High rate of pulmonary thromboembolism in patients with SARS-CoV-2 pneumonia

Minuz, Pietro; Mansueto, Giancarlo; Mazzaferri, Fulvia; Fava, Cristiano; Dalbeni, Andrea; Ambrosetti, Maria Chiara; Sibani, Marcella; Tacconelli, Evelina

doi:10.1016/j.cmi.2020.06.011

Cited by 11 publications

(13 citation statements)

References 5 publications

(7 reference statements)

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“…The clinical finding of high prevalence of pulmonary thrombosis in COVID-19 patients, 8 , 21 recently confirmed by autopsy identification of microvascular thrombosis in the areas of inflamed lungs, 5 prompted us to explore the contribution of platelets to this process. We considered the hypothesis that platelets could have a central role in the process of thromboinflammation in COVID-19, advanced on the basis of experimental models of septic and aseptic inflammation, as well as in human viral pneumonia.…”

Section: Discussionmentioning

confidence: 93%

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Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Taus

Salvagno

Canè

et al. 2020

ATVB

158

182

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Objective: Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism. Approach and Results: Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P <0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P <0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P =nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients ( P <0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P <0.001), showed accelerated factor XII–dependent coagulation. Conclusions: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

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Section: Discussionmentioning

confidence: 93%

“… 10 A radiological pneumonia severity score was used in COVID-19 patients, to obtain a semiquantitative assessment of lung disease in COVID-19, ranking the pulmonary involvement on an 18-point severity scale according to the extent and the characteristics of lung abnormalities. 21 …”

Section: Methodsmentioning

confidence: 99%

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Taus

Salvagno

Canè

et al. 2020

ATVB

158

182

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“…Discrepancies were resolved by consensus between two of the more experienced radiologists. Meiler et al [ 64 ] Germany March 1–April 20 -50 -Mean 60.4 years (± 10.1) -34 males NR NR Two junior radiologists with subspeciality training in thoracic radiology, and A senior thoracic radiologist (for equivocal cases) Mestre-Gómez et al [ 65 ] Spain March 30–April 12 -91 -Median 65 years -62 males Respiratory deterioration not attributable to other causes, data on acute respiratory distress without improvement despite specific treatment or elevation of D-dimer levels in discordance with other inflammatory parameters 23 of 29 patients with PE (≥ 25.3%) NR Minuz et al [ 66 ] Italy March 30–April 6 -10 -NR -NR Persistent respiratory impairment and a D-dimer value at least five times the upper reference limit. NR NR Mirsadraee et al [ 68 ] UK March 19–June 23 -72 -Mean 52 years (± 10) -53 males Routine in all patients who are admitted to ICU 12 patients (16.7%) Two consultant cardiothoracic radiologists, with disagreements resolved by consensus.…”

Section: Resultsmentioning

confidence: 99%

Pulmonary embolism in patients with COVID-19 and value of D-dimer assessment: a meta-analysis

Kwee

Adams²,

Kwee

2021

Eur Radiol

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Purpose To investigate, in a meta-analysis, the frequency of pulmonary embolism (PE) in patients with COVID-19 and whether D-dimer assessment may be useful to select patients for computed tomography pulmonary angiography (CTPA). Methods A systematic literature search was performed for original studies which reported the frequency of PE on CTPA in patients with COVID-19. The frequency of PE, the location of PE, and the standardized mean difference (SMD) of D-dimer levels between patients with and without PE were pooled by random effects models. Results Seventy-one studies were included. Pooled frequencies of PE in patients with COVID-19 at the emergency department (ED), general wards, and intensive care unit (ICU) were 17.9% (95% CI: 12.0–23.8%), 23.9% (95% CI: 15.2–32.7%), and 48.6% (95% CI: 41.0–56.1%), respectively. PE was more commonly located in peripheral than in main pulmonary arteries (pooled frequency of 65.3% [95% CI: 60.0–70.1%] vs. 32.9% [95% CI: 26.7–39.0%]; OR = 3.540 [95% CI: 2.308–5.431%]). Patients with PE had significantly higher D-dimer levels (pooled SMD of 1.096 [95% CI, 0.844–1.349]). D-dimer cutoff levels which have been used to identify patients with PE varied between 1000 and 4800 μg/L. Conclusion The frequency of PE in patients with COVID-19 is highest in the ICU, followed by general wards and the ED. PE in COVID-19 is more commonly located in peripheral than in central pulmonary arteries, which suggests local thrombosis to play a major role. D-dimer assessment may help to select patients with COVID-19 for CTPA, using D-dimer cutoff levels of at least 1000 μg/L. Key Points • The frequency of PE in patients with COVID-19 is highest in the ICU, followed by general wards and the ED. • PE in COVID-19 is more commonly located in peripheral than in central pulmonary arteries. • D-dimer levels are significantly higher in patients with COVID-19 who have PE. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-08003-8.

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“…In a prospective study of 156 non-ICU COVID-19 patients with D-dimer levels > 1000 ng/ml, compression ultrasound screening for asymptomatic DVT showed an incidence of 14.7% (only one proximal DVT) [7]; findings in line with another systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography in 84 consecutive non-ICU patients despite uniform pharmacological thromboprophylaxis (incidence of 11.9%; 2.4% proximal DVT). Again, high D-dimer levels (> 3000 µg/L) were indicative of the presence of asymptomatic VTE [8]. In a retrospective cohort study of 71 non-ICU treated COVID-19 patients on anticoagulant thromboprophylaxis, who underwent systematic low limb venous duplex ultrasonography at hospital discharge or earlier if DVT was clinically suspected, 16 patients developed VTE (22.5%) and 7 PE (10%) [9].…”

Section: On the General Ward (Non-icu)mentioning

confidence: 99%

Screening for venous thromboembolism in patients with COVID-19

Vandenbriele

Gorog

2021

J Thromb Thrombolysis

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Pulmonary thromboembolism and deep venous thrombosis occur frequently in hospitalised patients with COVID-19, the prevalence increases on the intensive care unit (ICU) and is very high in patients on extracorporeal membrane oxygenation (ECMO). We undertook a literature review to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. Outside of the ICU setting, D-dimer elevation on presentation or marked increase from baseline should alert the need for doppler ultrasound scan of the lower limbs. In the ICU setting, consideration should be given to routine screening with doppler ultrasound, given the high prevalence of thrombosis in this cohort despite standard anticoagulant thromboprophylaxis. However, absence of lower limb thrombosis on ultrasound does not exclude pulmonary venous thrombosis. Screening with CT pulmonary angiography (CTPA) is not justified in patients on the general wards, unless there are clinical features and/or marked elevations in markers of COVID-19-associated coagulopathy. However, the risk of pulmonary embolism or pulmonary thrombosis in ICU patients is very high, especially in patients on ECMO, where studies that employed routine screening for thrombosis with CT scanning have uncovered up to 100% incidence of pulmonary thrombosis despite standard anticoagulant thromboprophylaxis. Therefore, in patients at low bleeding risk and high clinical suspicion of venous thromboembolism, therapeutic anticoagulation should be considered even before screening, Our review highlights the need for increased vigilance for VTE, with a low threshold for doppler ultrasound and CTPA in high risk in-patient cohorts, where clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism.

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High rate of pulmonary thromboembolism in patients with SARS-CoV-2 pneumonia

Cited by 11 publications

References 5 publications

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Pulmonary embolism in patients with COVID-19 and value of D-dimer assessment: a meta-analysis

Screening for venous thromboembolism in patients with COVID-19

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