.9209275.9432.7>50006428432756208928Prev, prevalence; LHR, likelihood ratio; CPTP, clinical pretest probability Disclosures:Bates:Trinity Biotech: Consultancy, consultation fees and in-kind support (D-dimer kits) Other. Kearon:Alere: Consultancy.

Accuracy in diagnosing deep and pelvic vein thrombosis in primary care: an analysis of 395 cases seen by 58 primary care physicians.

Ruling out a deep vein thrombosis (DVT) is difficult in general practice because the clinical manifestations of DVT are nonspecific and more often due to other diseases. The aim of diagnostic screening in primary care must be to rule out a DVT with high accuracy in most patients, so that only those who are likely to have a DVT will undergo further testing. In this study, we tested the accuracy of exclusion of DVT by the combination of a clinical score (the Wells score) with either a bedside D-dimer test or selective compression sonography. This cohort study included all patients who presented to the participating primary care physicians and were suspected of having a DVT on the basis of pre-defined inclusion criteria. To rule out DVT, a Wells score was determined for all patients, and all patients additionally underwent either a D-dimer test or selective compression sonography as required by the clinical algorithm. Patients were seen six weeks later in follow-up to determine whether they had actually had a DVT (gold standard). The negative predictive value (NPV) for the exclusion of DVT in this way was determined, as was the NPV of clinical judgment alone, without knowledge of Wells score or D-dimer results. 395 patients were evaluated by 58 primary care physicians for suspected DVT; 59 were ultimately found to have had a definite DVT, and 9 a probable DVT. Exclusion of DVT with the study protocol had an NPV of 99.0% (95% CI, 96.3 to 99.8)-i.e. only one case of DVT in 100 patients was missed (maximum: 4, minimum: 0)-while clinical judgment alone had an NPV of 95.0% (95% CI, 90.7 to 97.7). We recommend the Wells score combined with either a D-dimer test or selective compression sonography according to the algorithm used in this study for use in primary care to rule out DVT. Clinical judgment alone is less effective.