Ruling out Pulmonary Embolism in Patients with (Suspected) COVID-19—A Prospective Cohort Study

Background Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients. Methods Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded. Informed consent was obtained by opt-out approach. Patients were managed by validated diagnostic strategies for suspected PE. We evaluated the safety (3-month failure rate) and efficiency (number of computed tomography pulmonary angiographies [CTPAs] avoided) of the applied strategies. Results Overall PE prevalence was 28%. YEARS was applied in 36%, Wells rule in 4.2%, and “CTPA only” in 52%; 7.4% was not tested because of hemodynamic or respiratory instability. Within YEARS, PE was considered excluded without CTPA in 29%, of which one patient developed nonfatal PE during follow-up (failure rate 1.4%, 95% CI 0.04–7.8). One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal venous thromboembolism (VTE) during follow-up (failure rate 8.8%, 95% CI 4.3–16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6–7.0). Conclusion Our results underline the applicability of YEARS in (suspected) COVID-19 patients with suspected PE. CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. The failure rate after a negative CTPA, used as a sole test or within YEARS, was non-negligible and reflects the high thrombotic risk in these patients, warranting ongoing vigilance.

LO55: Comparison of the age-adjusted D-dimer, clinical probability-adjusted D-dimer, and Wells rule with D-dimer for diagnosing deep vein thrombosis in the emergency department.

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.

LO81: Optimizing the use of CT scanning for pulmonary embolism in the emergency department

Introduction: Diagnosing pulmonary embolism (PE) can be challenging because the signs and symptoms are often non-specific. Studies have shown that evidence-based diagnostic algorithms are not always adhered to in the Emergency Department (ED), which leads to unnecessary CT scanning. In 2013, the American College of Chest Physicians identified CT pulmonary angiography as one of the top five avoidable tests. One solution is to use a clinical prediction rule combined with the D-dimer, which safely reduces the use of CT scanning. The objective of this study was to compare the proportion of patients tested for PE in two emergency departments, who 1) had a CT-PE and 2) whose diagnosis of PE was missed. We compared these rates to those if the Wells rule and D-dimer had been applied as standard. 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-PE, 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 rate of CT/VQ imaging and the false-negative rates were calculated. The false-negative rate was calculated as the number of patients diagnosed with PE within 30 days as a proportion of those patients who did not have a CT/VQ scan at initial presentation. Results: There were 1,189 patients included in this study. 55/1,189 patients (4.6%; 95%CI 3.6-6.0%) were ultimately diagnosed with PE within 30 days. 397/1,189 patients (33.4%; 95%CI 30.8-36.1%) had CT/VQ scans for PE. 3 out of 792 who were not scanned had a missed PE resulting in a false-negative rate of 0.4% (95% CI 0.1-1.1%). 80 patients had an elevated D-dimer or high Wells score but were not imaged. Furthermore, 75 patients who did not have an elevated D-dimer nor a high Wells score were imaged. Had Wells rule/D-dimer been adhered to, 402/1,189 patients (33.8%; 95%CI 31.9-36.6%) would have undergone imaging and the false negative rate would be 0/727, 0% (95%CI 0.0-0.5%). Conclusion: If the Wells rule and D-dimer was used in all patients tested for PE, a similar proportion would have a CT scan but fewer PEs would be missed.

Is a normal computed tomography pulmonary angiography safe to rule out acute pulmonary embolism in patients with a likely clinical probability?

SummaryA normal computed tomography pulmonary angiography (CTPA) remains a controversial criterion for ruling out acute pulmonary embolism (PE) in patients with a likely clinical probability. We set out to determine the risk of VTE and fatal PE after a normal CTPA in this patient category and compare these risk to those after a normal pulmonary angiogram of 1.7% (95%CI 1.0–2.7%) and 0.3% (95%CI 0.02–0.7%). A patient-level meta-analysis from 4 prospective diagnostic management studies that sequentially applied the Wells rule, D-dimer tests and CTPA to consecutive patients with clinically suspected acute PE. The primary outcome was the 3-month VTE incidence after a normal CTPA. A total of 6,148 patients were included with an overall PE prevalence of 24%. The 3-month VTE incidence in all 4,421 patients in whom PE was excluded at baseline was 1.2% (95%CI 0.48–2.6) and the risk of fatal PE was 0.11% (95%CI 0.02–0.70). In patients with a likely clinical probability the 3-month incidences of VTE and fatal PE were 2.0% (95%CI 1.0–4.1%) and 0.48% (95%CI 0.20–1.1%) after a normal CTPA. The 3-month incidence of VTE was 6.3% (95%CI 3.0–12) in patients with a Wells rule >6 points. In conclusion, this study suggests that a normal CTPA may be considered as a valid diagnostic criterion to rule out PE in the majority of patients with a likely clinical probability, although the risk of VTE is higher in subgroups such as patients with a Wells rule >6 points for which a closer follow-up should be considered.Supplementary Material to this article is available online at www.thrombosis-online.com.

Clinical Decision Rules for Pulmonary Embolism in Hospitalized Patients: A Systematic Literature Review and Meta-analysis

Background Clinical decision rules (CDRs) for pulmonary embolism (PE) have been validated in outpatients, but their performance in hospitalized patients is not well characterized. Objectives The goal of this systematic literature review was to assess the performance of CDRs for PE in hospitalized patients. Methods We performed a structured literature search using Medline, EMBASE and the Cochrane library for articles published on or before January 18, 2017. Two authors reviewed all titles, abstracts and full texts. We selected prospective studies of symptomatic hospitalized patients in which a CDR was used to estimate the likelihood of PE. The diagnosis of PE had to be confirmed using an accepted reference standard. Data on hospitalized patients were solicited from authors of studies in mixed populations of outpatients and hospitalized patients. Study characteristics, PE prevalence and CDR performance were extracted. The methodological quality of the studies was assessed using the QUADAS instrument. Results Twelve studies encompassing 3,942 hospitalized patients were included. Studies varied in methodology (randomized controlled trials and observational studies) and reference standards used. The pooled sensitivity of the modified Wells rule (cut-off ≤ 4) in hospitalized patients was 72.1% (95% confidence interval [CI], 63.7–79.2) and the pooled specificity was 62.2% (95% CI, 52.6–70.9). The modified Wells rule (cut-off ≤ 4) plus D-dimer testing had a pooled sensitivity 99.7% (95% CI, 96.7–100) and pooled specificity 10.8% (95% CI, 6.7–16.9). The efficiency (proportion of patients stratified into the ‘PE unlikely’ group) was 8.4% (95% CI, 4.1–16.5), and the failure rate (proportion of low likelihood patients who were diagnosed with PE during follow-up) was 0.1% (95% CI, 0–5.3). Conclusion In symptomatic hospitalized patients, use of the Wells rule plus D-dimer to rule out PE is safe, but allows very few patients to forgo imaging.

The Performance of the Original and Simplified Wells Scores in Combination with Age-Adjusted D-Dimer Testing in the Diagnostic Management of Pulmonary Embolism

Background: Among patients with suspected pulmonary embolism (PE), imaging can be safely withheld in those with a 'PE unlikely' Wells score and a negative D-dimer. A simplification of the Wells score has been proposed to improve clinical applicability (Table 1), but its performance is less clear, in particular in combination with age-adjusted D-dimer testing. Objectives: To compare the performance of the original and simplified Wells scores alone and in combination with age-adjusted D-dimer testing. Methods: Individual patient data from 7,268 patients with clinically suspected PE enrolled in 6 prospective diagnostic management studies were used. The discriminatory performance, calibration, and diagnostic accuracy of the original and simplified Wells scores were evaluated. The efficiency and failure rate of both dichotomized scores combined with age-adjusted D-dimer testing were compared using a one-stage random effects meta-analysis. Efficiency was defined as the proportion of patients in whom PE could be considered excluded based on a 'PE unlikely' Wells score and a D-dimer below the age-adjusted treshold, defined as ≤500 µg/L in patients of 50 years or younger and the patient's age times 10 µg/L in those older than 50 years. The failure rate was defined as the proportion of patients subsequently diagnosed with symptomatic venous thromboembolism during 3-month follow-up. Results: The discriminatory performance of the original and simplified Wells scores was comparable (c-statistic 0.73 [95% CI 0.72-0.75] vs. 0.72 [95% CI 0.70-0.73]). When combined with age-adjusted D-dimer testing, the original and simplified Wells rules had comparable efficiency (33% [95% CI 25-42%] vs 30% [95% CI 21-40%]) and failure rates (0.9% [95% CI 0.6-1.5%] vs. 0.8% [95% CI 0.5-1.3%]). Conclusion: Among patients with suspected PE, the original and simplified Wells rules in combination with age-adjusted D-dimer testing have similar performance in ruling out the disease. Given its ease of use in clinical practice, the simplified Wells rule may be preferred. Disclosures Huisman: Boehringer Ingelheim Pharma GmbH & Co.KG: Other: Grant support; GlaxoSmithKline: Other: Grant support; Bayer HealthCare: Other: Grant support; Pfizer: Other: Grant support; Actelion: Other: Grant support.