Pulmonary thromboembolism in hospitalised COVID-19 patients at moderate to high risk by Wells score: a report from Lombardy, Italy

Monfardini, Lorenzo; Morassi, Mauro; Botti, Paolo; Stellini, Roberto; Bettari, Luca; Pezzotti, Stefania; Alì, Marco; Monaco, Cristian Giuseppe; Magni, Veronica; Cozzi, Andrea; Schiaffino, Simone; Bnà, Claudio

doi:10.1259/bjr.20200407

Cited by 22 publications

(35 citation statements)

References 15 publications

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“…Similarly, among 34 COVID-19 patients who underwent CTPA, 26 had PE (76%; 20 males, median age 61 years, 77% with comorbidities). 48 Mortality was at 31% in this group. Importantly, 8 PE patients had been under thromboprophylaxis with low-molecular-weight heparin; 4 PE patients had DVT at ultrasound examination.…”

Section: Pulmonary Angiopathy/computed Tomography Findingsmentioning

confidence: 61%

COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management

Manolis¹,

Manolis

et al. 2020

J Cardiovasc Pharmacol Ther

110

100

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Coronavirus-2019 (COVID-19) predisposes patients to arterial and venous thrombosis commonly complicating the clinical course of hospitalized patients and attributed to the inflammatory state, endothelial dysfunction, platelet activation and blood stasis. This viral coagulopathy may occur despite thromboprophylaxis and raises mortality; the risk appears highest among critically ill inpatients monitored in the intensive care unit. The prevalence of venous thromboembolism in COVID-19 patients has been reported to reach ∼10-35%, while autopsies raise it to nearly 60%. The most common thrombotic complication is pulmonary embolism, which though may occur in the absence of a recognizable deep venous thrombosis and may be due to pulmonary arterial thrombosis rather than embolism, resulting in thrombotic occlusion of small- to mid-sized pulmonary arteries and subsequent infarction of lung parenchyma. This micro-thrombotic pattern seems more specific for COVID-19 and is associated with an intense immuno-inflammatory reaction that results in diffuse occlusive thrombotic micro-angiopathy with alveolar damage and vascular angiogenesis. Furthermore, thrombosis has also been observed in various arterial sites, including coronary, cerebral and peripheral arteries. Biomarkers related to coagulation, platelet activation and inflammation have been suggested as useful diagnostic and prognostic tools for COVID-19-associated coagulopathy; among them, D-dimer remains a key biomarker employed in clinical practice. Various medical societies have issued guidelines or consensus statements regarding thromboprophylaxis and treatment of these thrombotic complications specifically adapted to COVID-19 patients. All these issues are detailed in this review, data from meta-analyses and current guidelines are tabulated, while the relevant mechanisms of this virus-associated coagulopathy are pictorially illustrated.

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Section: Pulmonary Angiopathy/computed Tomography Findingsmentioning

confidence: 61%

COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management

Manolis¹,

Manolis

et al. 2020

J Cardiovasc Pharmacol Ther

110

100

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“… 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. Miró et al [ 67 ] Spain and France March 6–April 15 -320 -NR -NR PE suspected based on patient signs and symptoms NR NR Moll et al [ 69 ] USA March 7–April 13 -25 -NR -NR NR NR NR Monfardini et al [ 70 ] Italy March 1–March 31 -34 -NR -NR Sudden oxygen desaturation coupled with a moderate to high risk of PE according to the Wells score and D-dimer levels 8 patients (23.5%) Two experienced thoracic radiologist with 15 and 20 years of experience Mouhat et al [ 71 ] France March 15–April 16 -162 -Mean 65.57 years (± 13.00) -109 males Oxygen saturation measured by pulse oximetry ≤ 93% in room air, breathing rate of ≥ 30 breaths/minute or rapid clinical worsening 141 patients (87.0%) Two chest radiologists Mueller-Peltzer et al [ 72 ] Germany March 8–April 15 -16 -Mean 62.2 years (range 47–77) -10 males When likelihood of PE was considered high 4 patients (25%) Two radiologists with 6 and 13 years of experience in thoracic radiology O'Shea et al [ 73 ] USA March 17–April 6 -94 -NR -NR NR NR Radiologist with 7 years of experience in cardiovascular imaging Ooi et al [ 74 ] UK March 1–April 30 …”

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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“…Ventura-Díaz et al 20 Espallargas et al 25 Mueller-Peltzer et al 26 Ramadan et al 27 Mouhat et al 30 Alonso-Fernández et al 32 Monfardini et al 39 Freund et al 40 Chen et al 41 Whyte et al 43 Fauvel et al 45 Larsen et al 48 Bavaro et al 51 Mazzaccaro et al 53 Gervaise et al 54 Poyiadji et al 60 Bompard et al 62 BDL Overall (I 2 = 94.8%) patients with severe COVID-19. 68 It has been suggested that SARS-Cov-2 in severe forms of the disease induces an excessive inflammatory state via cytokine storm combined with endothelial injury and pulmonary vascular microthrombosis, which could considerably increase the risk for VTE, mainly PE.…”

Section: Table 1 (Continued)mentioning

confidence: 99%

Venous thromboembolism in COVID-19: A systematic review and meta-analysis

et al. 2021

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Severe coronavirus disease 2019 (COVID-19) is associated with increased risk of venous thromboembolism events (VTE). This study performed a systematic review in PubMed/EMBASE of studies reporting the prevalence of VTE in patients with COVID-19 who were totally screened/assessed for deep vein thrombosis (DVT) and/or for pulmonary embolism (PE). Among 47 candidate studies ( n = 6459; 33 in Europe), 17 studies ( n = 3973; weighted age 63.0 years, males 60%, intensive care unit (ICU) 16%) reported the prevalence of PE with a pooled estimate of 32% (95% CI: 25, 40%), and 32 studies ( n = 2552; weighted age 62.6 years, males 57%, ICU 49%) reported the prevalence of DVT with a pooled estimate of 27% (95% CI: 21, 34%). A total of 36 studies reported the use of at least prophylactic antithrombotic treatment in the majority of their patients. Meta-regression analysis showed that the prevalence of VTE was higher across studies with a higher percentage of ICU patients and higher study population mean D-dimer values, and lower in studies with mixed dosing of anticoagulation in ⩾ 50% of the population compared to studies with standard prophylactic dosing of anticoagulation in < 50% of the population. The pooled odds ratio for death in patients with COVID-19 and VTE versus those without VTE (17 studies, n = 2882) was 2.1 (95% CI: 1.2, 3.6). Hospitalized patients with severe COVID-19 are at high VTE risk despite prophylactic anticoagulation. Further research should investigate the individualized VTE risk of patients with COVID-19 and the optimal preventive antithrombotic therapy. PROSPERO Registration No.: CRD42020185543.

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Pulmonary thromboembolism in hospitalised COVID-19 patients at moderate to high risk by Wells score: a report from Lombardy, Italy

Cited by 22 publications

References 15 publications

COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management

COVID-19 Infection: Viral Macro- and Micro-Vascular Coagulopathy and Thromboembolism/Prophylactic and Therapeutic Management

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

Venous thromboembolism in COVID-19: A systematic review and meta-analysis

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