Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients

Stals, Milou A.M.; Kaptein, Fleur H.J.; Kroft, Lucia J.M.; Klok, Frederikus A.; Huisman, Menno V.

doi:10.1080/00325481.2021.1920723

Cited by 17 publications

(19 citation statements)

References 76 publications

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“…However, in COVID-19 patients, markedly elevated D-dimers were reported to indicate patients with a high probability of VTE and, therefore, increased D-dimer levels, which may be proposed to initiate the diagnostic workup for VTE [ 2 ]. There is an ongoing discussion on the optimal cut-off value that should mandate VTE diagnostic assessment, with some authors suggesting values previously applied for PE and non-adjusted higher than conventional thresholds, such as 1000 ng/mL [ 6 ]. Since the most commonly used conventional non-age-adjusted threshold for D-dimer levels (i.e., upper limit of normal 500 ng/mL) is not adequate in this patient population, and the notion of employing D-dimer testing in PE diagnostic assessment in COVID-19 patients has even been discouraged [ 12 ], we examined other, non-standard thresholds—namely, the cut-offs calculated from the formula: D-dimer level/patient’s age, with the threshold > 70.…”

Section: Discussionmentioning

confidence: 99%

“…The standard PE diagnostic protocol includes D-dimer concentration testing and imaging studies [ 4 ]. PE, in the setting of acute viral pneumonia, has not been studied before, and, therefore, the standard thresholds for diagnostic markers cannot be extrapolated onto the COVID-19 population [ 3 , 5 , 6 ]. There is an on-going discussion on the optimal D-dimer cut-off levels for PE diagnosis in COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

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Age-Adjusted D-Dimer Levels May Improve Diagnostic Assessment for Pulmonary Embolism in COVID-19 Patients

Machowski

Polańska

Gałecka-Nowak

et al. 2022

JCM

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Introduction: SARS-CoV-2 infection leads to a hypercoagulable state. The prevalence of pulmonary embolism (PE) seems to be higher in this subgroup of patients. Patients and methods: We combined data from two tertiary referral centers specialized in the management of PE. The aims of this study were as follows: (1) to evaluate the prevalence of PE among a large population of consecutive patients admitted for COVID-19 pneumonia in two centers, (2) to identify a plasma D-dimer threshold that may be useful in PE diagnostic assessment, (3) to characterize the abnormalities associated with PE and mortality in COVID-19 patients. Results: The incidence of symptomatic acute PE was 19.3%. For diagnosing PE in COVID-19 patients, based on ROC curve analysis, we identified a D-dimer concentration/patient’s age ratio of 70, which improved D-dimer diagnostic capacity for PE and led to a reclassification improvement of 14% (NRI 0.14, p = 0.03) when compared to a cut-off level of 1000 ng/mL. Especially in severe COVID-19 lung involvement, D-dimer/age ratio cut-off equal to 70 was characterized by high diagnostic feasibility (sensitivity, specificity, negative predictive value, positive predictive value of 83%, 94%, 96%, and 73%, respectively). Apart from PE status, lung involvement and troponin T concentration were also independent predictors of in-hospital mortality. In the subgroup of PE patients, mortality was comparable with non-PE patients (19/88 (21.5%) vs. 101/368 (27.4%) for non-PE, p = 0.26) and was associated with older age, higher Bova scores, and higher troponin T concentrations. Age was the sole independent predictor for mortality in this subgroup. Conclusions: PE in COVID-19 patients is common, but it may not influence mortality when managed at a specialized center. In suspected PE, age-adjusted D-dimer levels (upper limit of normal obtained from the formula patient’s age × 70) may still be a useful tool to start the diagnostic workup. In COVID-19 patients without PE, older age, more extensive parenchymal involvement, or higher D-dimer levels are factors predicting mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age-Adjusted D-Dimer Levels May Improve Diagnostic Assessment for Pulmonary Embolism in COVID-19 Patients

Machowski

Polańska

Gałecka-Nowak

et al. 2022

JCM

View full text Add to dashboard Cite

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“…A normal CT could still be repeated though to monitor the degree of pulmonary involvement or detect a possible superinfection. As commonly used clinical decision rules (i.e., WELLS, GENEVA or YEARS-criteria) are not validated in the ICU nor in the COVID-19 setting [ [28] , [29] , [30] , [31] ], the decision to perform a CTPA was made by the treating ICU-consultant in consultation with a daily multidisciplinary team consisting of a consultant microbiologist, a consultant pulmonologist and at least three other ICU consultants. Please see the Supplemental Material for the full diagnostic and treatment protocol on our ICU.…”

Section: Methodsmentioning

confidence: 99%

Multi-organ point-of-care ultrasound for detection of pulmonary embolism in critically ill COVID-19 patients – A diagnostic accuracy study

Lieveld

Heldeweg

Smit

et al. 2022

Journal of Critical Care

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Purpose Critically ill COVID-19 patients have an increased risk of developing pulmonary embolism (PE). Diagnosis of PE by point-of-care ultrasound (POCUS) might reduce the need for computed tomography pulmonary angiography (CTPA), while decreasing time-to-diagnosis. Materials & methods This prospective, observational study included adult ICU patients with COVID-19. Multi-organ (lungs, deep vein, cardiac) POCUS was performed within 24 h of CTPA, looking for subpleural consolidations, deep venous thrombosis (DVT), and right ventricular strain (RVS). We reported the scan time, and calculated diagnostic accuracy measures for these signs separately and in combination. Results 70 consecutive patients were included. 23 patients (32.8%) had a PE. Median scan time was 14 min (IQR 11–17). Subpleural consolidations' diagnostic accuracy was: 42.9% (95%CI [34.1–52.0]). DVT's and RVS' diagnostic accuracy was: 75.6% (95%CI [67.1–82.9]) and 74.4% (95%CI [65.8–81.8]). Their sensitivity was: 24.0% (95%CI [9.4–45.1]), and 40.0% (95%CI [21.3–61.3]), while their specificity was: 88.8% (95%CI [80.8–94.3]), and: 83.0% (95%CI [74.2–89.8]), respectively. Multi-organ POCUS sensitivity was: 87.5% (95%CI [67.6–97.3]), and specificity was: 25% (95%CI [16.9–34.7]). Conclusions Multi-organ rather than single-organ POCUS can be of aid in ruling out PE in critically ill COVID-19 and help select patients for CTPA. In addition, finding RVS can make PE more likely, while a DVT would preclude the need for a CTPA. Registration: www.trialregister.nl : NL8540.

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“…Prevalence of pulmonary embolism (PE) in patients with coronavirus disease 2019 (COVID-19) is high, and PE diagnosis is challenging in this specific population. [1][2][3][4][5][6][7][8] COVID-19-associated coagulopathy was described early on, as well as unusually high D-dimer levels in a large majority of patients. [9][10][11] The D-dimer level seems to be proportional to the extent of lung damage, and was also identified as an independent risk factor of in-hospital mortality.…”

Section: Introductionmentioning

confidence: 99%

Adjusting D-dimer to Lung Disease Extent to Exclude Pulmonary Embolism in COVID-19 Patients (Co-LEAD)

et al. 2022

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Introduction: D-dimer measurement is a safe tool to exclude pulmonary embolism (PE) but its specificity decreases in COVID-19. Our aim was to derive a new algorithm with specific D-dimer threshold in COVID-19 patients. Methods: We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to computed tomography (CT) extent of lung damage was derived in a patient set (n=337), and its safety assessed in an independent validation set (n=337). Results: According to ROC curves, in the derivation set D-dimer safely excluded PE, with one false negative when using a 900 ng/mL threshold when lung damage extent was <50% and 1700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm sensitivity was 98.2% (95% CI: 94.7–100.0) and its specificity 28.4% (95% CI: 24.1–32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI: 0.01–0.44) and the area under the curve (AUC) was 0.63 (95% CI: 0.60–0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI: 88.7–99.6) and 39.2% (95% CI: 32.2–46.1), respectively. The NLR was 0.08 (95% CI; 0.02–0.33) and the AUC did not differed from that of the derivation set (0.68 ,95% CI: 0.64–0.72, P = 0.097). Using the Co-LEAD algorithm, 76/250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA). Conclusion: The Co-LEAD algorithm safely excludes PE, and allows reducing the use of CTPA among COVID-19 patients. Further prospective studies are necessary to validate this strategy.

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Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients

Cited by 17 publications

References 76 publications

Age-Adjusted D-Dimer Levels May Improve Diagnostic Assessment for Pulmonary Embolism in COVID-19 Patients

Age-Adjusted D-Dimer Levels May Improve Diagnostic Assessment for Pulmonary Embolism in COVID-19 Patients

Multi-organ point-of-care ultrasound for detection of pulmonary embolism in critically ill COVID-19 patients – A diagnostic accuracy study

Adjusting D-dimer to Lung Disease Extent to Exclude Pulmonary Embolism in COVID-19 Patients (Co-LEAD)

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