WHY IS PULMONARY EMBOLISM STILL MISSED? CLINICAL PITFALLS, DIAGNOSTIC ERRORS AND CONTEMPORARY STRATEGIES FOR EARLY RECOGNITION - REVIEW
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6009Keywords:
Pulmonary Embolism; Diagnostic Delay; Misdiagnosis; D-Dimer; Clinical Decision Rules; Computed Tomography Pulmonary AngiographyAbstract
Pulmonary embolism (PE) remains a frequent, potentially fatal and persistently challenging diagnosis in emergency, inpatient and primary care settings. Although modern diagnostic pathways combine pre-test probability assessment, D-dimer testing and imaging, PE is still missed or diagnosed late because its presentation overlaps with pneumonia, chronic obstructive pulmonary disease exacerbation, acute coronary syndrome, heart failure, anxiety and other common conditions. This review synthesizes evidence on why PE continues to be under-recognized and how diagnostic pathways can be improved. The manuscript was developed on the basis of contemporary scientific literature, including clinical practice guidelines, clinical reviews, prospective studies, and studies evaluating diagnostic delay. The available evidence suggests that delayed recognition of pulmonary embolism is rarely caused solely by limited access to imaging studies. More often, it results from low initial clinical suspicion, atypical presentation, cognitive errors, inappropriate use of D-dimer testing, inconsistent application of clinical prediction rules, and limitations of imaging modalities.. Age-adjusted and clinical probability-adjusted D-dimer strategies, the YEARS algorithm and PEGeD approach reduce unnecessary imaging while maintaining diagnostic safety in selected patients. Future improvement depends on combining disciplined bedside reasoning with validated algorithms, targeted use of imaging, clinician education, and carefully evaluated artificial intelligence or electronic health record decision-support tools.
References
Banerjee, I., Sofela, M., Yang, J., Chen, J. H., Shah, N. H., Ball, R. L., Mushlin, A. I., Desai, M., Bledsoe, J., Amrhein, T., Rubin, D. L., Zamanian, R., & Lungren, M. P. (2019). Development and performance of the Pulmonary Embolism Result Forecast Model (PERFORM) for computed tomography clinical decision support. JAMA Network Open, 2(8), e198719. https://doi.org/10.1001/jamanetworkopen.2019.8719
Dobler, C. C. (2019). Overdiagnosis of pulmonary embolism: Definition, causes and implications. Breathe, 15(1), 46–53. https://doi.org/10.1183/20734735.0339-2018
Farzaei, A., Farzaei, M., Gholizadeh, H., Abolghasemi, S., Abdollahi, S., Rezazadeh, S., Shafeghat, T., Taherifard, E., Gholami, S., Baghaei, R., & Jalali, A. (2025). The role of artificial intelligence in diagnosing pulmonary embolism: A systematic review and meta-analysis. Archives of Academic Emergency Medicine, 13(1), e86. https://pubmed.ncbi.nlm.nih.gov/41664805/
Freund, Y., Cohen-Aubart, F., & Bloom, B. (2022). Acute pulmonary embolism: A review. JAMA, 328(13), 1336–1345. https://doi.org/10.1001/jama.2022.16815
Hassan, M. S. T. A., Sahu, A., Anthony, C., & Williams, M. C. (2025). The current state of artificial intelligence on detecting pulmonary embolism via computerized tomography pulmonary angiogram: A systematic review. British Journal of Hospital Medicine, 86(6), 1–14. https://doi.org/10.12968/hmed.2024.0757
Hendriksen, J. M. T., Koster-van Ree, M., Morgenstern, M. J., Oudega, R., Schutgens, R. E. G., Moons, K. G. M., & Geersing, G. J. (2017). Clinical characteristics associated with diagnostic delay of pulmonary embolism in primary care: A retrospective observational study. BMJ Open, 7(3), e012789. https://doi.org/10.1136/bmjopen-2016-012789
Jimenez, D., Agusti, A., Tabernero, E., Alcazar-Navarrete, B., Montiel, C., Zamora, J., Monreal, M., Pedrajas, J. M., Ballaz, A., Marti, D., Uresandi, F., Yusen, R. D., Barrios, D., & SLICE Investigators. (2021). Effect of a pulmonary embolism diagnostic strategy on clinical outcomes in patients hospitalized for COPD exacerbation: A randomized clinical trial. JAMA, 326(13), 1277–1285. https://doi.org/10.1001/jama.2021.14888
Kahn, S. R., & de Wit, K. (2022). Pulmonary embolism. New England Journal of Medicine, 387(1), 45–57. https://doi.org/10.1056/NEJMcp2116489
Kearon, C., de Wit, K., Parpia, S., Schulman, S., Afilalo, M., Hirsch, A., Spencer, F. A., Sharma, S., D'Aragon, F., Deshaies, J. F., Le Gal, G., Lazo-Langner, A., Wu, C., Rudd-Scott, L., Bates, S. M., Julian, J. A., & Rodger, M. A. (2019). Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. New England Journal of Medicine, 381(22), 2125–2134. https://doi.org/10.1056/NEJMoa1909159
Kline, J. A., Courtney, D. M., Kabrhel, C., Moore, C. L., Smithline, H. A., Plewa, M. C., Richman, P. B., O'Neil, B. J., & Nordenholz, K. (2008). Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. Journal of Thrombosis and Haemostasis, 6(5), 772–780. https://doi.org/10.1111/j.1538-7836.2008.02944.x
Kline, J. A., Hernandez-Nino, J., Jones, A. E., Rose, G. A., Norton, H. J., & Camargo, C. A., Jr. (2007). Prospective study of the clinical features and outcomes of emergency department patients with delayed diagnosis of pulmonary embolism. Academic Emergency Medicine, 14(7), 592–598. https://doi.org/10.1197/j.aem.2007.03.1356
Klok, F. A., Mos, I. C. M., Nijkeuter, M., Righini, M., Perrier, A., Le Gal, G., & Huisman, M. V. (2008). Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Archives of Internal Medicine, 168(19), 2131–2136. https://doi.org/10.1001/archinte.168.19.2131
Konstantinides, S. V., Meyer, G., Becattini, C., Bueno, H., Geersing, G. J., Harjola, V. P., Huisman, M. V., Humbert, M., Jennings, C. S., Jimenez, D., Kucher, N., Lang, I. M., Lankeit, M., Lorusso, R., Mazzolai, L., Meneveau, N., Ni Ainle, F., Prandoni, P., Pruszczyk, P., . . . Zamorano, J. L. (2020). 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). European Heart Journal, 41(4), 543–603. https://doi.org/10.1093/eurheartj/ehz405
Kwok, C. S., Wong, C. W., Lovatt, S., Myint, P. K., & Loke, Y. K. (2022). Misdiagnosis of pulmonary embolism and missed pulmonary embolism: A systematic review of the literature. Health Sciences Review, 3, 100022. https://doi.org/10.1016/j.hsr.2022.100022
Le Gal, G., Righini, M., Roy, P. M., Sanchez, O., Aujesky, D., Bounameaux, H., & Perrier, A. (2006). Prediction of pulmonary embolism in the emergency department: The revised Geneva score. Annals of Internal Medicine, 144(3), 165–171. https://doi.org/10.7326/0003-4819-144-3-200602070-00004
Makowska, A., Kosińska-Kaczyńska, K., & Szymusik, I. (2024). Pulmonary embolism in pregnancy: A review for clinical practitioners. Journal of Clinical Medicine, 13(10), 2863. https://doi.org/10.3390/jcm13102863
Mansella, G., Keil, C., Nickel, C. H., Eken, C., Wirth, C., Tzankov, A., Peterson, C. J., Aujesky, D., & Bingisser, R. (2020). Delayed diagnosis in pulmonary embolism: Frequency, patient characteristics, and outcome. Respiration, 99(7), 589–597. https://doi.org/10.1159/000508396
Masotti, L., Righini, M., Vuilleumier, N., Antonelli, F., Landini, G., Cappelli, R., & Ray, P. (2008). Pulmonary embolism in the elderly: A review on clinical, instrumental and laboratory presentation. Vascular Health and Risk Management, 4(3), 629–636. https://pmc.ncbi.nlm.nih.gov/articles/PMC2515422/
Ogdie, A. R., Reilly, J. B., Pang, W. G., Keddem, S., Barg, F. K., von Feldt, J. M., & Myers, J. S. (2012). Seen through their eyes: Residents' reflections on the cognitive and contextual components of diagnostic errors in medicine. Academic Medicine, 87(10), 1361–1367. https://doi.org/10.1097/ACM.0b013e31826742c9
Poenou, G., Chevret, S., & Carrier, M. (2022). Pulmonary embolism in the cancer associated thrombosis landscape. Cancers, 14(18), 4510. https://doi.org/10.3390/cancers14184510
Righini, M., van Es, J., den Exter, P. L., Roy, P. M., Verschuren, F., Ghuysen, A., Rutschmann, O. T., Sanchez, O., Jaffrelot, M., Trinh-Duc, A., Le Gall, C., Moustafa, F., Principe, A., van Houten, A. A., Ten Wolde, M., Douma, R. A., Hazelaar, G., Erkens, P. M. G., van Kralingen, K. W., . . . Le Gal, G. (2014). Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: The ADJUST-PE study. JAMA, 311(11), 1117–1124. https://doi.org/10.1001/jama.2014.2135
Righini, M., Robert-Ebadi, H., & Le Gal, G. (2024). Age-adjusted and clinical probability adapted D-dimer cutoffs to rule out pulmonary embolism: A narrative review of clinical trials. Journal of Clinical Medicine, 13(12), 3571. https://doi.org/10.3390/jcm13123571
Robert-Ebadi, H., Elias, A., Sanchez, O., Le Moigne, E., Schmidt, J., & Righini, M. (2022). Diagnosis of pulmonary embolism during pregnancy. Diagnostics, 12(8), 1875. https://doi.org/10.3390/diagnostics12081875
Sato, R., Hasegawa, D., Nishida, K., Takahashi, K., Schleicher, M., Chaisson, N. F., & McCormack, M. C. (2021). Prevalence of pulmonary embolism in patients with acute exacerbations of COPD: A systematic review and meta-analysis. American Journal of Emergency Medicine, 50, 606–617. https://doi.org/10.1016/j.ajem.2021.09.030
Soffer, S., Klang, E., Shimon, O., Barash, Y., Cahan, N., Greenspan, H., & Konen, E. (2021). Deep learning for pulmonary embolism detection on computed tomography pulmonary angiogram: A systematic review and meta-analysis. Scientific Reports, 11, 15814. https://doi.org/10.1038/s41598-021-95249-3
Te Haara, S. R., De Rezende, H., & Wang, C. (2024). Diagnostic test accuracy of the YEARS algorithm for pulmonary embolism: A systematic review and meta-analysis. Sultan Qaboos University Medical Journal, 1(1). https://doi.org/10.18295/squmj.1.2024.007
Teissandier, D., Roussel, M., Bannelier, H., Freund, Y., & Catoire, P. (2024). Contemporary approaches to pulmonary embolism diagnosis: A clinical review. Clinical and Experimental Emergency Medicine, 11(2), 127–135. https://doi.org/10.15441/ceem.23.157
Thomas, S. E., Goodacre, S., & Sampson, F. C. (2024). Diagnosis of pulmonary embolism: A review of evidence-based approaches. Journal of Clinical Medicine, 13(13), 3804. https://doi.org/10.3390/jcm13133804
Tromeur, C., van der Pol, L. M., Klok, F. A., Le Roux, P. Y., Ende-Verhaar, Y. M., Salaun, P. Y., Leroyer, C., Huisman, M. V., Couturaud, F., & van der Hulle, T. (2019). Computed tomography pulmonary angiography versus ventilation-perfusion lung scanning for diagnosing pulmonary embolism during pregnancy: A systematic review and meta-analysis. Haematologica, 104(1), 176–188. https://doi.org/10.3324/haematol.2018.196121
van der Hulle, T., Cheung, W. Y., Kooij, S., Beenen, L. F. M., van Bemmel, T., van Es, J., Faber, L. M., Hazelaar, G. M., Heringhaus, C., Hofstee, H. M. A., Hovens, M. M. C., Kaasjager, K., van Klink, R. C. J., Kruip, M. J. H. A., Loeffen, R. F., Mairuhu, A. T. A., Middeldorp, S., Nijkeuter, M., van der Pol, L. M., . . . Huisman, M. V. (2017). Simplified diagnostic management of suspected pulmonary embolism: The YEARS study. Lancet, 390(10091), 289–297. https://doi.org/10.1016/S0140-6736(17)30885-1
van der Pol, L. M., Bistervels, I. M., van Mens, T. E., van der Hulle, T., den Exter, P. L., Beenen, L. F. M., le Roux, P. Y., van Bemmel, T., van Es, J., Faber, L. M., Hofstee, H. M. A., Hovens, M. M. C., Kaasjager, K., Kruip, M. J. H. A., Mairuhu, A. T. A., Middeldorp, S., Nijkeuter, M., van der Meer, F. J. M., . . . Huisman, M. V. (2019). Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism. New England Journal of Medicine, 380(12), 1139–1149. https://doi.org/10.1056/NEJMoa1813865
van der Pol, L. M., Tromeur, C., Bistervels, I. M., Ni Ainle, F., van Bemmel, T., Bertoletti, L., Couturaud, F., van Dooren, Y. P. A., Elias, A., Faber, L. M., Hofstee, H. M. A., van der Hulle, T., Huisman, M. V., Klok, F. A., & Righini, M. (2018). The YEARS algorithm for suspected pulmonary embolism: Shorter visit time and reduced costs at the emergency department. Journal of Thrombosis and Haemostasis, 16(4), 725–733. https://doi.org/10.1111/jth.13972
van Maanen, R., Trinks-Roerdink, E. M., Rutten, F. H., & Geersing, G. J. (2022). A systematic review and meta-analysis of diagnostic delay in pulmonary embolism. European Journal of General Practice, 28(1), 165–172. https://doi.org/10.1080/13814788.2022.2086232
Vyas, V., & Goyal, A. (2024). Acute pulmonary embolism. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK560551/
Webster, C. S., Taylor, S., & Weller, J. M. (2021). Cognitive biases in diagnosis and decision making during anaesthesia and intensive care. BJA Education, 21(11), 420–425. https://doi.org/10.1016/j.bjae.2021.07.003
Wells, P. S., Anderson, D. R., Rodger, M., Ginsberg, J. S., Kearon, C., Gent, M., Turpie, A. G. G., Bormanis, J., Weitz, J., Chamberlain, M., Bowie, D., Barnes, D., & Hirsh, J. (2000). Derivation of a simple clinical model to categorize patients' probability of pulmonary embolism: Increasing the model's utility with the SimpliRED D-dimer. Thrombosis and Haemostasis, 83(3), 416–420. https://pubmed.ncbi.nlm.nih.gov/10744147/
Yao, D., Cao, W., & Liu, X. (2024). Clinical manifestations and misdiagnosis factors of pulmonary embolism patients seeking treatment in cardiology. Medicine, 103(49), e40821. https://doi.org/10.1097/MD.0000000000040821
Zhang, N. J., Rameau, P., Julemis, M., Liu, Y., Solomon, J., Khan, S., McGinn, T., & Richardson, S. (2022). Automated pulmonary embolism risk assessment using the Wells criteria: Validation study. JMIR Formative Research, 6(2), e32230. https://doi.org/10.2196/32230
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Copyright (c) 2026 Mateusz Gadzina, Emilia Koziara, Julia Gawlak, Zofia Tarnawska, Karolina Figiel, Mateusz Gawin, Wojciech Sontag, Mateusz Zawisza, Aleksandra Golec, Maciej Krzesimir Kuswik

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