A comparative analysis of the diagnostic performances of four clinical probability models to rule out pulmonary embolism

Abstract Funding Acknowledgements Type of funding sources: None. Background Ruling out pulmonary embolism (PE) through a combination of clinical assessment and Ddimer is crucial to avoid excessive computed tomography pulmonary angiography (CTPA), and different algorithms should be considered as an alternative to the fixed cutoff to achieve that goal. Purpose To compare diagnostic performance of 4 algorithms to rule out PE: fixed Ddimer cutoff, age-adjusted, YEARS and PEGeD. Methods Retrospective study of consecutive outpatients who presented to the emergency department and underwent CTPA for PE suspicion from April 2019 to May 2020. In fixed and age-adjusted cut-off, high probability patients are directly selected for CTPA. Low to moderate probability patients perform CTPA if Ddimer ≥500µg/L in fixed cutoff, and in age-adjusted cutoff if Ddimer ≥500µg/L in patients who are ≤ 50 years of age, and if Ddimer level was more than 10 times the patient’s age in patients older than 50 years. YEARS includes 3 items (signs of deep vein thrombosis, haemoptysis and whether PE is the most likely diagnosis): patients without any YEARS items and Ddimer ≥1000ng/mL or with ≥1 items and Ddimer 500ng/mL perform CTPA. In the PEGeD, patients with high clinical probability or with intermediate and Ddimers >500µg/L or low probability and Ddimer >1000 µg/L are selected for CTPA. Results We enrolled 571 patients and PE was confirmed by CTPA in 172. Compared with a fixed Ddimer cutoff, age-adjusted was associated with a significant increase of specificity (p < 0.001), correctly avoiding 38 CTPAs, without losing sensitivity. YEARS and PEGED resulted in a increase in specificity, compared to the fixed cutoff, but with an impairment of sensitivity (p < 0.001). PEGeD had the worst sensitivity (13 more false negatives (FN) than the fixed cutoff). Despite the lack of difference between PEGed and YEARS strategies regarding sensitivity, PEGED had a significantly higher specificity (p < 0.001) and allowed to correctly avoid a higher number of CTPA (95 vs 85), compared to the fixed cutoff. Conclusion Compared to fixed d-dimer cutoff, all algorithms were associated with an increased specificity. Age-adjusted cutoff was the only that is not associated with a significant decrease in sensitivity when compared to fixed cutoff, allowing to safely reduce the need to perform CTPA. Sen(%)Spec(%)Correctly avoid CTPAs(n)FN(n)Fixed cutoff251017Age-adjusted933513912YEARS894718619PEGED884919620

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Best approach in d-dimer algorithm to exclude pulmonary thromboembolism: a comparative study

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.250 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

BV Silva ◽

J Rigueira ◽

I Aguiar Ricardo ◽

C Mendonca ◽

P Alves Da Silva ◽

...

Keyword(s):

Clinical Decision ◽

Pulmonary Angiography ◽

Vein Thrombosis ◽

Funding Sources ◽

Clinical Probability ◽

Low Probability ◽

Sensitivity Specificity ◽

Deep Vein ◽

D Dimer ◽

Rule Out

Abstract Funding Acknowledgements Type of funding sources: None. Background Ruling out pulmonary embolism (PE) through a combination of clinical assessment and Ddimer is crucial to avoid excessive computed tomography pulmonary angiography (CTPA), and different algorithms should be considered as an alternative to the fixed cutoff to achieve that goal. Purpose To compare sensitivity, specificity, and reduction in CTPA requests of 4 algorithms to rule out PE: fixed Ddimer cutoff, age-adjusted, YEARS and PEGeD. Methods Retrospective study of consecutive outpatients who presented to the emergency department and underwent CTPA for PE suspicion from April 2019 to February 2020. The clinical-decision algorithms were retrospectively applied. In fixed and age-adjusted cutoffs, high probability patients are directly selected for CTPA and the others perform CTPA if Ddimer ≥500µg/L or age x10 µg/L within patients over 50 years, respectively. YEARS includes 3 items (signs of deep vein thrombosis, haemoptysis and whether PE is the most likely diagnosis): patients without any YEARS items and Ddimer ≥1000ng/mL or with ≥1 items and Ddimer 500ng/mL perform CTPA. In the PEGeD, patients with high clinical probability or with intermediate and Ddimers >500µg/L or low probability and Ddimer >1000 µg/L are selected for CTPA. Results We enrolled 409 patients and PE was confirmed by CTPA in 125 patients. Compared with a fixed Ddimer cutoff, age-adjusted was associated with a significant increased of specificity (p < 0.001), correctly avoiding 29 CTPAs, without losing sensitivity. YEARS resulted in a marked increase in specificity, compared to the fixed cutoff, but with an impairment of sensitivity(p = 0.002). PEGeD had the worst sensitivity, associated with 11 more false negatives (FN) than the fixed cutoff. Despite the lack of difference between PEGed and YEARS strategies regarding sensitivity, YEARS had a significantly higher specificity (p < 0.001) and allowed to correctly avoid a higher number of CTPA(55 vs 63), compared to the fixed cutoff. Results are summarized in table 1. Conclusion Compared to fixed d-dimer cutoff, all algorithms were associated with an increased specificity. Age-adjusted cutoff was the only that is not associated with a significant decrease in sensitivity when compared to fixed cutoff, allowing to safely reduce the need to perform CTPA. Sens(%) Spec(%) Correctly avoid CTPAs(n) FN(n) Fixed cutoff 95 29 85 6 Age-adjusted 93 40 114 9 YEARS 87 52 148 16 PEGeD 86 49 140 17

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Diagnosis of acute pulmonary embolism and evolving imaging modalities

ESC CardioMed ◽

10.1093/med/9780198784906.003.0659_update_001 ◽

2018 ◽

pp. 2761-2766

Author(s):

Helia Robert-Ebadi ◽

Grégoire Le Gal ◽

Marc Righini

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Angiography ◽

Thoracic Imaging ◽

Diagnostic Strategies ◽

Computed Tomographic ◽

Vein Thrombosis ◽

Clinical Probability ◽

Venous Compression ◽

Computed Tomographic Pulmonary Angiography ◽

Deep Vein

Modern non-invasive diagnostic strategies for pulmonary embolism rely on the sequential use of clinical probability assessment, D-dimer measurement, and thoracic imaging tests. Planar ventilation/perfusion scintigraphy was the cornerstone test for the diagnosis of pulmonary embolism for more than two decades and has now been replaced by computed tomographic pulmonary angiography (CTPA). Diagnostic strategies using CTPA are very safe to rule out pulmonary embolism and have been well validated in large prospective management outcome studies. Venous compression ultrasonography is the cornerstone test to diagnose deep vein thrombosis but is not mandatory for the diagnosis of pulmonary embolism when using multidetector CTPA.

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Diagnosis of acute pulmonary embolism and evolving imaging modalities

ESC CardioMed ◽

10.1093/med/9780198784906.003.0659 ◽

2018 ◽

pp. 2761-2766

Author(s):

Helia Robert-Ebadi ◽

Grégoire Le Gal ◽

Marc Righini

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Angiography ◽

Thoracic Imaging ◽

Diagnostic Strategies ◽

Computed Tomographic ◽

Vein Thrombosis ◽

Clinical Probability ◽

Venous Compression ◽

Computed Tomographic Pulmonary Angiography ◽

Deep Vein

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Diagnostic performance of complete lower limb venous ultrasound in patients with clinically suspected acute pulmonary embolism

Thrombosis and Haemostasis ◽

10.1160/th03-05-0278 ◽

2004 ◽

Vol 91 (01) ◽

pp. 187-195 ◽

Cited By ~ 41

Author(s):

Daniel Colombier ◽

Gérard Victor ◽

Marie Elias ◽

Catherine Arnaud ◽

Henri Juchet ◽

...

Keyword(s):

Pulmonary Embolism ◽

Sensitivity And Specificity ◽

Lower Limb ◽

Acute Pulmonary Embolism ◽

Pulmonary Angiography ◽

Helical Computed Tomography ◽

Diagnostic Strategies ◽

Vein Thrombosis ◽

Clinical Probability ◽

Deep Vein

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.

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Pulmonary embolism during the COVID-19 pandemic

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.183 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

BV Silva ◽

T Rodrigues ◽

N Cunha ◽

J Brito ◽

P Alves Da Silva ◽

...

Keyword(s):

Physical Activity ◽

Pulmonary Embolism ◽

Hospital Admissions ◽

Reference Group ◽

Group Versus ◽

Pulmonary Angiography ◽

Reference Period ◽

Funding Sources ◽

Clinical Probability

Abstract Funding Acknowledgements Type of funding sources: None. Background During the COVID-19 pandemic many countries have imposed lockdown restrictions to movement. Since the 18th of March in Portugal, thousands of people have been confined to their homes. While hospital admissions for COVID-19 patients increased exponentially, admissions for non-COVID-19 patients decreased dramatically. However, it remains unclear whether lockdown-related immobility can contribute to the increased incidence of pulmonary embolism. Purpose To compare the incidence of pulmonary embolism (PE) during the lockdown period (Abril 1 to May 31, 2020) compared to the reference period in 2019. Methods Retrospective study of consecutive outpatients who presented to the emergency department and underwent computed tomography pulmonary angiography (CTPA) due to suspicion of PE. Results Compared to the same period of 2019, the lockdown period was associated with a significant increase in PE diagnosis (29 versus 18 patients). PE patients during lockdown were older (median age 71 years; interquartile range [IQR][60-85] versus 59 years [44-76]; p = 0.046) and have lower prevalence of active cancer (14% versus 33% in the reference period). Women represent 55% (n = 16) of patients in lockdown group (versus 50% in 2019 group). Clinical probability (GENEVA score) was similar in both groups (median score 2.72 in lockdown group and 2.50 in reference group, p = 0.452). None of the patients with PE was diagnosed with COVID-19. Conclusion We have observed a marked increase (62%) in PE diagnosis during lockdown period compared to the reference period, which can be explained by the reduction in physical activity due to teleworking and closure of gyms and sports activities. These data reinforce the importance of promoting physical activity programs at home. The role of pharmacological or mechanical thromboprophylaxis in this scenario remains unclear.

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Performance of five D-dimer assays for the exclusion of symptomatic distal leg vein thrombosis

Thrombosis and Haemostasis ◽

10.1160/th11-07-0511 ◽

2012 ◽

Vol 107 (02) ◽

pp. 369-378 ◽

Cited By ~ 14

Author(s):

Jan Schwonberg ◽

Carola Hecking ◽

Marc Schindewolf ◽

Dimitrios Zgouras ◽

Susanne Lehmeyer ◽

...

Keyword(s):

High Sensitivity ◽

Diagnostic Value ◽

Vein Thrombosis ◽

Clinical Probability ◽

Wells Score ◽

Deep Vein ◽

Test Result ◽

D Dimer ◽

Rule Out ◽

Compression Ultrasonography

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.

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Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th17-03-0182 ◽

2017 ◽

Vol 117 (10) ◽

pp. 1937-1943 ◽

Cited By ~ 9

Author(s):

Jim Julian ◽

Lori-Ann Linkins ◽

Shannon Bates ◽

Clive Kearon ◽

Sarah Takach Lapner

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Diagnostic Accuracy ◽

Blood Samples ◽

Vein Thrombosis ◽

Clinical Probability ◽

Deep Vein ◽

New Strategies ◽

D Dimer

SummaryTwo new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7%) and the age-adjusted strategy (99.6%) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1% vs, 50.9%; difference 5.2%; 95% CI 3.5% to 6.8%). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.

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Correlation between the site of pulmonary embolism and the extent of deep vein thrombosis: evaluation by computed tomography pulmonary angiography and computed tomography venography

Japanese Journal of Radiology ◽

10.1007/s11604-010-0533-y ◽

2011 ◽

Vol 29 (3) ◽

pp. 171-176 ◽

Cited By ~ 5

Author(s):

Yosuke Horii ◽

Norihiko Yoshimura ◽

Yoshiro Hori ◽

Satoshi Takaki ◽

Toru Takano ◽

...

Keyword(s):

Computed Tomography ◽

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Pulmonary Angiography ◽

Computed Tomography Pulmonary Angiography ◽

Vein Thrombosis ◽

Deep Vein ◽

Computed Tomography Venography

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CASE OF SUCCESSFUL TREATMENT OF PULMONARY EMBOLISM WITH INVASIVE METHODS

Clinical Practice ◽

10.17816/clinpract1422-25 ◽

2010 ◽

Vol 1 (4) ◽

pp. 22-25

Author(s):

Yu M Alekseeva ◽

V I Potievskaya ◽

D P Lebedev ◽

E V Agagulyan

Keyword(s):

Pulmonary Embolism ◽

Surgical Intervention ◽

Pulmonary Angiography ◽

Right Ventricular Failure ◽

Ventricular Failure ◽

Vein Thrombosis ◽

Non Invasive ◽

Surgical Methods ◽

Deep Vein ◽

Anticoagulant Medication

This research is devoted to analyzing of the case of pulmonary embolism in a young woman with deep vein thrombosis taking oral contraceptives and successfully treated by surgical methods. Pulmonary angiography performed in patient L. allowed to confirm the diagnosis ofpulmonary embolism and reveal the localization of the thrombus. The treatment included selective thrombolysis by actilyse through catheter in the pulmonary artery. The treatment was not only non-invasive but included surgical intervention. Using of invasive methods, thrombolysis and anticoagulant medication allowed to stabilize the condition of the patient and prevent development of right ventricular failure.

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Physician and Patient Beliefs and Preferences in Pulmonary Embolism and Deep Vein Thrombosis Testing in People with Cancer

Blood ◽

10.1182/blood-2021-153688 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4265-4265

Author(s):

Anna Tran ◽

Kerstin De Wit ◽

Darshana Seeburruth

Keyword(s):

Pulmonary Embolism ◽

Diagnostic Imaging ◽

Cancer Patients ◽

Evidence Based ◽

Vein Thrombosis ◽

Clinical Probability ◽

Wells Score ◽

Low Threshold ◽

Deep Vein ◽

D Dimer

Abstract Introduction It is unclear whether evidence-based diagnostic protocols are followed when cancer patients are tested for venous thromboembolism (VTE). Evidence-based protocols reduce unnecessary diagnostic imaging, offer a patient-centered approach, and have the potential to standardize practice across medical specialties and settings. However, anecdote suggests that specialists who test people with cancer for VTE may prefer diagnostic imaging over clinical probability scoring and D-dimer testing. The aim of this study was to identify physician and patient knowledge, beliefs, values and preferences for VTE testing in cancer. This study was part of a program of research to set International Society of Thrombosis and Haemostasis standards for VTE testing in people with cancer. Methods This was an international qualitative interview study following COREQ guidelines. Semi-structured interviews with physicians and cancer patients were conducted via Zoom. We used purposive sampling to ensure inclusion of physicians from all specialties who test people with cancer for VTE, practicing across all continents. We invited people treated for cancer who had and did not have experience of VTE testing. We used grounded theory to create a conceptual framework which explains physician and patient values and preferences for VTE testing. Transcripts were coded by three researchers independently, who met to discuss their findings and agree on common codes. Researchers were a Thrombosis physician and two undergraduate students who ensured reflexivity was incorporated into their analysis. Results A total of 32 physicians and 6 cancer patients were invited to interview. Of those invited, 23 physicians and 6 patients across 6 continents completed an interview. Interviews lasted between 21 and 86 minutes. Our derived conceptual model can be seen in the attached Figure. Physicians reported a low threshold to test for VTE in people with cancer compared to those without cancer, because VTE was considered a fatal disease and highly prevalent in this patient population. Imaging was generally the only test used for VTE testing in cancer patients. Many participants relied on their Gestalt estimation of VTE probability when deciding whether to order imaging for pulmonary embolism or deep vein thrombosis. Most thought that low Wells score in combination with a negative D-dimer was not sufficiently sensitive to exclude VTE and anticipated the Wells score and D-dimer to be elevated. The Wells scores had poor face validity because they do not include cancer-specific variables and participants hoped to see a more nuanced formal score for VTE testing in cancer patients. Participants believed that their colleagues would support their diagnostic approach. Patients reported they were used to having tests and CT scans. Patients felt it was important for their physicians to prioritize testing for VTE. Patients had full trust and confidence in their physicians' testing decisions, particularly in decisions made by their oncologists. Conclusion Physicians have a low threshold to test people with cancer for VTE and tend not to use clinical probability assessment and D-dimer. Patients are comfortable having diagnostic imaging, feel VTE testing is important and have full trust in their physicians. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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