Underwent D-dimer Testing Research Articles

Prospective Evaluation of the Prevalence of Pulmonary Embolism in Patients with Chronic Obstructive Pulmonary Disease Exacerbation: Challenges and Feasibility

Introduction: Data on the prevalence of pulmonary embolism (PE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in North America is lacking, with most of the prospective studies conducted in Europe and Asia. The aim of this study is to describe feasibility of prospective collection of data evaluating the prevalence of PE in patients admitted for AECOPD in Canada, and to describe challenges of this approach. Methods: This is a secondary analysis of a prospective pilot patient cohort aiming to assess the diagnosis of AECOPD among hospitalized patients. Items of the Wells PE and revised Geneva scores were prospectively collected. All patients underwent D-dimer testing within 24 hours of admission. All patients were followed for 3 months. Feasibility outcomes were prospective data collection to evaluate the prevalence of PE, D-dimer level measurement and 3-month follow-up. The study was considered feasible if >=90% of the patients had prospective data collected to assess the prevalence of PE, >=80% of the patients had D-dimer level measured and their 3-month follow-up, respectively. Challenges were also assessed. Results: Twenty patients were included. According to the Wells PE score, 16 (80.0%), 4 (20.0%) and 0 (0.0%) patients had low, moderate and high clinical pre-test probability (c-PTP), respectively. According to the revised Geneva score, 2 (10.0%), 17 (85.0%) and 1 (5.0%) patients had low, intermediate and high c-PTP, respectively. Based on age-adjusted D-dimer cut-off, 7 and 11 patients had negative and positive D-dimer, respectively. All patients (100.0%) had prospective data collection to assess the prevalence of PE. D-dimer level was available for 18/20 (90.0%) patients and 3-month follow-up evaluation was performed in 16/20 (80.0%) patients. Challenges included the difficulty in recruiting patients since it is a population with many comorbidities, adequate c-PTP assessment using validated clinical decision rules, absence of consistent PE diagnostic strategy use since patients were mostly investigated according to the physician's impression and adequate 3-month follow-up since 25% of the patients had some protocol deviation for the follow-up. No PE was diagnosed during the entire study period. Conclusion: This pilot study shows the feasibility in prospectively collecting data to evaluate the prevalence of PE in patients admitted for AECOPD in Canada. Also, challenges were assessed and included recruitment of patients, adequate c-PTP assessment, consistent PE diagnostic strategy use and adequate 3-month follow-up.

Failure rate of D-dimer testing in patients with high clinical probability of pulmonary embolism: Ancillary analysis of three European studies.

In patients with a high clinical probability of pulmonary embolism (PE), the high prevalence can lower the D-dimer negative predictive value and increase the risk of diagnostic failure. It is therefore recommended that these high-risk patients should undergo chest imaging without D-dimer testing although no evidence supports this recommendation. The objective was to evaluate the safety of ruling out PE based on D-dimer testing among patients with a high clinical probability of PE. This was a post hoc analysis of three European studies (PROPER, MODIGLIANI, and TRYSPEED). Patients were included if they presented a high clinical probability of PE (according to either the Wells or the revised Geneva score) and underwent D-dimer testing. The D-dimer-based strategy ruled out PE if the D-dimer level was below the age-adjusted threshold (i.e., <500 ng/mL in patients aged less than 50 and age × 10 ng/mL in patients older than 50). The primary endpoint was a thromboembolic event in patients with negative D-dimer either at index visit or at 3-month follow-up. A Bayesian approach estimated the probability that the failure rate of the D-dimer-based strategy was below 2% given observed data. Among the 12,300 patients included in the PROPER, MODIGLIANI, and TRYSPEED studies, 651 patients (median age 68 years, 60% female) had D-dimer testing and a high clinical probability of PE and were included in the study. PE prevalence was 31.3%. Seventy patients had D-dimer levels under the age-adjusted threshold, and none of them had a PE after follow-up (failure rate 0.0% [95% CI 0.0%-6.5%]). Bayesian analysis reported a credible interval of 0.0%-4.1%, with a 76.2% posterior probability of a failure rate below 2%. In this study, ruling out PE in high-risk patients based on D-dimer below the age-adjusted threshold was safe, with no missed PE. However, the large CI of the primary endpoint precludes a definitive conclusion.

Optimizing resource allocation: Cost-effectiveness of specified D-dimer cut-offs in cancer patients with suspected venous thromboembolism

An accurate diagnosis of venous thromboembolism (VTE) is crucial, given the potential for high mortality in undetected cases. Strategic D-dimer testing may aid in identifying low-risk patients, preventing overdiagnosis and reducing imaging costs. We conducted a retrospective, comparative analysis to assess the potential cost savings that could be achieved by adopting different approaches to determine the most effective D-dimer cut-off value in cancer patients with suspected VTE, compared to the commonly used rule-out cut-off level of 0.5 mg/L. The study included 526 patients (median age 65, IQR 55–75) with a confirmed cancer diagnosis who underwent D-dimer testing. Among these patients, the VTE prevalence was 29% (n = 152). Each diagnostic strategy's sensitivity, specificity, negative likelihood ratio (NLR), as well as positive likelihood ratio (PLR), and the proportion of patients exhibiting a negative D-dimer test result, were calculated. The diagnostic strategy that demonstrated the best balance between specificity, sensitivity, NLR, and PLR, utilized an inverse age-specific cut-off level for D-dimer [0.5 + (66-age) × 0.01 mg/L]. This method yielded a PLR of 2.9 at a very low NLR for the exclusion of VTE. We observed a significant cost reduction of 4.6% and 1.0% for PE and DVT, respectively. The utilization of an age-adjusted cut-off [patient’s age × 0.01 mg/L] resulted in the highest cost savings, reaching 8.1% for PE and 3.4% for DVT. Using specified D-dimer cut-offs in the diagnosis of VTE could improve economics, considering the limited occurrence of confirmed cases among patients with suspected VTE.Graphical In the context of accurate diagnosis of VTE, strategic D-dimer testing helps identify low-risk patients, preventing overdiagnosis and reducing imaging costs. In our retrospective study, the diagnostic strategy that demonstrated the best balance between specificity, sensitivity, and best PLR, utilized an inverse age-specific cut-off level for D-dimer. We observed a significant cost reduction of 4.6% for PE and 1% for DVT. Abbreviations: CTPA, computed tomography pulmonary angiography; CUS, compression ultrasound; DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism.

Implementation, Clinical Benefit and Safety of a D-Dimer-Focused Pulmonary Embolism Testing Pathway in the Emergency Department

Computed tomography pulmonary angiogram (CTPA) is overused during pulmonary embolism (PE) testing in the emergency department (ED), whereas prediction rules and D-dimer are underused. We report the adherence, clinical benefit, and safety of a D-dimer-only strategy to guide need for PE imaging in the ED. This was a prospective multicenter implementation study in 2 EDs with historical and external controls. Patients with suspected PE underwent D-dimer testing and imaging (CTPA or ventilation-perfusion scan) when D-dimer levels were 500 ng/mL or more. PE was ruled out if D-dimer was less than 500 ng/mL or with negative imaging. The primary implementation outcome was the proportion of patients tested for PE in adherence with the pathway. The primary clinical benefit outcome was the proportion of patients tested for PE who received pulmonary imaging. The primary safety outcome was diagnosis of PE in the 30 days following negative PE testing postimplementation. Between January 2018 and June 2021, 16,155 patients were tested for PE, including 33.4% postimplementation, 30.7% preimplementation, and 35.9% in an external control site. Adherence with the D-dimer-only pathway was 97.6% (adjusted odds ratio (aOR) post- versus preimplementation 5.26 (95% confidence interval 1.70 to 16.26). There was no effect on the proportion undergoing PE imaging. Imaging yield increased aOR 4.89 (1.17 to 20.53). Two cases of PE (0.04%; 0.01% to 0.16%) were diagnosed within 30 days. In this Canadian ED study, the uptake of a D-dimer-only PE testing strategy was high. Implementation was associated with higher imaging yield and a D-dimer level of less than 500 ng/mL safely excluded PE.

Epidemiological, Clinical and Radiological Profile of Patients Hospitalized for COVID-19 at the Epidemic Treatment Centre of the Fann Hospital, Dakar during the Third and Fourth Waves

Aims: To describe the epidemiological, clinico-biological and radiological aspects of patients hospitalized for COVID-19 infection at the Fann Epidemics Treatment Center (ETC).&#x0D; Methodology: Cross-sectional study in Fann hospital, between July 2021 and March 2022. We included all patients hospitalized for COVID-19 infection on the basis of epidemiological, clinical and CT scanographic evidence associated with a positive RT-PCR or Ag RDT. The data were entered into Excel and analysed using R software. Qualitative variables were expressed as absolute and relative frequencies. Quantitative variables were described by the average accompanied by its standard deviation or the median associated with the extremes according to their distribution.&#x0D; Results: A total of 248 patients were enrolled during the study period. The average age was 61.7 ±15.2 years. Of the 248 patients, 110 were women (44.4%). High blood pressure was the most frequent comorbidity and was found in 89 patients (35.89%), followed by diabetes (21.7%) and obesity (7.26%) respectively. Three quarters (76.6%) of our patients had not been vaccinated against COVID-19. Dyspnoea was the most frequently encountered clinical symptoms (77%). More than a third of patients (39%) had extra-respiratory symptoms. A total of 109 patients underwent d-dimer testing, of whom 80 (73.4%) had levels ≥ 500ng/ml. One hundred and eighty-two patients (73.4%) had undergone thoracic CT or CT angio. And among them, 71.9% had ground-glass lesions, and half (50%) had severe to critical lesions. In our study, 52 patients died, representing a case-fatality rate of 21%.&#x0D; Conclusion: Our study population consisted mainly of elderly subjects, most of whom had not been vaccinated against COVID-19 and had one or more comorbidities, the most representative of which were high blood pressure, diabetes and heart diseases. In this population, the mortality rate of COVID-19 was significant, approximately one in four patients.

A study of modified Wells score for pulmonary embolism and age-adjusted D-dimer values in patients at risk for deep venous thrombosis.

Pulmonary embolism (PE) is the most severe complication of deep venous thrombosis (DVT). This study was designed to evaluate the usefulness of modified Wells score combined with age-adjusted D-dimer cut-off levels as a clinical pre-test probability assessment for predicting PE in patients 'at risk for DVT.' This was a cross-sectional study including 200 in-patients at risk for DVT. Patients were categorized as 'pulmonary embolism unlikely' or 'pulmonary embolism likely' using modified Wells score and underwent D-dimer testing. PE was considered excluded in patients classified as unlikely with normal D-dimer levels, whereas the rest of the patients underwent computed tomography pulmonary angiogram (CTPA). Out of 200 patients, 163 patients (81.50%) were 'pulmonary embolism unlikely,' whereas 37 patients (18.50%) were 'pulmonary embolism likely.' Of 163 patients categorized as 'pulmonary embolism unlikely,' 67 patients (41.5%) had normal D-dimer values and were excluded from CTPA. PE was detected in 24.2% of the patients who underwent CTPA. The combined strategy using modified Wells score and age-adjusted D-dimer cut-off value has 100% sensitivity and a negative predictive value and can be used to safely exclude PE in in-patients.

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study

AbstractD-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.

Thrombotic burden, D-dimer levels and complete compression ultrasound for diagnosis of acute symptomatic deep vein thrombosis of the lower limbs

BackgroundDiagnostic algorithms for deep vein thrombosis (DVT) include D-dimer for its high negative predictive value, thus reducing the need for imaging. Small thrombi may be associated with low D-dimer levels, increasing false negatives. AimTo assess the sensitivity and thus the false negative rates of standard and age-adjusted D-dimer cut offs for isolated distal DVT (IDDVT) in outpatients. Materials and methodsWe enrolled consecutive outpatients with suspected DVT of the lower limbs referring to our vascular emergency department from 2009 to 2018. Patients underwent D-dimer testing (STA, Stago, cut-off: 500 μg/L), pretest clinical probability (PTP) evaluation and complete compression ultrasonography. Follow-up was 3 months. ResultsAmong 3948 patients (M:1554–39%, median age 69), 486 proximal DVTs (12.3%) and 348 IDDVTs (8.8%) were diagnosed. Median D-dimer was higher in proximal than IDDVT (3960 vs 1400 μgr/L; p = 0.001). The false negative rate of the standard D-dimer cut-off was 2% (95%CI: 0.8–3.2%) for proximal DVT and 14.7% (95% CI: 11–81%) for IDDVT. The false negative rate of the age-adjusted cut-off was 4.9% (3–7%) for proximal DVT and 19.5% (95% CI: 15.4–24.7%) for IDDVT. Conclusions: Small calf thrombi are associated with low D-dimer levels, and age-adjusted D-dimer may be below the cut-off more frequently in subjects with IDDVT than standard cut-off D-dimer, although such D-dimer levels might exclude IDDVT that require treatment.

Medical Imaging Stewardship and Healthcare Savings: Utilization of Age Adjusted D-Dimer to Rule Out Acute Pulmonary Embolism.

Acute pulmonary embolism (PE) is a common diagnosis that can lead to death if left untreated. Computerized tomography pulmonary angiogram scan (CTPA) is the gold standard for diagnosis of PE. Utilization of CTPA is increasing in the emergency setting even when suspicion for PE is very low. While CTPA is helpful, radiation exposure, contrast reactions, and cost must be considered. D-dimer is a well-established, high sensitivity and low specificity laboratory test that can effectively rule out PE in low-risk patients when negative. The ADJUST-PE trial showed that there is a natural rise of D-dimer levels with age. This age adjusted D-dimer level is meant to prevent unnecessary CTPA exams in low suspicion patients. We hypothesize that there are a significant amount of unwarranted CTPA exams ordered at our community hospital that would not have been performed if the age adjusted D-dimer level were implemented. During a four-month period we collected a list of patients 18 years of age and older who received a CTPA exam for initial evaluation of possible acute PE at our institution. The primary outcome was to evaluate the percentage of patients who received an imaging study despite a negative D-dimer collected prior to the study, using the age adjusted upper limit of normal based on the ADJUST-PE study. There were 734 CTPA exams that met our criteria in a four-month period. D-dimer levels were checked in 30.38% (223 of 734) of cases prior to imaging. Out of these 223 cases, 21.08% (47 of 223) were found to have negative age adjusted D-Dimer levels yet still received an imaging study. Out of these 47 cases, 44% (21 of 47) would have been positive using the traditional D-dimer threshold. This study demonstrates that by adherence to the guideline-based pre-test algorithm and also utilizing the recommendations set forth by the ADJUST-PE study, approximately 21% of patients who undergo D-dimer testing would avoid unwarranted CT imaging. In addition to decreased radiation and contrast exposure, a significant amount of health care expense would be saved.

Elevation of the D-dimer cut-off level might be applicable to rule out pulmonary embolism for active cancer patients in the emergency department.

Recent guidelines for diagnosing acute pulmonary embolism (PE) are based on clinical decision rules and D-dimer. D-dimer measurement is recommended only for patients who are 'PE-unlikely'. We aimed to assess the current guidelines for cancer patients and to determine an optimal D-dimer cut-off level. This retrospective observational study was conducted in the emergency department of Asan Medical Center (Seoul, Korea) between 02/2017 and 09/2017 for the development cohort and between 06/2018 and 02/2019 for the validation cohort. Among adult active cancer patients with suspected PE, we included those who were 'PE-unlikely' according to Wells' criteria and who underwent D-dimer testing and computed tomographic pulmonary angiography (CTPA). A total of 498 patients (227 in the development cohort and 271 in the validation cohort) were included, and PE was diagnosed in 8.8% and 18.5% of patients, respectively. The optimal D-dimer cut-off level was 2.0μg/mL. This elevated cut-off level showed a much higher specificity of 21.3% (95% confidence interval [CI] 16.2-27.3%) and 21.7% (95% CI 16.8-7.6%) in the development and validation sets, respectively, compared with the specificity of 4.4% (95% CI 2.3-8.1%) and 4.1% (95% CI 2.2-7.6%) using the age-adjusted cut-off. The new D-dimer cut-off value identified unnecessary CTPA for 21.3% of patients (absolute difference, 16.9%, 35 of 207) in the development cohort and 21.7% (absolute difference, 17.6%, 39 of 221) of patients in the validation cohort compared to using the standard age-adjusted cut-off. The elevated D-dimer cut-off value combined with Wells' criteria might reduce unnecessary CTPA in active cancer patients with a 'PE-unlikely' classification. Further clinical trials are warranted to improve the PE diagnostic strategy in cancer patients.

P039: Utilization of serum D-dimer assays and computed tomography pulmonary angiography (CTPA) scans in the diagnosis of pulmonary embolism among emergency department (ED) physicians

Introduction: As the availability of Computed Tomography Pulmonary Angiography (CTPA) to rule out pulmonary embolism (PE) increases, so too does its utilization, and consequent overutilization. A variety of evidence-based algorithms and decision rules using clinical criteria and D-Dimer testing have been proposed as instruments to allow physicians to safely rule out a PE in low-risk patients. However, studies have shown mixed results with respect to both physician uptake of these decision rules and their impact on improving ordering practices among physicians. The objective of this study is to describe the prevalence of D-Dimer utilization among ED physicians and its impact on positive yield rates of CTPAs in a community setting. Methods: Data was collected on all CTPA studies ordered by ED physicians at two very high-volume community hospitals and an affiliated urgent care centre during the 2-year period between January 1, 2016 and December 31, 2017. For each CTPA, we determined if 1) a D-Dimer had been ordered prior to CTPA, if 2) the D-Dimer was positive, and if 3) the CTPA was positive for a PE. Using a chi-square test, we compared the diagnostic yield for those patients who had a D-Dimer prior to their CTPA and those who did not. Results: A total of 2,811 CTPAs were included in the analysis. Of these, 964 CTPAs (34.3%) were ordered without a D-Dimer. Of those 1,847 patients who underwent D-Dimer testing prior to the CTPA, 343 (18.7%) underwent a CTPA despite a negative D-Dimer. When compared as a group, those CTPAs preceded by a D-Dimer showed no significant difference in positive yields when compared to those CTPAs ordered without a prior D-Dimer (9.9% versus 11.3%, p = 0.26). Conclusion: The findings of this study present a complicated picture of the impact of D-Dimer utilization on CTPA ordering patterns. There is evidence of suboptimal uptake of routine D-Dimer ordering, and adherence to guidelines in terms of forgoing CTPAs in low-risk patients with negative D-Dimers. While this study design leaves unanswered the question of how many CTPAs were avoided as a result of a negative D-Dimer, the finding of a similar positive yield among those patients who had a D-Dimer ordered versus those who did not is interesting, and illustrative of the issues arising from the high false-positive rates associated with D-Dimer screening.

Retrospective review of D-dimer testing for venous thrombosis recurrence risk stratification: is this a useful test in the real world?

Predicting the risk of recurrence after venous thromboembolism (VTE) remains an important clinical challenge. Post-anticoagulation cessation D-dimer has previously been shown to be associated with increased VTE recurrence in unprovoked major VTE, however this is not routinely used clinically and has not been validated in provoked VTE and isolated distal DVT (IDDVT). We aimed to retrospectively evaluate this practice in the real-world setting including examining its use in provoked VTE and IDDVT. Consecutive patients diagnosed with DVT or PE between January 2013 and December 2016 were retrospectively evaluated. Clinical features, VTE risk factors, recurrence and bleeding rates were evaluated for patients with normal and abnormal post-anticoagulation D-dimer, as well as those patients who did not undergo D-dimer testing. Patients with active malignancy, superficial vein thrombosis and inadequate follow-up were excluded. Of the 1033 patients with a diagnosis of VTE in the study period, 173 were included in the "D-dimer tested" group, and 254 in the "D-dimer un-tested" comparison group. Abnormal post-anticoagulation D-dimer was significantly associated with VTE recurrence (HR 5.96, 95% CI 2.15-14.57, p < 0.001). Abnormal D-dimer was also associated with high risk of VTE recurrence in travel-provoked VTE (67.61 events per 100 patient-years), and unprovoked IDDVT (HR 14.37, 95% CI 1.75-117.83, p = 0.013). Males with abnormal post-anticoagulation D-dimer were associated with the highest risk of VTE recurrence (HR 12.95, 95% CI 2.78-60.20, p = 0.001). Patients with unprovoked proximal DVT and/or PE who underwent D-dimer testing had a lower VTE recurrence rate compared to those who did not have D-dimer testing (HR 0.28, 95% CI 0.10-0.80, p = 0.017). We confirm the utility of post-anticoagulation cessation D-dimer testing to stratify VTE recurrence risk in the real-world setting, including potentially a role of this assay for predicting subsequent VTE in travel-provoked VTE and unprovoked IDDVT.

Practical Utility of D-dimer Test for Venous Thromboembolism in Systemic Lupus Erythematosus Depends on Disease Activity: a Retrospective Cohort Study.

BackgroundThe D-dimer test is a screening tool for venous thromboembolism (VTE); however, its utility for patients with systemic lupus erythematosus (SLE) remains unclear. Here, we examined the utility of the D-dimer test as a screening tool for VTE in SLE patients.MethodsSLE patients (n = 276) and age- and sex-matched patients with non-rheumatic disease (n = 1,104), all of whom underwent D-dimer testing to screen for VTE, were enrolled. The sensitivity and specificity and receiver operating characteristics curve of the D-dimer test were compared in both groups. Then, subgroup of SLE patients in whom the D-dimer test can be useful was sought.ResultsThe incidence of VTE was more common in SLE patients than controls (10.9% vs. 4.0%). Although the sensitivity of the D-dimer test was comparable between SLE patients and controls (93.3% vs. 90.9%), the specificity of the test was profoundly lower in SLE patients compared to controls (28.4% vs. 84.4%). The area under the curve (AUC) of the D-dimer for VTE was 0.669 in SLE patients and 0.90 in control group. Multiple linear regression analysis demonstrated that SLE disease activity index-2000 (SLEDAI-2K) was significantly associated with D-dimer levels in SLE patients (β = 0.155; P = 0.022). Subgroup analysis showed that the AUC is moderate (0.768) with low disease activity, while it is low (0.518) with high SLEDAI-2K.ConclusionThe D-dimer test may not be a useful screening tool for VTE in patients with active SLE. D-dimer test for predicting VTE in SLE patients should be differentially applied according to disease activity of SLE.

Can an age-adjusted D-dimer level be adopted in managing venous thromboembolism in the emergency department? A retrospective cohort study.

Patients suspected of having venous thromboembolism (VTE), with a low pretest probability, undergo D-dimer testing. A negative D-dimer, in a low-risk patient rules out VTE with a high degree of certainty because of its high sensitivity. It is, however, a poorly specific test, and the absolute value increases with age. The aim of this study was to establish whether an age-adjusted D-dimer could be safely used instead of a standard cut-off level in low-risk patients over the age of 50 years. This was a retrospective review of 1649 patients with suspected VTE whose D-dimer levels were analysed. In low-risk patients (defined as 'VTE unlikely' using the dichotomized Wells' scores), the outcomes in terms of confirmed VTE diagnosis, hospital admission and investigations using an age-adjusted D-dimer level (measured in D-dimer units) of 5× the age for patients over 50 years of age and 250 ng/ml for patients younger than 50 years of age, was compared with the cut-off standard level (230 ng/ml in all patients). Of the total group of patients in the VTE unlikely group, the proportion of patients with a negative D-dimer when using the standard cut-off was 64.9% (859/1324). A further 130 patients had a negative D-dimer when the age-adjusted cut-off was used, increasing the proportion of all patients in whom VTE could be excluded without imaging to 74.7% (989/1324).For those patients of 75 years or older, the proportion of patients in whom VTE could be excluded without imaging increased from only 91/242 (37.6%) when using the standard D-dimer cut-off to 154/242 (63.6%) when the age-adjusted cut-off was used.These changes occurred without any additional false-negative findings. For patients over the age of 50 years suspected of having VTE with a low pretest probability, increasing the D-dimer cut-off level to 5× the age increases the proportion of patients in whom VTE can safely be excluded without radiological imaging.

Age-adjusted D-dimer thresholds in the investigation of suspected pulmonary embolism: A retrospective evaluation in patients ages 50 and older using administrative data.

D-dimer testing is an important component of the workup for pulmonary embolism (PE). However, age-related increases in D-dimer concentrations result in false positives in older adults, leading to potentially unnecessary imaging utilization. The objective of this study was to quantify the test characteristics of an age-adjusted D-dimer cut-off for ruling out PE in older patients investigated in actual clinical practice. This observational study used administrative data from four emergency departments from July 2013 to January 2015. Eligible patients were ages 50 and older with symptoms of PE who underwent D-dimer testing. The primary outcome was 30-day diagnosis of PE, confirmed by imaging reports. Test characteristics of the D-dimer assay were calculated using the standard reference value (500 ng/ml), the local reference value (470 ng/ml), and an age-adjusted threshold (10 ng/ml × patient’s age). This cohort includes 6,655 patients ages 50 and older undergoing D-dimer testing for a possible PE. Of these, 246 (3.7%) were diagnosed with PE. Age-adjusted D-dimer cut-offs were more specific than standard cut-offs (75.4% v. 63.8%) but less sensitive (90.3% v. 97.2%). The false-negative risk in this population was 0.49% using age-adjusted D-dimer cut-offs compared with 0.15% with traditional cut-offs. Age-adjusted D-dimer cut-offs are substantially more specific than traditional cut-offs and may reduce CT utilization among older patients with suspected PE. We observed a loss of sensitivity, with an increased risk of false-negatives, using age-adjusted cut-offs. We encourage further evaluation of the safety and accuracy of age-adjusted D-dimer cut-offs in actual clinical practice.

Retrospective validation of the pulmonary embolism rule-out criteria rule in 'PE unlikely' patients with suspected pulmonary embolism.

Patients presenting to emergency departments (EDs) with suspected pulmonary embolism (PE) can be risk stratified and those who are deemed to be at low risk for PE usually undergo D-dimer testing. A negative D-dimer in this low-risk group rules out PE with a high degree of certainty because of its high sensitivity. The D-dimer is, however, a poorly specific test and positive results often lead to unnecessary radiological imaging (notably computed tomography pulmonary angiography). The Pulmonary Embolism Rule-Out Criteria (PERC) rule has been suggested as an alternative to D-dimer testing in these patients. This study looked at whether the PERC rule could safely replace the use of D-dimer in patients suspected of PE, but deemed 'PE unlikely' by the dichotomized Wells score in a UK ED setting. This was a retrospective review of 986 patients with suspected PE who had a blood sample for D-dimer level taken. In patients deemed 'PE unlikely' (using the dichotomized Wells score), the diagnostic performance of the PERC rule was compared with a standard D-dimer level in the detection of PE at index presentation and up to 3 months afterwards. Of the 986 patients, 940 patients were deemed 'PE unlikely' using the dichotomized Wells score. Three patients with confirmed PE would have been missed by the PERC rule compared with only one missed by the D-dimer test. In these patients, the sensitivity of the PERC rule for detecting PE was 91.4% [95% confidence interval (CI): 76.9-98.2%], with a negative likelihood ratio of 0.25 (95% CI: 0.08-0.73). However, the negative predictive value of the PERC rule was 99.1% (95% CI: 97.3-99.8%). In comparison, the sensitivity for the standard D-dimer test was 97.1% (95% CI: 85.1-99.9%), with a negative likelihood ratio of 0.04 (95% CI: 0.01-0.27). The negative predictive value for the standard D-dimer test was 99.8% (95% CI: 99.2-100%). The PERC rule has a high negative predictive value for excluding PE in patients presenting with suspected PE to the ED. However, the PERC rule may still miss around 8% of confirmed PE in patients who are deemed 'PE unlikely' by a dichotomized Wells score. Caution is advised in using the PERC rule as a substitute for the standard D-dimer test in all these patients.

Screening of Deep Vein Thrombosis Prior to Surgery Using D-dimer Testing and Venous Ultrasonography of Lower Extremities

Deep vein thrombus (DVT) in a patient awaiting surgery is a considerable source of pulmonary embolisms (PEs) during the surgical period, but screening for DVTs has not been emphasized. This retrospective study was conducted to identify factors associated with a positive D-dimer result and DVT diagnosis in order to evaluate the usefulness of DVT screening for patients awaiting surgery. A total of 1,061 patients (872 males, 189 females) underwent D-dimer testing prior to urological surgery at Tsukuba University Hospital between April 2013 and March 2016. Factors associated with a positive D-dimer result and DVT diagnosis were determined by a univariate analysis. Among the 75 patients with a positive Ddimer result, venousultras onography of the lower extremitieswasperformed in 69 patientsand DVT was diagnosed in 14 patients. The overall true-positive rate of D-dimer was 20. 3% (14/69), and it was significantly higher in the females (males11.3% vsfemales50% ; p＝0.0021). Age, body mass index and Ddimer value were not associated with the true-positive D-dimer result. Among the 1,061 patients, DVT was significantly more likely to be diagnosed in elderly patients (median age 73.5 vs 67 yrs, p＝0.0087) and females(males0. 69% vsfemales4. 23% ; p＝0. 0010). Among the three patientswith an acute-phase thrombus, two postponed surgery and required anti-thrombus therapy, and the other patient underwent the implantation of an inferior vena cava filter in order to undergo surgery on schedule. No PE occurred during the surgical period. These results indicate that DVT screening for patients awaiting surgery is useful and should be considered as part of the prevention of PEs during the surgical period.

Validation of STA-Liatest D-Di assay for exclusion of pulmonary embolism according to the latest Clinical and Laboratory Standard Institute/Food and Drug Administration guideline. Results of a multicenter management study

Combined clinical pretest probability (PTP) and D-dimer testing have great diagnostic value for pulmonary embolism exclusion. To harmonize performance levels of D-dimer assays available on the market, the Clinical and Laboratory Standard Institute (CLSI) has published a guideline, endorsed by the US Food and Drug Administration (FDA). Such guideline specifies the ideal D-dimer assay characteristic and target population. This study was conducted following the CLSI guideline to upgrade the assay-intended use and obtain FDA clearance of STA-Liatest D-Di assay for pulmonary embolism exclusion in patient with low/moderate PTP. This was an international, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard of care setting. D-dimer assay was performed in consecutive, ambulatory outpatients suspected of pulmonary embolism, with low/moderate PTP, and without medical conditions or in clinical settings known to alter default D-dimer values regardless of the presence of thrombosis using a threshold of 0.5 μg/ml (fibrinogen equivalent units) for venous thromboembolism exclusion. Results were used to determine test performance. Of 1141 patients who underwent D-dimer testing, 1060 had valid results and completed study as planned. STA-Liatest D-Di assay performance has exceeded the CLSI/FDA guidance requirements, with a sensitivity of 97.6% (95% confidence interval: 91.7–99.7%) and a negative predictive value of 99.7% (95% confidence interval: 99.0–100%). STA-Liatest D-Di assay has an excellent performance when used in combination with a PTP score in relevant patients and has the potential to minimize the economic healthcare burden avoiding unnecessary and expensive imaging tests.

Yield of CT Pulmonary Angiography in the Emergency Department When Providers Override Evidence-based Clinical Decision Support

Purpose To determine the frequency of, and yield after, provider overrides of evidence-based clinical decision support (CDS) for ordering computed tomographic (CT) pulmonary angiography in the emergency department (ED). Materials and Methods This HIPAA-compliant, institutional review board-approved study was performed at a tertiary care, academic medical center ED with approximately 60 000 annual visits and included all patients who were suspected of having pulmonary embolism (PE) and who underwent CT pulmonary angiography between January 1, 2011, and August 31, 2013. The requirement to obtain informed consent was waived. Each CT order for pulmonary angiography was exposed to CDS on the basis of the Wells criteria. For patients with a Wells score of 4 or less, CDS alerts suggested d-dimer testing because acute PE is highly unlikely in these patients if d-dimer levels are normal. The yield of CT pulmonary angiography (number of positive PE diagnoses/total number of CT pulmonary angiographic examinations) was compared in patients in whom providers overrode CDS alerts (by performing CT pulmonary angiography in patients with a Wells score ≤4 and a normal d-dimer level or no d-dimer testing) (override group) and those in whom providers followed Wells criteria (CT pulmonary angiography only in patients with Wells score >4 or ≤4 with elevated d-dimer level) (adherent group). A validated natural language processing tool identified positive PE diagnoses, with subsegmental and/or indeterminate diagnoses removed by means of chart review. Statistical analysis was performed with the χ2 test, the Student t test, and logistic regression. Results Among 2993 CT pulmonary angiography studies in 2655 patients, 563 examinations had a Wells score of 4 or less but did not undergo d-dimer testing and 26 had a Wells score of 4 or less and had normal d-dimer levels. The yield of CT pulmonary angiography was 4.2% in the override group (25 of 589 studies, none with a normal d-dimer level) and 11.2% in the adherent group (270 of 2404 studies) (P < .001). After adjustment for the risk factor differences between the two groups, the odds of an acute PE finding were 51.3% lower when providers overrode alerts than when they followed CDS guidelines. Comparison of the two groups including only patients unlikely to have PE led to similar results. Conclusion The odds of an acute PE finding in the ED when providers adhered to evidence presented in CDS were nearly double those seen when providers overrode CDS alerts. Most overrides were due to the lack of d-dimer testing in patients unlikely to have PE. © RSNA, 2016.

Ruling out low- and moderate-risk probability pulmonary emboli without radiological imaging: appraisal of a clinical prediction algorithm after implementation and revision with higher D-dimer thresholds.

A study conducted at an Australian hospital between 2007 and 2009 led to the implementation of a clinical prediction algorithm for pulmonary embolism (PE) consisting of the Wells criteria and D-dimer testing. Since then, studies conducted in other countries have recommended new D-dimer cut-offs to the algorithm. To appraise the implemented algorithm and see if its ability to stratify patient risk has been maintained and to test retrospectively new D-dimer thresholds. Data from 300 patients with computed tomography pulmonary angiograms (CTPA) scans between February 2010 and March 2012 were included. Results were reviewed for algorithm compliance, patient risk stratification and PE prevalence. A higher D-dimer and an age-adjusted D-dimer cut-off were then retrospectively applied to the algorithm and results were re-evaluated. Pre-test probabilities between the current and original study remain within 1%, with slightly higher PE prevalence in the original study (12.7% vs 13.8%). Of the imaged cases, 14% (42/300) were not compliant with the algorithm. Of the low- and moderate-risk patients that underwent D-dimer testing, the retrospective application of 0.5 mg/L D-dimer cut-off resulted in a further 12.1% (95% confidence intervals 8.0-17.1%) of patients excluded from undergoing a CTPA. When combined with an age-adjusted D-dimer cut-off, 27.9% (60/215 95% confidence intervals 22.0-34.3%) were excluded from undergoing a CTPA. The implemented algorithm has maintained risk stratification and PE prevalence results. Along with evidence in other studies, we have shown that raising the D-dimer and applying age-adjusted D-dimer cut-offs might improve the efficiency of the clinical prediction algorithm in patients aged over 50.