Acute pulmonary embolism in times of SARS-CoV-2: Diagnostic and therapeutic management / Tromboembolismo pulmonar agudo en tiempos de SARS-CoV-2: diagnóstico y tratamiento

There is a clear association between novel coronavirus 2 infection and the diagnosis of venous thromboembolic disease, as a cosequence of the development of a systemic inflammatory response syndrome due to the activation of the coagulation cascade. It occurs in 90% of patients with severe forms of the infection, evidencing the presence of pulmonary endovascular micro and macro thrombosis. This suggests a possible clinical benefit of thromboprophylaxis according to the patient's clinical risk. The suspicion of venous thromboembolic disease in the context of this pandemic represents a diagnostic challenge due to the co-existence of similarities between both conditions in several different aspects. It should be noted that the diagnosis of acute pulmonary embolism does not exclude the possibility of simultaneous viral infection. The evaluation of patients with suspected acute pulmonary embolism in the context of the pandemic should be optimized in order to implement a rapid diagnosis and treatment to reduce the associated morbidity and mortality. This will help reducing infectious risk for health-care professionals and other patients.

Existe una clara relación entre la infección por el nuevo coronavirus 2 y el diagnóstico de enfermedad tromboembólica venosa, como consecuencia del desarrollo de un síndrome de respuesta inflamatoria sistémica debido a la activación de la cascada de la coagulación. Se presenta en el 90% de los pacientes con formas graves de la infección, lo que revela la presencia de microtrombosis y macrotrombosis intravascular pulmonar. Esto sugiere un posible beneficio clínico de la aplicación de una tromboprofilaxis adecuada al riesgo clínico de cada paciente. Asimismo, la sospecha de enfermedad tromboembólica venosa en el contexto de esta pandemia representa un reto diagnóstico debido a la existencia de similitudes entre ambas alteraciones en varios aspectos. Debe tenerse en cuenta que el diagnóstico de tromboembolismo pulmonar agudo no excluye la posibilidad de infección viral. La valoración de pacientes con sospecha de tromboembolismo pulmonar agudo en el contexto de la pandemia debe ser eficaz para establecer un diagnóstico y tratamiento con rapidez, a fin de reducir la morbilidad y mortalidad adjuntas, sin que ello eleve el riesgo de infección para los profesionales de la salud y otros pacientes.

Isolated pulmonary embolism - a specific clinical entity?

Pulmonary embolism in classical meaning is a complication of deep vein thrombosis (usually in the leg veins), developing after a part of the thrombus dislodged and got wedged in pulmonary arteries. However, in half of the patients with pulmonary embolism, deep vein thrombosis is not found. One potential explanation is a different, less common location of the thrombus or previous complete embolization of the whole thrombotic mass. Another possibility is pulmonary artery thrombosis in situ, which is a specific clinical entity associated with some typical risk factors. It develops in the place of vascular injury, as a consequence of hypoxia, inflammatory changes, endothelial dysfunction and injury. Pulmonary artery thrombosis in situ can be a complication after lung resection, radiation therapy, chest trauma, in the patients with Behçet´s disease, sickle cell anemia, chronic obstructive pulmonary disease, tuberculosis or covid pneumonia. Pulmonary artery thrombosis in situ may differ from classical pulmonary embolism in prognosis as well as in therapeutic approach.

Impact of COVID-19 Infection on the Clinical Outcomes of Pulmonary Embolism Hospitalizations : A Nationwide Analysis.

There is an increased risk of venous thromboembolism among patients with COVID-19 infection, with the risk being higher among those needing the intensive level of care. Existing data is, however, limited regarding the outcomes of patients admitted with concurrent COVID-19 infection and pulmonary embolism (PE). All acute PE admissions were identified from the National Inpatient Sample database during 2020 using ICD-10 codes. Patients were subsequently classified into those with and without COVID-19 infection. The primary outcome of interest was in-hospital mortality. Using multivariate logistic regression, the predictors of mortality were assessed for patients with concurrent acute PE and COVID-19. The database query generated 278,840 adult patients with a primary diagnosis of PE. Of these, 4580 patients had concurrent PE and COVID-19 infection. The concurrent PE and COVID-19 infection group had a higher proportion of Black-American and Hispanic patients, and those living in the zip codes associated with the lowest annualized income compared to the PE alone group. Furthermore, patients in the concurrent PE and COVID-19 infection group had an increased risk of in-hospital mortality (adjusted odds ratio [aOR]:1.62; 95% CI: 1.17-2.24; P = 0.004), septic shock (aOR: 1.66; 95% CI 1.10-2.52; P = 0.016), respiratory failure (aOR: 1.78; 95% CI 1.53-2.06; P = 0.001), and a longer hospital stay [5.5 days vs 4.59 days; P = 0.001). Concurrent COVID-19 and PE admissions is associated with an increased in-hospital mortality, risk of septic shock and respiratory failure, and a longer length of hospital stay.

COVID-19 and Blood Clots: A Report of Massive Pulmonary Embolism in COVID-19 Patient Supported on Veno-Venous ECMO and the Utility of Thrombolysis.

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our hospital. She was in profound shock requiring multiple vasopressors for hemodynamic support with worsening clinical status on arrival. On bedside echocardiography, she was found to have a massive pulmonary embolism with clot-in-transit visualized in the right atrium and right ventricular outflow tract. After a multidisciplinary discussion, systemic thrombolytic therapy was administered. The patient's hemodynamics improved and vasopressors were discontinued. This case illustrates the utility of bedside echocardiography in shock determination, the need for continued vigilance in the systematic evaluation of unstable patients in the intensive care unit, and the use of systemic thrombolytics during V-V ECMO in a novel disease process with evolving understanding.

[Home treatment of low-risk pulmonary embolism patients : Efficacy and safety of an outpatient program including the general practitioner]. / Prise en charge ambulatoire des embolies pulmonaires à risque faible ; expérience d'une filière centrée sur le lien ville-hôpital.

AIM: Outpatient treatment (OT) of patients with low-risk pulmonary embolisms (PE) is recommended. A multidisciplinary OT program including the general practitioner (GP) has been implemented at Versailles hospital in 2019. The objectives of the study were to assess the feasibility, safety and acceptability of the program. MATERIAL AND METHODS: The feasibility of, and the inclusion criteria for OT were defined from a retrospective cohort study of PE patients carried out in 2018. In the prospective study, consecutive patients consulting in the emergency department between 2019 and 2021 with confirmed PE were eligible for OT if they had sPESI and HESTIA scores equal to 0, normal troponin and NT-pro-BNP levels, and no right ventricular dilation on imaging. PEs associated with COVID were excluded. The OT program included 4 appointments within 3 months, including 2 with the GP. Events (death, recurrence of PE or venous thromboembolism, bleeding, rehospitalisation) were collected at 3-month follow-up. RESULTS: In the retrospective study, 19% of the 138 PE patients seen in the emergency department were eligible for OT. No complication occurred at Day 90. In the prospective study, 313 consecutive patients with confirmed PE in the emergency department were included, 66 (21%) were eligible for OT. Overall, 43 patients (14%) received OT (39 eligible) and 27 patients eligible for OT were hospitalised (92% because of pulmonary infarction). At 3-month follow-up, there were no death, no recurrence of thromboembolism, and one patient has been early hospitalised for COVID; 3 female patients treated with rivaroxaban had minor bleeding (heavy menstrual bleeding). The satisfaction rate of general practitioner was 95%. CONCLUSIONS: This study confirms the feasibility and safety of our OT program for low-risk EP patients, centered on the general practitioner. It reduces the time spent in the emergency department, reduces hospitalisations and strengthens the city-hospital link for care.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation on screening for chronic thromboembolic pulmonary hypertension patients after acute pulmonary embolism: Update.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (APE). Both pharmacological and invasive treatments for CTEPH are available in Poland, and awareness of the disease among physicians is growing. It has been suggested that the COVID-19 pandemic may increase the incidence of CTEPH and facilitate disease detection during more advanced stages of the illness. Thus, the Polish Cardiac Society's Working Group on Pulmonary Circulation, in cooperation with independent experts in this field, launched the updated statement on the algorithm to guide a CTEPH diagnosis in patients with previous APE. CTEPH should be suspected in individuals after APE with dyspnea, despite at least 3 months of effective anticoagulation, particularly when specific risk factors are present. Echocardiography is the main screening tool for CTEPH. A diagnostic workup of patients with significant clinical suspicion of CTEPH and right ventricular overload evident on echocardiography should be performed in reference centers. Pulmonary scintigraphy is a safe and highly sensitive screening test for CTEPH. Computed tomography pulmonary angiography with precise detection of thromboembolic residues in the pulmonary circulation is important for the planning of a pulmonary thromboendarterectomy. Right heart catheterization definitively confirms the presence of pulmonary hypertension and direct pulmonary angiography allows for the identification of lesions suitable for thromboendarterectomy or balloon pulmonary angioplasty. In this document, we propose a diagnostic algorithm for patients with suspected CTEPH. With an individualized and sequential diagnostic strategy, each patient can be provided with suitable and tailored therapy provided by a dedicated CTEPH Heart Team.

Venous Thrombosis and SARS-CoV-2.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is associated with high risk of venous and arterial thrombosis. Thrombotic complications, especially pulmonary embolism, lead to increased all-cause mortality in both intensive care unit and noncritically ill patients. Damage and activation of vascular endothelium, platelet activation, followed by thrombotic and fibrinolytic imbalance as well as hypercoagulability are the key pathomechanisms in immunothrombosis leading to a significant increase in thromboembolism in coronavirus disease 2019 (COVID-19) compared with other acute illnesses. In this review article, we discuss the incidence and prognosis, diagnosis, prevention, and treatment of venous thromboembolism in patients with COVID-19 disease, based on clinical experience and research available to date.

Impact of COVID-19 and lockdowns on pulmonary embolism in hospitalized patients in France: a nationwide study.

BACKGROUND: This study assessed the impact of the COVID-19 epidemic on overall hospitalizations for pulmonary embolism (PE) in France in comparison with previous years, and by COVID-19 and non-COVID-19 status. METHODS: Hospitalization data (2017-2020) were extracted from the French National Discharge database (all public and private hospitals). We included all patients older than 18 years hospitalized during the 3 years and extracted PE status and COVID-19 status (from March 2020). Age, sex and risk factors for PE (such as obesity, cancer) were identified. We also extracted transfer to an intensive care unit (ICU) and hospital death. The number of PE and the frequency of death in patients in 2019 and 2020 were described by month and by COVID-19 status. Logistic regressions were performed to identify the role of COVID-19 among other risk factors for PE in hospitalized patients. RESULTS: The overall number of patients hospitalized with PE increased by about 16% in 2020 compared with 2019, and mortality also increased to 10.3% (+ 1.2%). These increases were mostly linked to COVID-19 waves, which were associated with PE hospitalization in COVID-19 patients (PE frequency was 3.7%; 2.8% in non-ICU and 8.8% in ICU). The final PE odds ratio for COVID-19 hospitalized patients was 4 compared with other hospitalized patients in 2020. The analyses of PE in non-COVID-19 patients showed a 2.7% increase in 2020 compared with the previous three years. CONCLUSION: In 2020, the overall number of patients hospitalized with PE in France increased compared to the previous three years despite a considerable decrease in scheduled hospitalizations. Nevertheless, proactive public policy focused on the prevention of PE in all patients should be encouraged.

Venous Thromboembolism in Hospitalized COVID-19 Patients Treated in a Single Academic Center in Mexico: A Case Series Study.

BACKGROUND: The increasing prevalence of venous thromboembolism (VTE) among patients with coronavirus disease 2019 (COVID-19) is a matter of concern as it contributes significantly to patients' morbidity and mortality. Data regarding the optimal anticoagulation regimen for VTE prevention and treatment remain scarce. This study describes the characteristics, treatment, and outcomes of COVID-19 patients with VTE treated in a single academic center in Mexico. METHODS: We conducted a retrospective study of all patients with a positive PCR test for SARS-CoV-2 hospitalized in a single academic center in Monterrey, Mexico, between March 2020 and February 2021, with a radiologically confirmed VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE). Informed consent was obtained from each patient before reviewing their medical records. RESULTS: Of the 2000 COVID-19 hospitalized patients, 36 (1.8%) developed VTE and were included in the analysis. The median age was 60 years (range 32-88 years), and up to 78% (n = 28) were males. Most patients (n = 34, 94%) had an underlying comorbidity and 47% (n = 17) had a BMI ≥ 30 kg/m2. In most cases (n=28, 78%), VTE presented as a PE, whereas the remaining 22% (n = 8) had a DVT. The median time between hospital admission and VTE was 8 days (range 0-33 days). Regarding the thromboprophylaxis regimen, 35/36 patients received low molecular weight heparin enoxaparin on admission, most commonly at a dose of 60 mg daily (n = 19, 53%). Other complications presented were superinfection (n = 19, 53%), acute kidney injury (n = 11, 31%), and septic shock (n = 5, 14%). A total of 69% of patients (n = 25) required intensive care unit admission, and patients' overall mortality was 55.6%. CONCLUSION: VTE remains a significant cause of increased morbidity and mortality among patients with COVID-19. The strikingly high mortality among patients with VTE highlights the need for further investigation regarding the best preventive, diagnostic, and treatment approaches.

Cardiopulmonary resuscitation in special circumstances.

Cardiopulmonary resuscitation prioritises treatment for cardiac arrests from a primary cardiac cause, which make up the majority of treated cardiac arrests. Early chest compressions and, when indicated, a defibrillation shock from a bystander give the best chance of survival with a good neurological status. Cardiac arrest can also be caused by special circumstances, such as asphyxia, trauma, pulmonary embolism, accidental hypothermia, anaphylaxis, or COVID-19, and during pregnancy or perioperatively. Cardiac arrests in these circumstances represent an increasing proportion of all treated cardiac arrests, often have a preventable cause, and require additional interventions to correct a reversible cause during resuscitation. The evidence for treating these conditions is mostly of low or very low certainty and further studies are needed. Irrespective of the cause, treatments for cardiac arrest are time sensitive and most effective when given early-every minute counts.

Extensive deep vein thrombosis and pulmonary embolism as a unique clinical manifestation of COVID-19 in a young healthy patient.

BACKGROUND/OBJECTIVE: Deep vein thrombosis and pulmonary embolism have been described as complications in previously diagnosed COVID-19 patients, especially in those admitted in critical ill units, but, to our knowledge, there is no report of venous thromboembolism in an otherwise asymptomatic COVID-19 patient. METHODS: We report the case of a 22-year-old female, healthy patient with pulmonary embolism (Pulmonary Embolism Severity Index Score 22 points, low risk) and extensive proximal deep vein thrombosis as a unique clinical manifestation of the new coronavirus disease. RESULTS: The patient had no risk factors and no familial history of venous thromboembolism. All thrombophilia markers were negative. The patient was treated as first by an independent vascular team, performing vena cava filter placement and open thrombectomy. Her symptoms worsened, and after 3 weeks, she underwent US-enhanced thrombolysis and mechanical thrombectomy. She was isolated for 10 days and did not develop any other clinical manifestation of COVID-19 disease. During follow-up, she remained asymptomatic and complete patency of the venous system was achieved. Full oral anticoagulation was conducted for 6 months. CONCLUSION: COVID-19 appears to be a multi-symptomatic disease, and venous thromboembolism without any other previous described COVID-19 symptom could be considered one of its diverse clinical presentations and RT-PCR for SARS-CoV-2 tests emerge to be mandatory in patients with otherwise unexpected venous thrombosis.

Mechanical Thrombectomy in Pulmonary Embolism Associated with COVID-19: A "Clotography" Gallery.

Venous thromboembolism from a "thrombotic storm"-like syndrome is a major cause of morbidity and mortality in patients with active or "recovered" COVID-19. Patients should be risk-stratified, optimally by a pulmonary embolism (PE) response team (PERT), and considered for escalation of care if found with intermediate or high-risk PE. We present a series of patients with COVID-19-associated PE and thrombotic storm with D-dimer >10 000 ng/mL who underwent successful mechanical thrombectomy for intermediate to high-risk PE. All patients had immediate improvement in hemodynamics and large amounts of thrombi were retrieved.

Mortality and risk factors associated with pulmonary embolism in coronavirus disease 2019 patients: a systematic review and meta-analysis.

To determine, in patients with coronavirus disease 2019 (COVID-19) infection, the associations of pulmonary embolism (PE) with mortality and risk factors for PE as well as the therapeutic benefit of anticoagulant prophylaxis. Embase, PubMed, Cochrane controlled trials register, and Web of Science databases were searched from inception to October 10, 2020. We included all published trials on PE in patients diagnosed with COVID-19 with eligibility of the trials assessed following the PRISMA guidelines. Sixteen clinical trials with 5826 patients were eligible. There were significant associations of PE with the male gender [odd ratio (OR) = 1.59, 95% CI 1.28-1.97], mechanical ventilation (OR = 3.71, 95% CI 2.57-5.36), intensive care unit admission (OR = 2.99, 95% CI 2.11-4.23), circulating D-dimer [mean difference (MD) = 5.04 µg/mL, 95% CI 3.67-6.42) and CRP (MD = 1.97 mg/dL, 95% CI 0.58- 3.35) concentrations without significant correlation between PE and mortality (OR = 1.31, 95% CI 0.82-2.08) as well as other parameters or comorbidities. After omitting one trial with strict patient selection criteria for anticoagulant prophylaxis, significant prophylactic benefit was noted (OR = 0.31, 95% CI 0.1-0.91). Our findings identified the risk factors associated with PE in COVID-19 patients and supported the therapeutic benefit of anticoagulant prophylaxis against PE in this patient population.

Percutaneous Thrombus Removal in COVID-19-Infected Patient with Pulmonary Embolism.

We present a case describing the use of the AngioVac system (AngioDynamics, Inc.) and SENTINEL™ cerebral protection system (SCPS; Boston Scientific) in a patient with COVID-19 who initially presented with a large deep-vein thrombosis of the left lower extremity, complicated by a pulmonary embolism. Although he initially improved with systemic alteplase, he later developed a second large clot diagnosed in transit in the right atrium. Within 12 hours from initial thrombolysis, this large clot wedged across an incidental patent foramen ovale (PFO), the atrial septum, and the cavotricuspid annulus. We emergently performed a percutaneous clot extraction with preemptive placement of the SCPS in anticipation of cardioembolic phenomenon. A large (> 10 cm) clot was extracted without complication, and the patient was discharged home. The combined use of SCPS and AngioVac in this case suggests a potential role for percutaneous treatment of severe and consequential thromboembolic disease, especially in patients with a PFO, and may be considered as an alternative and less-invasive option in patients with COVID-19. While cerebral embolic protection devices are approved for and widely used in transcatheter aortic valve replacement procedures, there is a theoretical benefit for use in percutaneous thrombolectomies as well.

Impact and role of pulmonary embolism response teams in venous thromboembolism associated with COVID-19.

Venous thromboembolism associated with COVID-19, particularly acute pulmonary embolism, may represent a challenging and complex clinical scenario. The benefits of having a multidisciplinary pulmonary embolism response team (PERT) can be important during such a pandemic. The aim of PERT in the care of such patients is to provide fast, appropriate, multidisciplinary, team-based approach, with the common goal to tailor the best therapeutic decision making, prioritizing always optimal patient care, especially given lack of evidence-based clinical practice guidelines in the setting of COVID-19, which potentially confers a significant prothrombotic state. Herein, we would like to briefly emphasize the importance and potential critical role of PERT in the care of patients in which these two devastating illnesses are present together.