We read with great interest the manuscript published by Klok and colleagues which highlight important aspects regarding the occurrence of venous thromboembolism (VTE) in patients with COVID-19 infections hospitalized in intensive care unit (ICU) [1]. The investigation reported a higher risk of thrombotic complications in COVID-patients with severe disease hospitalized in ICU. Notably, age-adjusted hazard ratio and coagulopathy, defined, as spontaneous prolongation of the prothrombin time >3 s or activated partial thromboplastin time >5 s resulted independent predictors of thrombotic complications. Regarding the venous thrombotic events, no data regarding which type of clinical pre-test probability was used to suspect VTE. Moreover, no data regarding the D-dimer level assessment were provided. It would be of interest to know if the D-dimer level was evaluated using a fix or an age adjusted cut-off. Indeed, as reported by other recent investigations and national surveillance programs, the mortality rate as well as the severe forms of COVID-19 pneumonia increase with aging [2]. For these reasons, it seems reasonable to prefer the adoption of an age-adjusted cut-off in these subjects. Moreover, it has already been demonstrated by several studies and meta-analysis that the age-adjusted threshold can reduce the need for imaging tests compared to a fixed cut-off [[3], [4], [5], [6], [7], [8]]. This aspect could be very useful in COVID-19 subjects, limiting the need for CUS and/or to transfer an infectious patient to the radiology ward to perform an unnecessary computed tomography pulmonary angiography (CTPA) to exclude PE. Further studies are needed to assess the clinical features and prognostic implications of VTE in COVID-19 patients to further improve their thromboprophylaxis and diagnostic management. However, the VTE is emerging as an important complication in COVID-19 patients that must be not underestimated.
Funding
None.
Declaration of competing interest
None of the authors have conflicts of interest to declare.
References
- 1.Klok F.A., Kruip M.J.H.A., van der Meer N.J.M., Arbous M.S., Gommers D.A.M.P.J., Kant K.M., Kaptein F.H.J., van Paassen J., Stals M.A.M., Huisman M.V., Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020 doi: 10.1016/j.thromres.2020.04.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Onder G., Rezza G., Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 doi: 10.1001/jama.2020.4683. [Epub ahead of print] [DOI] [PubMed] [Google Scholar]
- 3.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., Van Kralingen K.W., Grootenboers M.J., Durian M.F., Cheung Y.W., Meyer G., Bounameaux H., Huisman M.V., Kamphuisen P.W., Le Gal G. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014;311:1117–1124. doi: 10.1001/jama.2014.2135. [DOI] [PubMed] [Google Scholar]
- 4.Gómez-Jabalera E., Bellmunt Montoya S., Fuentes-Camps E., Escudero Rodríguez J.R. Age-adjusted D-dimer for the diagnosis of deep vein thrombosis. Phlebology. 2018;33:458–463. doi: 10.1177/0268355517718762. [DOI] [PubMed] [Google Scholar]
- 5.Nybo M., Hvas A.M. Age-adjusted D-dimer cut-off in the diagnostic strategy for deep vein thrombosis: a systematic review. Scand. J. Clin. Lab. Invest. 2017;77:568–573. doi: 10.1080/00365513.2017.1390783. [DOI] [PubMed] [Google Scholar]
- 6.Schouten H.J., Geersing G.J., Koek H.L., Zuithoff N.P., Janssen K.J., Douma R.A., van Delden J.J., Moons K.G., Reitsma J.B. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ. 2013;346:f 2492. doi: 10.1136/bmj.f2492. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.van Es N., van der Hulle T., van Es J., den Exter P.L., Douma R.A., Goekoop R.J., Mos I.C., Galipienzo J., Kamphuisen P.W., Huisman M.V., Klok F.A., Büller H.R., Bossuyt P.M. Wells rule and D-Dimer testing to rule out pulmonary embolism: a systematic review and individual-patient data meta-analysis. Ann. Intern. Med. 2016;165:253–261. doi: 10.7326/M16-0031. [DOI] [PubMed] [Google Scholar]
- 8.Konstantinides S.V., Meyer G., Becattini C., Bueno H., Geersing G.J., Harjola V.P., Huisman M.V., Humbert M., Jennings C.S., Jiménez D., Kucher N., Lang I.M., Lankeit M., Lorusso R., Mazzolai L., Meneveau N., Ní Áinle F., Prandoni P., Pruszczyk P., Righini M., Torbicki A., Van Belle E., Zamorano J.L., ESC Scientific Document Group 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) Eur Heart J. 2020;41:543–603. doi: 10.1093/eurheartj/ehz405. [DOI] [PubMed] [Google Scholar]