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Vol. 220. Issue 7.
Pages 459-461 (October 2020)
Vol. 220. Issue 7.
Pages 459-461 (October 2020)
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Pulmonary embolism and COVID-19: A paradigm change
Tromboembolismo pulmonar y COVID-19: un cambio de paradigma
A. Franco-Moreno
Corresponding author
, N. Muñoz-Rivas, B. Mestre-Gómez, J. Torres-Macho
Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
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Tables (1)
Table 1. Case series of patients with COVID-19 and VTE.
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Dear Director,

On December 31, 2019, an outbreak of pneumonia caused by a novel coronavirus named SARS-CoV-2 was detected in the city of Wuhan (China). From a clinical point of view, infected patients could present with anything from mild upper respiratory tract symptoms to severe pneumonia associated with respiratory distress syndrome that could progress to severe respiratory failure and death of the patient.

Although this new disease mainly affects the respiratory tract, several observational studies suggest that SARS-CoV-2 (COVID-19) infection predisposes patients to thrombotic events in the vein; pulmonary embolism (PE) is the most frequent among them.1–7 This increase in pulmonary thrombotic manifestations has been observed in the autopsies of patients infected in the SARS-CoV and MERS-CoV epidemics of 2003 and 2012, respectively.8

The physiopathology that links PE and SARS-CoV-2 infection is not well known, though it seems to be related to a state of hypercoagulability. Recent studies have demonstrated that D-dimer levels greater than 1,000 ng/mL in patients with COVID-19 constitute a prognostic factor that is relevant to mortality.9 The systemic inflammatory response and endothelial damage associated with viral infection could activate coagulation, with an increase in thrombin generation and a decrease in the organism’s natural anticoagulants. Years ago, the term “immunothrombosis” was coined to describe this correlation between the immune system and the coagulation system as a response to infection designed to prevent its propagation.

SARS-CoV-2 penetrates alveolar epithelial cells through the angiotensin-converting enzyme 2 (ACE2) surface receptor.10 Viral replication triggers the activation of the complement system, with formation of C3a and C5a, which are able to recruit neutrophils, macrophages, lymphocytes, and monocytes that in turn are responsible for the massive release of proinflammatory cytokines (IL-1, IL-6, IL-8, and interferon-γ). These favor the expression of the tissue factor (TF) of thrombomodulin and endothelial adhesion molecules and also activate fibrinolysis, among other effects.11

Furthermore, SARS-CoV-2 infects endothelial cells that express ACE2. This endothelial damage activates the TF, which generates thrombin from prothrombin by means of activated factor X action. The activated circulating platelets coagulate and provide an appropriate phospholipid surface for the adhesion of different compounds in the coagulation cascade, with the generation of a large amount of thrombin.

Recently, Ciceri et al. have proposed the acronym MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) to designate this pulmonary thrombotic microangiopathy or thrombosis in situ.12 In concordance with this pathophysiological hypothesis, fibrin clots have been found in small pulmonary artery vessels in the autopsies of patients who have died due to COVID-19.13

For this reason, it would be interesting to learn the incidence of deep vein thrombosis (DVT) in patients with COVID-19 and PE. According to published series, the presence of concomitant DVT varies between 35%–45% in patients with PE.14 Though 20% of patients with PE can present with undiagnosed DVT, the studies by Poissy et al.4 and Lodigiani et al.6 observed an incidence of DVT of 13.6% and 10%, respectively, in patients with COVID-19 and PE. The published case series of patients with COVID-19 and DVT are shown in Table 1.

Table 1.

Case series of patients with COVID-19 and VTE.

Study  Number of patients  Study scope  Incidence of VTE (n; %)  Antithrombotic therapy regimen  Type of event 
Klok et al.1  184  ICU  26 (14.13)  Prophylactic heparin  25 patients with PE 
          One patient with DVT 
          Other: one DVT in the upper limb associated with a catheter and 3 strokes 
Llitjos et al.2  26  ICU  18 (69) with venous thrombosis in the LL and 6 (23) with PE  8 patients with prophylactic heparin  6 patients with PE 
        18 patients with therapeutic heparin  14 patients with DVT 
          4 patients with SVT 
Cui et al.3  81  ICU  20 (25)  Not administered  20 patients with DVT 
Poissy et al.4  107  ICU  22 (20.6) with PE and 5 (4.7) with DVT  20 patients with prophylactic heparin  22 patients with PE; 3 patients with concomitant DVT (13.6%) 
        One patient with VKA  5 patients with DVT 
        One patient with therapeutic heparin   
Lodigiani et al.5  388  ICU and HU  16 (4.4)  100% of ICU patients with prophylactic heparin  10 patients with PE; 1 patient with concomitant DVT (10%) 
        75% of HU patients with prophylactic heparin  4 patients with proximal DVT 
          One patient with distal DVT 
          Other: 1 DVT in the upper limb associated with a catheter, 9 strokes, and 4 ACS 
Helms et al.6  150  ICU  25 (16.7) with PE and 3 (2) with DVT  Prophylactic heparin  25 patients with PE 
          3 patients with DVT 
          Other: 2 strokes: one mesenteric ischemia and one peripheral artery ischemia 
Middeldorp et al.7  198  ICU and HU  39 (20)  Prophylactic heparin  13 patients with PE 
          14 patients with proximal DVT 
          11 patients with distal DVT 
          One patient with DVT in the upper limb 

VKA: vitamin K antagonist; LL: lower limbs; ACS: acute coronary syndrome; PE: pulmonary embolism; VTE: venous thromboembolism; DVT: deep vein thrombosis; SVT: superficial vein thrombosis; ICU: intensive care unit; HU: hospitalization unit.

In conclusion, the severe respiratory failure that patients with COVID-19 develop may partially be explained by pulmonary thrombotic microangiopathy that is the consequence of an exaggerated immune response in the host. The coagulopathy in these patients has led to the proposal of different antithrombotic strategies, especially in severe patients admitted to intensive care units (ICU). Although we do not know the best antithrombotic strategy, low-molecular-weight heparins at prophylactic or intermediate doses should be indicated in these patients (except when contraindicated). Therapeutic anticoagulation should be reserved for cases in which thrombosis is observed or suspected.15

Randomized controlled trials are needed to determine the suitability of primary thromboprophylaxis beyond discharge from the hospital and the optimal duration of anticoagulant treatment in patients with PE.

Conflicts of interest

The authors declare that they do not have any conflicts of interest.

F.A. Klok, M.J.H.A. Kruip, N.J.M. van der Meer, M.S. Arbous, D.A.M.P.J. Gommers, K.M. Kant, et al.
Incidence of thrombotic complications in critically ill ICU patients with COVID-19.
Thromb Res, 191 (2020), pp. 145-147
J.F. Llitjos, M. Leclerc, C. Chochois, J.M. Monsallier, M. Ramakers, M. Auvray, et al.
High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients.
J Thromb Haemost, (2020),
S. Cui, S. Chen, X. Li, S. Liu, F. Wang.
Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.
J Thromb Haemost, 18 (2020), pp. 1421-1424
J. Poissy, J. Goutay, M. Caplan, E. Parmentier, T. Duburcq, F. Lassalle, et al.
Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence.
C. Lodigiani, G. Iapichino, L. Carenzo, M. Cecconi, P. Ferrazzi, T. Sebastian, et al.
Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy.
J. Helms, C. Tacquard, F. Severac, I. Leonard-Lorant, M. Ohana, X. Delabranche, et al.
High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.
Intensive Care Med, 46 (2020), pp. 1089-1098
S. Middeldorp, M. Coppens, T.F. van Haaps, M. Foppen, A.P. Vlaar, M.C.A. Müller, et al.
Incidence of venous thromboembolism in hospitalized patients with COVID-19.
J Thromb Haemost, (2020),
D. Giannis, I.A. Ziogas, P. Gianni.
Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past.
J Clin Virol, 127 (2020),
N. Tang, H. Bai, X. Chen, J. Gong, D. Li, Z. Sun.
Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
J Thromb Haemost, 18 (2020), pp. 1094-1099
H. Zhang, J.M. Penninger, Y. Li, N. Zhong, A.S. Slutsky.
Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.
Intensive Care Med, 46 (2020), pp. 586-590
K. Yuki, M. Fujiogi, S. Koutsogiannaki.
COVID-19 pathophysiology: a review.
Clin Immunol, 215 (2020),
F. Ciceri, L. Beretta, A.M. Scandroglio, S. Colombo, G. Landoni, A. Ruggeri, et al.
Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis.
Crit Care Resusc, (2020),
L. Carsana, A. Sonzogni, A. Nasr, R. Rossi, A. Pellegrinelli, P. Zerbi, et al.
Pulmonary Post-Mortem Findings in a Series of COVID-19 Cases From Northern Italy: A Two-Centre Descriptive Study.
Lancet Infect Dis, (2020),
A.B. van Rossum, H.C. van Houwelingen, G.J. Kieft, P.M. Pattynama.
Prevalence of deep vein thrombosis in suspected and proven pulmonary embolism: a meta-analysis.
Br J Radiol, 71 (1998), pp. 1260-1265
B. Bikdeli, M.V. Madhavan, D. Jimenez, T. Chuich, I. Dreyfus, E. Driggin, et al.
COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up.
J Am Coll Cardiol, 75 (2020), pp. 2950-2973

Please cite this article as: Franco-Moreno A, Muñoz-Rivas N, Mestre-Gómez B, Torres-Macho J. Tromboembolismo pulmonar y COVID-19: un cambio de paradigma. Rev Clin Esp. 2020;220:459–461.

Copyright © 2020. Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)
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