Pulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades,... Show morePulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades, diagnosing PE is still a difficult process due to the non-specific symptoms, which can frequently overlap with symptoms of other cardiopulmonary diseases. Currently recommended diagnostic strategies for suspected acute PE consist of standardized assessment of the clinical pre-test probability (CPTP) using validated clinical decision rules (CDRs) and D-dimer testing. PE is considered safely ruled out in patients with a non-high CPTP and a normal D-dimer test. Imaging tests as computed tomography pulmonary angiography (CTPA) are required in the case of a high CPTP and/or abnormal D-dimer test to confirm the diagnosis. The first part of this thesis describes the challenges of diagnosing PE in general and in specific clinically relevant patient subgroups. Moreover, this part evaluates the diagnostic performance of non-invasive diagnostic strategies for suspected PE in specific relevant patient subgroups. The second part of this thesis focuses on venous thrombotic complications in hospitalized patients with COVID-19. Show less
Hajjar, L.A.; Ancona, M.B.; Kalil, R.; Tresoldi, M.; Caldas, J.G.; Monti, G.; ... ; Montorfano, M. 2023
Background Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been... Show moreBackground Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome.Methods The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients.Results A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 +/- 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 +/- 4.6 mm(2), with stenosis of 60.9 +/- 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 +/- 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 & PLUSMN; 2.6, and the mean thrombus-containing lesion length was 14.1 +/- 13.9 mm. No peri-procedural complications occurred in any of the 13 patients.Conclusion OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Show less
Background Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be... Show moreBackground Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19. Methods Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible. Results From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria. Conclusions Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures. Show less
Venous thromboembolism (VTE), in particular acute pulmonary embolism (PE), has been shown to be a frequent and potentially fatal complication of coronavirus disease 2019 (COVID-19). In response to... Show moreVenous thromboembolism (VTE), in particular acute pulmonary embolism (PE), has been shown to be a frequent and potentially fatal complication of coronavirus disease 2019 (COVID-19). In response to the observed thrombotic complications, a large number of studies has been devoted to the understanding and management of COVID-19-associated coagulopathy. Notably, only a limited number of mostly retrospective studies has focused on the optimal diagnostic strategy for suspected PE in COVID-19 patients. As in other special populations, the accuracy of diagnostic algorithms for PE-exclusion has been debated in this specific patient subgroup as the specificity of D-dimer assays and clinical decision rules (CDRs) may be lower than normal. From this viewpoint, we discuss the current state-of-the-art diagnostic algorithms for acute PE with a focus on patients with COVID-19 in the perspective of other special patient populations. Furthermore, we summarize current knowledge regarding the natural history of PE resolution with anticoagulant treatment in patients with COVID-19. Show less
Accumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients... Show moreAccumulating studies on COVID-19 patients report high incidences of thrombotic complications, but guidance on the best diagnostic approach for suspected pulmonary embolism (PE) in COVID-19 patients is lacking. Diagnosing PE in these patients is challenging as signs and symptoms of PE and COVID-19 show wide overlap, D-dimer levels are often elevated in the absence of thrombosis and computed tomography pulmonary angiography (CTPA) may be unfeasible in the case of severe renal impairment and/or hemodynamic instability. This narrative review discusses available literature and guidelines on current diagnostic algorithms for suspected PE in special patient populations, in particular COVID-19. A special focus is on reviewing the literature aimed at identifying symptoms with a high suspicion for PE and on the diagnostic performance of diagnostic algorithms for suspected PE in the setting of COVID-19. Based on available literature, the index of suspicion for PE should be high in the case of unexplained abrupt worsening of respiratory status, typical symptoms of deep-vein thrombosis and/or acute unexplained right ventricular dysfunction. Despite the lack of prospective diagnostic management studies, we propose to adhere to current diagnostic algorithms applying assessment of pretest probability and D-dimer testing as available evidence suggests that these might be considered safe. Preferably, algorithms using adjusted D-dimer thresholds are recommended as it likely improves the yield of the clinical decision rule/D-dimer combination. Show less
