scholarly journals Diagnostic Accuracy of D-Dimer for Pulmonary Embolism and Lower Limb Deep Vein Thrombosis Testing in People with Cancer: A Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3218-3218
Author(s):  
Kerstin De Wit ◽  
Sameer Parpia ◽  
Adam Sunavsky ◽  
Aleksandrija Ilic ◽  
Federico Germini ◽  
...  

Abstract Introduction There are evidence-based protocols for the diagnosis and exclusion of pulmonary embolism (PE) and deep vein thrombosis (DVT) which include clinical probability scoring along with selective D-dimer testing and diagnostic imaging. D-dimer assessment in VTE (venous thromboembolism) testing tends to be omitted in patients with cancer, partly because of perceived D-dimer lack of sensitivity and specificity. The aim of this systematic review and meta-analysis was to report the diagnostic accuracy of D-dimer for PE and lower limb DVT in patients with cancer. This study was part of a research program to set International Society of Thrombosis and Haemostasis standards for VTE testing in patients with cancer. Methods This systematic review and meta-analysis followed the MOOSE guidelines and was registered in PROSPERO, CRD42020181007. We searched Medline via OVID from conception to 12 th March 2020 for diagnostic PE and DVT studies reporting on people with cancer, or a subgroup of people with cancer. Researchers in the field were contacted for information on unpublished studies. All languages were included. Two researchers screened the titles and abstracts. Four researchers reviewed the selected full texts to determine which studies fulfilled inclusion criteria. Two researchers assessed risk of bias using QUADAS-2, extracted data on the true positive, false positive, true negative and false negative results for D-dimer alone, and D-dimer combined with clinical probability estimation. We used the bivariate random effects method to meta-analyze sensitivity and specificity values. We used a random effects model to estimate pooled false negative rates and efficiency for combining a negative D-dimer (manufacturer recommended cutoff) with a low clinical probability to exclude PE or DVT in patients with cancer. Results were displayed on a Forest plot. Heterogeneity was assessed using I 2. Results From 7947 titles and abstracts, we reviewed 49 full text manuscripts, including 13 studies for analysis. Risk of bias was low across all domains for only 5/13 studies. Figures 1 shows the Forest plots grouped by sensitivity and specificity for PE and DVT. The pooled estimates for D-dimer in the diagnosis of VTE in cancer patients (regardless of clinical probability) were 96.4% (95% confidence interval (CI) 94.8 to 97.5%) sensitivity and 26.4% (95% CI 18.1 to 37.0%) specificity. For PE, D-dimer was 96.9% (96.1 to 97.5%) sensitive (I 2 0%, N=2,299) and 14.0% (12.1 to 16.0%) specific, (I 2 69%, N=11,455). For DVT, D-dimer was 94.3% (89.8 to 97.6%) sensitive, (I 2 61%, N=546) and 46.4% (39.8 to 53.3%) specific, (I 2 59%, N=724). The efficiency of combining a low D-dimer (using the manufacturer recommended cutoff) and low clinical probability to exclude DVT or PE was 9.3%, (95% CI 6.9 to 11.9%), N=1,347. There were only 122 patients in the false negative rate analysis of whom 1 patient was diagnosed with VTE in follow up. A pooled analysis was not performed for the false negative rate. Conclusions D-dimer is a sensitive test for both PE and lower limb DVT in people who have cancer. Approximately 10% of patients with cancer and suspected VTE can have VTE excluded with D-dimer and clinical probability prior to ordering diagnostic imaging. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S27-S27
Author(s):  
S. Sharif ◽  
C. Kearon ◽  
M. Eventov ◽  
P. Sneath ◽  
M. Li ◽  
...  

Introduction: Diagnosing deep vein thrombosis (DVT) is of critical importance because of its associated morbidity and mortality. Diagnosing DVT can be challenging in the Emergency Department (ED) due to inconsistent adherence to, and utilization of the Wells rule. Both the age-adjusted and clinical probability adjusted D-dimer have been shown to decrease ultrasound (US) utilization rates. We aimed to compare the safety and efficacy of the Wells score with D-dimer to the age-adjusted and clinical probability-adjusted D-dimer in Canadian ED patients tested for DVT. Methods: This was a health records review of ED patients investigated for DVT at two EDs over a two-year period. Inclusion criteria were ED physician ordered duplex ultrasonography or D-dimer for investigation of lower limb DVT. Patients under the age of 18 were excluded. DVT was considered to be present during the ED visit if DVT was diagnosed on duplex ultrasonography and was treated for acute DVT, or if the patient was subsequently diagnosed with pulmonary embolism (PE) or DVT during the next 30 days. Trained researchers extracted anonymized data. The Wells D-dimer, age-adjusted D-dimer, and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of duplex ultrasonography imaging and the false negative rate was calculated for each rule. Results: Between April 1st 2013 and March 31st 2015, there were 1,198 patients tested for DVT. Of the low and moderate clinical pretest probability patients (Wells score ≤ 2), only 436 had a D-Dimer test and were eligible for our analysis. The average age of the patients was 59, 56% were female, and 4% had a malignancy. 207/436 patients (47.4%, 95%CI 42.8-52.2%) would have had US imaging for DVT if the age-adjusted D-dimer rule was used. 214/436 patients (49.1%, 95%CI 44.4-53.8%) would have had imaging for DVT if the clinical probability-adjusted D-dimer was used. If the Wells rule was used with the standard D-dimer cutoff of 500, 241/436 patients (55.2%, 95%CI 50.6-59.9%) would have had imaging for DVT. The false-negative rate for the Wells rule was 1.5% (95%CI 0.5-4.4%). The false-negative rate for the age-adjusted D-dimer rule was 1.3% (95%CI 0.4-3.8%). The false-negative rate for the clinical-probability adjusted D-Dimer was 1.8% (95%CI 0.7-4.5%). Conclusion: In comparison with the approach of the Wells score and D-dimer, both the age-adjusted and clinical probability-adjusted D-dimer diagnostic strategies could reduce the proportion of patients who require US imaging.


2017 ◽  
Vol 33 (7) ◽  
pp. 458-463 ◽  
Author(s):  
Efrem Gómez-Jabalera ◽  
Sergio Bellmunt Montoya ◽  
Eva Fuentes-Camps ◽  
José Román Escudero Rodríguez

Objective In the diagnosis of deep vein thrombosis, new D-dimer cut-off values were defined by multiplying 10 µg/L × age. The objective of the present study is to define a more specific age-adjusted value, including the pre-test Wells score, without worsening sensitivity. Methods We designed a case–control study in patients attended in the emergency department with clinically suspected deep vein thrombosis. Demographics, Wells score, D-dimer and ultrasound data were collected. In low and intermediate clinical probability cases for deep vein thrombosis, we determined the specificity and sensitivity (false-negative rates) for the following cut-off values of D-dimer: age × 10 µg/L, age × 15 µg/L, age × 20 µg/L, age × 25 µg/L and age × 30 µg/L. The cut-off value with maximum specificity without any false-negative result (sensitivity 100%) was identified. Results We included 138 consecutive patients, 39.9% were men and the mean age was 71.6 years. Deep vein thrombosis was diagnosed in 16.7% of patients and the Wells score was low in 69.6%, intermediate in 21% and high in 9.4% of patients. Applying the conventional cut-off value of 500 µg/L, the specificity was 21.1% with a sensitivity of 100%. Maintaining 100% sensitivity, the highest specificity was reached with a cut-off value for D-dimer equivalent to the age × 25 µg/L in low-risk patients (67.1% specificity) and the age × 10 µg/L (50% specificity) in intermediate-risk patients. Conclusions In patients with low Wells score, the cut-off value can be raised to age × 25 µg/L in order to rule out deep vein thrombosis without jeopardizing safety. In intermediate-risk patients, the D-dimer cut-off value could be raised to age × 10 µg/L as previously suggested.


CJEM ◽  
2018 ◽  
Vol 20 (S1) ◽  
pp. S105-S105 ◽  
Author(s):  
S. Sharif ◽  
C. Kearon ◽  
M. Eventov ◽  
M. Li ◽  
R. Jiang ◽  
...  

Introduction: Diagnosing pulmonary embolism (PE) can be challenging because the signs and symptoms are often non-specific. Studies have shown that evidence-based algorithms are not always adhered to in the Emergency Department (ED) and are often not used correctly, which leads to unnecessary CT scanning. The YEARS diagnostic algorithm, consisting of three items (clinical signs of deep vein thrombosis, hemoptysis, and whether pulmonary embolism is the most likely diagnosis) and D-dimer, is a novel and simplified way to approach suspected acute PE. The purpose of this study was to 1) evaluate the use of the YEARS algorithm in the ED and 2) to compare the rates of testing for PE if the YEARS algorithm was used. Methods: This was a health records review of ED patients investigated for PE at two emergency departments over a two-year period (April 2013-March 2015). Inclusion criteria were ED physician ordered CT pulmonary angiogram, ventilation-perfusion scan, or D-dimer for investigation of PE. Patients under the age of 18 and those without a D-dimer test were excluded. PE was considered to be present during the emergency department visit if PE was diagnosed on CT or VQ (subsegmental level or above), or if the patient was subsequently found to have PE or deep vein thrombosis during the next 30 days. Trained researchers extracted anonymized data. The rate of CT/VQ imaging and the false negative rate was calculated. Results: There were 1,163 patients that were tested for PE and 1,083 patients were eligible for our analysis. Of the total, 317/1,083 (29.3%; 95%CI 26.6-32.1%) had CT/VQ imaging for PE, and 41/1,083 (3.8%; 95%CI 2.8-5.1%) patients were diagnosed with PE at baseline. Three patients had a missed PE, resulting in a false negative rate of 0.4% (95%CI 0.1-1.2%). If the YEARS algorithm was used, 211/1,083 (19.5%; 95%CI 17.2-22.0%) would have required imaging for PE. Of the patients who would not have required imaging according to the YEARS algorithm, 8/872 (0.9%; 95%CI 0.5-1.8%) would have had a missed PE. Conclusion: If the YEARS algorithm was used in all patients with suspected PE, fewer patients would have required imaging with a small increase in the false negative rate.


2004 ◽  
Vol 91 (01) ◽  
pp. 187-195 ◽  
Author(s):  
Daniel Colombier ◽  
Gérard Victor ◽  
Marie Elias ◽  
Catherine Arnaud ◽  
Henri Juchet ◽  
...  

SummaryA limited ultrasound (US) confined to the popliteal and femoral veins is usually performed to detect deep vein thrombosis (DVT) in patients with clinically suspected acute pulmonary embolism (PE). Our objective was to assess the diagnostic accuracy of complete lower limb US examining both the proximal and distal veins in this setting. In this prospective study, 210 consecutive patients were included. Complete US was performed by independent operators and compared blindly with a reference strategy combining clinical probability, ventilation perfusion scan and pulmonary angiography to a three-month clinical follow-up. Simultaneously,VIDAS D-dimer (DD) assay and helical computed tomography (HCT) of the lungs were assessed independently and blindly. PE was present in 74 patients (35%). Complete US detected DVT in 91 patients (43%), proximal in 51 and distal in 40. Sensitivity and specificity with a 0.95 confidence interval were respectively 0.93 [0.85 – 0.97] and 0.84 [0.77 – 0.89]. Limited US detected DVT in only 46 patients (22%). Sensitivity and specificity were respectively 0.55 [0.44 – 0.66] and 0.96 [0.92 – 0.98]. For DD they were 0.92 [0.83 – 0.96] and 0.24 [0.17 – 0.32] and for HCT 0.84 [0.73 – 0.90] and 0.87 [0.80 – 0.92]. Complete lower limb US has higher sensitivity and capacity to exclude PE than limited US, but a slightly lower specificity. Complete US results also compared favourably with those of HCT and DD.The utility of including this method in diagnostic strategies for PE needs to be assessed in cost-effectiveness analysis and in outcome studies.


2021 ◽  
Vol 10 (7) ◽  
pp. 1543
Author(s):  
Morwenn Le Boulc’h ◽  
Julia Gilhodes ◽  
Zara Steinmeyer ◽  
Sébastien Molière ◽  
Carole Mathelin

Background: This systematic review aimed at comparing performances of ultrasonography (US), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (PET) for axillary staging, with a focus on micro- or micrometastases. Methods: A search for relevant studies published between January 2002 and March 2018 was conducted in MEDLINE database. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies checklist. Sensitivity and specificity were meta-analyzed using a bivariate random effects approach; Results: Across 62 studies (n = 10,374 patients), sensitivity and specificity to detect metastatic ALN were, respectively, 51% (95% CI: 43–59%) and 100% (95% CI: 99–100%) for US, 83% (95% CI: 72–91%) and 85% (95% CI: 72–92%) for MRI, and 49% (95% CI: 39–59%) and 94% (95% CI: 91–96%) for PET. Interestingly, US detects a significant proportion of macrometastases (false negative rate was 0.28 (0.22, 0.34) for more than 2 metastatic ALN and 0.96 (0.86, 0.99) for micrometastases). In contrast, PET tends to detect a significant proportion of micrometastases (true positive rate = 0.41 (0.29, 0.54)). Data are not available for MRI. Conclusions: In comparison with MRI and PET Fluorodeoxyglucose (FDG), US is an effective technique for axillary triage, especially to detect high metastatic burden without upstaging majority of micrometastases.


2016 ◽  
Vol 23 (3) ◽  
pp. 221-228 ◽  
Author(s):  
Cristina Legnani ◽  
Michela Cini ◽  
Mirella Frascaro ◽  
Giuseppina Rodorigo ◽  
Michelangelo Sartori ◽  
...  

In patients presenting non-high clinical pretest probability (PTP), a negative d-dimer can exclude venous thromboembolism without imaging tests. However, each d-dimer assay should be validated in prospective studies. We evaluated an automated d-dimer immunoassay using the Sclavo Auto d-dimer (Sclavo Diagnostics Int, Sovicille, Italy) provided by Dasit Diagnostica (Cornaredo, Milan, Italy). Three hundred two consecutive outpatients suspected of leg deep vein thrombosis (DVT) with non-high PTP were included. The Sclavo Auto d-dimer assay was evaluated on 2 analyzers (Sysmex CA-7000 and Sysmex CS-2100; Sysmex Corporation, Kobe, Japan, provided by Dasit). The cutoff value (200 ng/mL) was established a priori. Prevalence of DVT was 11.9%. Since no false-negative patients were detected, the sensitivity and negative predictive values (NPVs) were 100% (sensitivity = CA-7000: 100% [95% confidence interval, CI: 93.3-100], CS-2100: 100% [95% CI: 93.3-100]; NPV = CA-7000: 100% [95% CI: 97.9-100], CS-2100: 100% [95% CI: 98.0-100]). Specificity was 65.4% (95% CI: 59.4-71.1) and 69.2% (95% CI: 63.3-74.7) for CA-7000 and CS-2100, respectively. Specificity increased when a higher cutoff value (234 ng/mL) was used for patients aged ≥60 years without compromising the safety. Assay reproducibility was satisfactory at concentrations near the cutoff value (total coefficient of variations <10%). In conclusion, the Sclavo Auto d-dimer assay was accurate when used for DVT diagnostic workup in outpatients with non-high PTP. Based on its high sensitivity and NPV, it can be used as a stand-alone test in outpatients with non-high PTP. Given its high specificity, the number of patients in whom further imaging techniques can be avoided increased, improving the yield of the test.


2012 ◽  
Vol 107 (02) ◽  
pp. 369-378 ◽  
Author(s):  
Jan Schwonberg ◽  
Carola Hecking ◽  
Marc Schindewolf ◽  
Dimitrios Zgouras ◽  
Susanne Lehmeyer ◽  
...  

SummaryThe diagnostic value of D-dimer (DD) in the exclusion of proximal deep-vein thrombosis (DVT) is well-established but is less well-known in the exclusion of distal (infrapopliteal) DVT. Therefore, we evaluated the diagnostic abilities of five DD assays (Vidas-DD, Liatest-DD, HemosIL-DD, HemosIL-DDHS, Innovance-DD) for excluding symptomatic proximal and distal leg DVT. A total of 243 outpatients whose symptoms were suggestive of DVT received complete compression ultrasonography (cCUS) of the symptomatic leg(s). The clinical probability of DVT (PTP) was assessed by Wells score. Thirty-eight proximal and 31 distal DVTs (17 tibial/fibular DVTs, 14 muscle DVTs) were diagnosed by cCUS. Although all assays showed high sensitivity for proximal DVT (range 97–100%), the sensitivity was poor for distal DVT (range 78–93%). None of the assays were individually able to rule out all DVTs as a stand-alone test (negative predictive value [NPV] 91–96%). However, a negative DD test result combined with a low PTP exhibited a NPV of 100% for all DVTs (including proximal, tibial/fibular, and muscle DVTs) with the HemosIL-DDHS and Innovance-DD. All proximal and tibial/fibular DVTs, but not all muscle DVTs, could be ruled out with this strategy using the Liatest-DD and Vidas-DD. The HemosIL-DD could not exclude distal leg DVT, even in combination with a low PTP. The combination of a negative DD with a low PTP showed a specificity of 32–35% for all DVTs. In conclusion, our study shows that when used in conjunction with a low PTP some DD assays are useful tools for the exclusion of distal leg DVT.


1991 ◽  
Vol 6 (4) ◽  
pp. 241-248 ◽  
Author(s):  
Håkan Ahlström ◽  
Stefan Nilsson ◽  
Göran Hellers

One-hundred-and-eleven consecutive patients who were referred for routine phlebography because of clinically suspected deep vein thrombosis (DVT) were also investigated with a new, simplified, computerized strain-gauge plethysmograph (Phlebotest, Eureka AB). An occlusion plethysmograph curve was obtained from each leg simultaneously. Four different numerical parameters were defined and determined from this curve. These parameters were correlated with the phlebographic diagnosis. Three of the parameters of the plethysmograph curve correlated well with the phlebographic diagnosis, which proved correct in 54 patients without DVT, including two false negative cases, and in 12 patients with thrombosis. In 45 patients, plethysmography alone was not sufficient to establish a diagnosis. The plethysmograph described is easy to handle and is suggested for use in selecting those patients, with or without thrombosis, who do not require supplementary phlebography.


CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S116
Author(s):  
S. Sharif ◽  
C. Kearon ◽  
M. Li ◽  
M. Eventov ◽  
R. Jiang ◽  
...  

Introduction: Diagnosing pulmonary embolism (PE) in the emergency department can be challenging due to non-specific signs and symptoms; this often results in the over-utilization of CT pulmonary angiography (CT-PA). In 2013, the American College of Chest Physicians identified CT-PA as one of the top five avoidable tests. Age-adjusted D-dimer has been shown to decrease CT utilization rates. Recently, clinical-probability adjusted D-dimer has been promoted as an alternative strategy to reduce CT scanning. The aim of this study is to compare the safety and efficacy of the age-adjusted D-dimer rule and the clinical probability-adjusted D-dimer rule in Canadian ED patients tested for PE. Methods: This was a retrospective chart review of ED patients investigated for PE at two hospitals from April 2013 to March 2015 (24 months). Inclusion criteria were the ED physician ordered CT-PA, Ventilation-Perfusion (VQ) scan or D-dimer for investigation of PE. Patients under the age of 18 were excluded. PE was defined as CT/VQ diagnosis of acute PE or acute PE/DVT in 30-day follow-up. Trained researchers extracted anonymized data. The age-adjusted D-dimer and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of CT/VQ imaging and the false negative rates were calculated. Results: In total, 1,189 patients were tested for PE. 1,129 patients had a D-dimer test and a Wells score less than 4.0. 364/1,129 (32.3%, 95%CI 29.6-35.0%) would have undergone imaging for PE if the age-adjusted D-dimer rule was used. 1,120 patients had a D-dimer test and a Wells score less than 6.0. 217/1,120 patients (19.4%, 95%CI 17.2-21.2%) would have undergone imaging for PE if the clinical probability-adjusted D-dimer rule was used. The false-negative rate for the age-adjusted D-dimer rule was 0.3% (95%CI 0.1-0.9%). The false-negative rate of the clinical probability-adjusted D-dimer was 1.0% (95%CI 0.5-1.9%). Conclusion: The false-negative rates for both the age-adjusted D-dimer and clinical probability-adjusted D-dimer are low. The clinical probability-adjusted D-dimer results in a 13% absolute reduction in CT scanning compared to age-adjusted D-dimer.


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