key: cord-1012348-67i01ruf
authors: Luu, Inge H.Y.; Kroon, Féline P.B.; Buijs, Jacqueline; Krdzalic, Jasenko; de Kruif, Martijn D.; Leers, Math P.G.; Mostard, Guy J.M.; Martens, Remy J.H.; Mostard, Remy L.M.; van Twist, Daan J.L.
title: Systematic screening for pulmonary embolism using the years algorithm in patients with suspected COVID-19 in the emergency department
date: 2021-09-24
journal: Thromb Res
DOI: 10.1016/j.thromres.2021.09.010
sha: 31d3cd688e3df3c387905f84c85a1b732373df2d
doc_id: 1012348
cord_uid: 67i01ruf

nan

Pulmonary embolism (PE) is a prevalent and potentially life-threatening complication of COVID-19. 1 To prevent further respiratory deterioration, early detection of concomitant PE is required, preferably upon hospital admission. In this study, we evaluated the diagnostic yield of systematic screening for PE in the Emergency Department (ED) in a consecutive cohort of patients with suspected COVID-19 who were admitted for hospital care.

We included all patients who were admitted to a large teaching hospital in the Netherlands via the ED between April 7th and May 31st 2020 and who met the WHO case definition for suspected COVID-19. 2 All patients were evaluated according to a prespecified clinical protocol, including systematic history taking, laboratory testing, computed tomography (CT) of the chest, and SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR).

In the ED, all patients were screened for PE according to the YEARS-algorithm. 3 This algorithm consists of three clinical items (clinical signs of deep vein thrombosis, hemoptysis, and PE as the most likely diagnosis) with simultaneous D-dimer testing (using CS2500 blood coagulation analysers, Sysmex Corporation, Kobe, Japan). Contrast-enhanced CT-pulmonary angiography (CTPA) was performed in patients with 0 YEARS-items and D-dimer ≥1000 ng/mL, and in patients with ≥1 YEARSitems and D-dimer ≥500 ng/mL. Patients who had D-dimer values below these cut-off values were considered to have PE excluded and underwent a non-contrast-enhanced chest-CT as part of the clinical protocol. Patients were excluded if they were already receiving a therapeutic dose of anticoagulant drugs for another indication, or in case of contraindication to CTPA (e.g., allergy to iodinated contrast agents, impaired renal function, or inability to cooperate) or to anticoagulant treatment because of active major bleeding.

Systematic PE-screening using the YEARS-algorithm was performed in all patients who met the WHO case definition for suspected COVID-19. 2 Yet, a definite diagnosis of COVID-19 (defined as either a positive SARS-CoV-2 RT-PCR or a COVID-19 CT-classification score (CO-RADS) 4 In the first study that systematically screened for PE in ED patients with (suspected) COVID-19, we found an overall PE-prevalence of 7.7%. Except for D-dimer, no other risk factors for PE were identified. One out of 7.7 CTPAs that were indicated according to the YEARS-algorithm were positive for PE. Therefore, we believe that this is a feasible approach for early PE-detection in these patients. However, despite this potential bias, the present study used a validated algorithm 3 and provides a much more reliable estimation of the true PE-prevalence, than previous studies that lacked systematic screening and were thus highly susceptible to inclusion and selection bias. 5 Since inflammation induces an increase in D-dimer levels, questions have been raised about the efficacy of the currently used D-dimer threshold in COVID-19 patients. Several studies have advocated the use of a higher D-dimer cut-off (between 2500 and 2900 μg/L) based on the highest "Youden's index" for an optimal cut-off point. 6, 7 However, these higher D-dimer thresholds yield a sensitivity of 80-83%, implying a substantial proportion (17-20%) of PEs will remain undiagnosed. In our cohort, adjusting the D-dimer threshold from 1000 to 2500 μg/L would have resulted in missing approximately 20% of the PEs (Figure 1 ). Hence, we believe that it is well justified to opt for a threshold with a sensitivity and a negative predictive value close to 100%. In our data, the lowest Ddimer value among patients with PE who met zero YEARS-items was 1258 μg/L, which is close to the threshold of 1000 μg/L used in the YEARS-algorithm. Accordingly, we do not advocate raising the Ddimer threshold in ED patients with (suspected) COVID-19.

We found no significant difference in PE-prevalence between patients with and without COVID-19, which is in line with several other studies. 8, 9 Since these studies mainly included patients with respiratory symptoms, alternative causes of their respiratory symptoms, including PE, should be present if COVID-19 was ruled out. Moreover, a report of the Danish population-based registry, mainly containing non-hospitalized patients, also showed that VTE risks in COVID-19 patients were comparable to that in COVID-19-negative and influenza patients. 10 The first published studies on PE in COVID-19 were predominantly performed in ICU patients, which led to the assumption that PE is highly prevalent among COVID-19 patients. In contrast with these severely ill (ICU) patients, the PEprevalence is apparently much lower in (suspected) COVID-19 patients at presentation in the ED. J o u r n a l P r e -p r o o f Figure 1 

Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis

Clinical Management of Severe Acute Respiratory Infection When COVID-19 Is Suspected, World Health Organisation, Interim Guidance V 1.2

Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study

CO-RADS: A Categorical CT Assessment Scheme for Patients Suspected of Having COVID-19-Definition and Evaluation

Pulmonary Embolism in COVID-19: The Actual Prevalence Remains Unclear

Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study

Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients

Association between Covid-19 and Pulmonary Embolism (AC-19-PE study)

Association Between Pulmonary Embolism and COVID-19 in Emergency Department Patients Undergoing Computed Tomography Pulmonary Angiogram: The PEPCOV International Retrospective Study

Venous thromboembolism and major bleeding in patients with COVID-19: A nationwide population-based cohort study