D-Dimer Levels as a Predictive Marker of Pulmonary Embolism in COVID-19 Patients

Namirah Iftikhar; Osama Rehman Khalid; Asif Husain Osmani; Uzma Ghori; Ashar Ekhlaq Ahmed

doi:10.36283/PJMD13-3/011

Authors

Namirah Iftikhar Ziauddin Hospital ,Karachi, Pakistan
Osama Rehman Khalid Ziauddin Hospital ,Karachi, Pakistan
Asif Husain Osmani Ziauddin Hospital ,Karachi, Pakistan
Uzma Ghori Ziauddin Hospital ,Karachi, Pakistan
Ashar Ekhlaq Ahmed Ziauddin Hospital ,Karachi, Pakistan

DOI:

https://doi.org/10.36283/PJMD13-3/011

Keywords:

Coronavirus Disease 2019, Thromboembolisms, Pulmonary, D-dimer.

Abstract

Background: COVID-19 infections have a higher risk of thrombotic complications due to a pro-inflammatory environment. This study aimed to find the association of D-dimer levels with pulmonary embolism (PE) and assess D-dimer levels as a predictive marker of PE in COVID-19 patients.

Methods: This prospective cross-sectional study was conducted from June to December 2021, at a private tertiary care teaching hospital in Karachi. Hospitalized COVID-19 patients with CTPA for PE, aged ≥18 years were selected through purposive sampling. With SPSS v.21, the association of co-morbidities and D-dimer levels for pulmonary embolism was analyzed using a t-test, chi-square test, and regression analysis while the predictive value of D-dimer levels for pulmonary embolism was analyzed using ROC analysis.

Results: Participants (337), median age:50yrs, IQR:48-70(52.2% males, 47.8% females). The majority (96.7%) were receiving prophylactic anticoagulant therapy, Median D-dimer levels were 1380(IQR:800-2100). Pulmonary Embolism was found in 46(13.6%), had a significant association with disease duration >5days (p=0.01), D-dimer levels >2200(p<0.001), smoking status (p<0.001), heart disease history (p=0.007), functional status (p=0.009), and chronic kidney disease (p=0.007). ROC curve analysis showed the 2285ng/ml D-dimers and maximum Youden Index,0.636. The D-dimer value had 80%sensitivity, 80%specificity, 38.6%PPV, 96.21%NPV, and 80%diagnostic accuracy. The average cumulative D-dimer value of 2300ng/ml, during admission had a 0.824 Youlden index with 97%sensitivity and 84%specificity. This cutoff was 48.83%PPV, 99.4%NPV, and 85.7%diagnostic accuracy.

Conclusion: Pulmonary Embolism was found in 13.6%(46/337). D-dimer levels >2285ng/ml have 80% diagnostic accuracy for pulmonary embolism. Larger multicentre studies are warranted to explore thrombo-prophylaxis indications, drug choice, and dosing based on D-dimer levels.

Keywords: COVID-19, Thromboembolism, Pulmonary, D-dimer

Author Biographies

Namirah Iftikhar, Ziauddin Hospital ,Karachi, Pakistan

Medicine Department
Osama Rehman Khalid, Ziauddin Hospital ,Karachi, Pakistan

Assistant professor, Internal Medicine Department
Asif Husain Osmani, Ziauddin Hospital ,Karachi, Pakistan

Oncology and Medicine Department
Uzma Ghori, Ziauddin Hospital ,Karachi, Pakistan

Professor and HOD, Internal Medicine Department
Ashar Ekhlaq Ahmed, Ziauddin Hospital ,Karachi, Pakistan

HOD Rheumatology

References

Laouan Brem F, Asmae B, Amane Y, Bouazzaoui MA, Chaymae M, Rasras H, Nasri S, Abda N, Skiker I, Kouismi H, Zakaria B, Ismaili N, El Ouafi N. Diagnostic Accuracy of D-Dimers for Predicting Pulmonary Embolism in COVID-19-Patients. Clin Appl Thromb Hemost. 2021;27:10760296211057901. doi: 10.117/10760296211057901.

Bukhari ZM, Alqarni MS, Abukhodair AW, Alzahrani AS, Alzahrani A, Alsrhani H, Alasadi F, Alotaibi AM, Althobaiti M. COVID-19-Related Pulmonary Embolism: Incidence, Characteristics, and Risk Factors. Cureus. 2021;13(11):e19738. doi: 10.7759/cureus.19738.

Kwee RM, Adams HJA, Kwee TC. Pulmonary embolism in patients with COVID-19 and value of D-dimer assessment: a meta-analysis. Eur Radiol. 2021;31(11):8168-8186. doi: 10.1007/s00330-021-08003-8.

Jevnikar M, Sanchez O, Chocron R, Andronikof M, Raphael M, Meyrignac O, Fournier L, Montani D, Planquette B, Soudani M, Boucly A, Pichon J, Preda M, Beurnier A, Bulifon S, Seferian A, Jaïs X, Sitbon O, Savale L, Humbert M, Parent F. Prevalence of pulmonary embolism in patients with COVID-19 at the time of hospital admission. Eur Respir J. 2021;58(1):2100116. doi: 10.1183/13993003.00116-2021.

Sakr Y, Giovini M, Leone M, Pizzilli G, Kortgen A, Bauer M, Tonetti T, Duclos G, Zieleskiewicz L, Buschbeck S, Ranieri VM, Antonucci E. Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review. Ann Intensive Care. 2020;10:124. doi: 10.1186/s13613-020-00741-0.

Artifoni M, Danic G, Gautier G, et al. Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors. Journal of Thrombosis and Thrombolysis 2020;50(1):211–216. doi: 10.1007/s11239-020-02146-z.

Bavaro DF, Poliseno M, Scardapane A, et al. Occurrence of acute pulmonary embolism in COVID-19—a case series. International Journal of Infectious Diseases 2020;98:225–226. doi: 10.1016/j.ijid.2020.06.066

Benito N, Filella D, Mateo J, et al. Pulmonary thrombosis or embolism in a large cohort of hospitalized patients with COVID-19. Frontiers in Medicine 2020;25(7):557. doi: 10.3389/fmed.2020.00557

Chen J, Wang X, Zhang S, et al. Characteristics of acute pulmonary embolism in patients with COVID-19 associated pneumonia from the city of Wuhan.Clinical and applied thrombosis-hemostasis 2020;26 1076029620936772.doi: 10.1177/1076029620936772

Léonard-Lorant I, Delabranche X, Séverac F, et al. Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels. Radiology 2020;296(3):E189–E191.

Ventura-Diaz S, Quintana-Pérez JV, Gil-Boronat A, et al. A higher D-dimer threshold for predicting pulmonary embolism in patients with COVID-19: a retrospective study. Emerg Radiol. 2020;27(6):679-689. JAMA 2020;324(8):799–801. doi: 10.1001/jama.2020.13372 .

Zhang L, Feng X, Zhang D, et al. Deep vein thrombosis in hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: prevalence, risk factors, and outcome. Circulation. 2020;142(2):114–128.

Suh YJ, Hong H, Ohana M, Bompard F, Revel MP, Valle C, Gervaise A, Poissy J, Susen S, Hékimian G, Artifoni M, Periard D, Contou D, Delaloye J, Sanchez B, Fang C, Garzillo G, Robbie H, Yoon SH. Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis. Radiology. 2021;298(2):E70-E80. doi: 10.1148/radiol.2020203557.

Wu T, Zuo Z, Yang D, Luo X, Jiang L, Xia Z, Xiao X, Liu J, Ye M, Deng M. Venous thromboembolic events in patients with COVID-19: a systematic review and meta-analysis. Age Ageing. 2021;50(2):284-293. doi: 10.1093/ageing/afaa259.

Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, Li Q, Jiang C, Zhou Y, Liu S, Ye C, Zhang P, Xing Y, Guo H, Tang W. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020;81(2):e16-e25. doi: 10.1016/j.jinf.2020.04.021.

Ooi MWX, Rajai A, Patel R, Gerova N, Godhamgaonkar V, Liong SY. Pulmonary thromboembolic disease in COVID-19 patients on CT pulmonary angiography - Prevalence, pattern of disease and relationship to D-dimer. Eur J Radiol. 2020;132:109336. doi: 10.1016/j.ejrad.2020.109336.

Pandey P, Agarwal S, Rajkumar. Lung Pathology in COVID-19: A Systematic Review. Int J Appl Basic Med Res. 2020;10(4):226-233. doi: 10.4103/ijabmr.IJABMR_381_20.

Bompard F, Monnier H, Saab I, Tordjman M, Abdoul H, Fournier L, Sanchez O, Lorut C, Chassagnon G, Revel MP. Pulmonary embolism in patients with COVID-19 pneumonia. Eur Respir J. 2020;56(1):2001365. doi: 10.1183/13993003.01365-2020.

Kirsch B, Aziz M, Kumar S, Burke M, Webster T, Immadi A, Sam M, Lal A, Estrada-Y-Martin RM, Cherian S, Aisenberg GM. Wells Score to Predict Pulmonary Embolism in Patients with Coronavirus Disease 2019. Am J Med. 2021;134(5):688-690. doi: 10.1016/j.amjmed.2020.10.044.

Melazzini F, Reduzzi M, Quaglini S, Fumoso F, Lenti MV, Di Sabatino A. Diagnostic Delay of Pulmonary Embolism in COVID-19 Patients. Front Med (Lausanne). 2021;8:637375. doi: 10.3389/fmed.2021.637375.

Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, Schneider F, Labani A, Bilbault P, Molière S, Leyendecker P, Roy C, Ohana M. Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels. Radiology. 2020;296(3):E189-E191. doi: 10.1148/radiol.2020201561.

Ceriani E, Combescure C, Le Gal G, Nendaz M, Perneger T, Bounameaux H, Perrier A, Righini M. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost. 2010;8(5):957-70. doi: 10.1111/j.1538-7836.2010.03801.x.

Gervaise A, Bouzad C, Peroux E, Helissey C. Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department. Eur Radiol. 2020;30(11):6170-6177. doi: 10.1007/s00330-020-06977-5.

Chi G, Lee JJ, Jamil A, Gunnam V, Najafi H, Memar Montazerin S, Shojaei F, Marszalek J. Venous Thromboembolism among Hospitalized Patients with COVID-19 Undergoing Thromboprophylaxis: A Systematic Review and Meta-Analysis. J Clin Med. 2020;9(8):2489. doi: 10.3390/jcm9082489.

Choi JJ, Wehmeyer GT, Li HA, Alshak MN, Nahid M, Rajan M, Liu B, Schatoff EM, Elahjji R, Abdelghany Y, D'Angelo D, Crossman D, Evans AT, Steel P, Pinheiro LC, Goyal P, Safford MM, Mints G, DeSancho MT. D-dimer cut-off points and risk of venous thromboembolism in adult hospitalized patients with COVID-19. Thromb Res. 2020;196:318-321. doi: 10.1016/j.thromres.2020.09.022.