Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism.

BACKGROUND: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. METHODS: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. RESULTS: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. CONCLUSIONS: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".

A Prospective Study Evaluating Cumulative Incidence and a Specific Prediction Rule in Pulmonary Embolism in COVID-19.

Rationale: Abnormal values of hypercoagulability biomarkers, such as D-dimer, have been described in Coronavirus Disease 2019 (COVID-19), which has also been associated with disease severity and in-hospital mortality. COVID-19 patients with pneumonia are at greater risk of pulmonary embolism (PE). However, the real incidence of PE is not yet clear, since studies have been limited in size, mostly retrospective, and PE diagnostic procedures were only performed when PE was clinically suspected. Objectives: (1) To determine the incidence, clinical, radiological, and biological characteristics, and clinical outcomes of PE among patients hospitalized for COVID-19 pneumonia with D-dimer > 1,000 ng/mL. (2) To develop a prognostic model to predict PE in these patients. Methods: Single-center prospective cohort study. Consecutive confirmed cases of COVID-19 pneumonia with D-dimer > 1,000 ng/mL underwent computed tomography pulmonary angiography (CTPA). Demographic and laboratory data, comorbidities, CTPA scores, treatments administered, and clinical outcomes were analyzed and compared between patients with and without PE. A risk score was constructed from all these variables. Results: Between 6 April 2020 and 2 February 2021, 179 consecutive patients were included. The overall incidence of PE was 39.7% (71 patients) (CI 95%, 32-47%). In patients with PE, emboli were located mainly in segmental/subsegmental arteries (67%). Patients with PE did not differ from the non-PE group in sex, age, or risk factors for thromboembolic disease. Higher urea, D-Dimer, D-dimer-to-ferritin and D-dimer-to-lactate dehydrogenase (LDH) ratios, platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR) values were found in patients with PE when compared to patients with non-PE. Besides, lymphocyte counts turned out to be lower in patients with PE. A score for PE prediction was constructed with excellent overall performance [area under the ROC curve-receiver operating characteristic (AUC-ROC) 0.81 (95% CI: 0.73-0.89)]. The PATCOM score stands for Pulmonary Artery Thrombosis in COVID-19 Mallorca and includes platelet count, PDW, urea concentration, and D-dimer-to-ferritin ratio. Conclusion: COVID-19 patients with pneumonia and D-dimer values > 1,000 ng/mL were presented with a very high incidence of PE, regardless of clinical suspicion. Significant differences in urea, D-dimer, PDW, NLR, and lymphocyte count were found between patients with PE and non-PE. The PATCOM score is presented in this study as a promising PE prediction rule, although validation in further studies is required.

Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile. D-dimer elevation is particularly frequent, and values higher than 1µg/mL have been associated with disease severity and in-hospital mortality. Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected. MATERIAL AND METHODS: Single-center prospective cohort study. Between April 6th and April 17th 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 µg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE. Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE. RESULTS: Thirty consecutive patients (11 women) were included. PE was diagnosed in 15 patients (50%). In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%). Patients with PE were significantly older (median age 67.0 (IQR 63.0-73.0) vs. 57.0 (IQR 48.0-69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group. D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients. D-dimer values correlated with the radiologic magnitude of PE (p<0.001). CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 µg/mL presented a high prevalence of PE, regardless of clinical suspicion. We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found.

Obstructive sleep apnea is associated with worse clinical-radiological risk scores of pulmonary embolism.

Obstructive sleep apnea is a risk factor for pulmonary embolism, although its association with pulmonary embolism severity is unknown. Our objective was to study if obstructive sleep apnea is associated with worse pulmonary embolism severity scores and greater extent of arterial obstruction. In consecutive pulmonary embolism patients, we performed respiratory polygraphy and recorded sleep characteristics, classical risk factors for pulmonary embolism and physical activity 6-12 months after the pulmonary embolism episode. Simplified Geneva Prognostic Score and Pulmonary Embolism Severity Index were calculated at the time of the pulmonary embolism diagnosis. The Pulmonary Artery Obstruction Index and the right ventricle to left ventricle diameter ratio were measured by computed tomography pulmonary angiography. We included 120 patients, of whom 45.8% had moderate-severe obstructive sleep apnea (apnea-hypopnea index > 15 hr-1 ). There was a larger proportion of moderate-severe obstructive sleep apnea patients in the third and fourth Pulmonary Artery Obstruction Index quartiles and in the III-V Pulmonary Embolism Severity Index levels compared with apnea-hypopnea index < 15 hr-1 group. However, no differences were found between the proportion of patients with or without moderate-severe obstructive sleep apnea in their stratification by simplified Geneva Prognostic Score. The mean adjusted values of the simplified Geneva Prognostic Score, Pulmonary Embolism Severity Index and Pulmonary Artery Obstruction Index scores were higher in the apnea-hypopnea index > 15 hr-1 group (p < .05). Multiple linear regression analysis identified apnea-hypopnea index as the only independent factor related to Pulmonary Artery Obstruction Index and Pulmonary Embolism Severity Index, whereas desaturation index was associated with simplified Geneva Prognostic Score. Patients with pulmonary embolism and moderate-severe obstructive sleep apnea had greater pulmonary artery obstruction as well as more pulmonary embolism severity, assessed by both the simplified Geneva Prognostic Score and the Pulmonary Embolism Severity Index, compared with patients with apnea-hypopnea index ≤ 15 hr-1 . Moreover, these prognostic indices were independently related to sleep parameters.