Coagulation disorders and thromboembolic disease in COVID-19: review of current evidence in search of a better approach.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an unprecedented global health problem, causing more than 20 million infections and more than 900,000 deaths (September 2020). The SARS-CoV-2 infection, known as COVID-19, has various clinical presentations, from asymptomatic or mild catarrhal processes to severe pneumonia that rapidly progresses to acute respiratory distress syndrome (ARDS) and multiple organ failure. In the last few months, much scientific literature has been devoted to descriptions of different aspects of the coagulation disorders and arterial and venous thrombotic complications associated with COVID-19, particularly venous thromboembolism (VTE). These studies have revealed that SARS-CoV-2 could lead to a prothrombotic state reflecting the high cumulative incidence of associated thrombotic events, particularly in patients admitted to intensive care units (ICUs). As regards the coagulopathy observed in association with SARS-CoV-2 infection, the mechanisms that activate coagulation have been hypothesized as being linked to immune responses, through the release of pro-inflammatory mediators that interact with platelets, stimulate the expression of tissue factor, induce an upregulation of plasminogen activator inhibitor-1, suppress the fibrinolytic system and lead to endothelial dysfunction, triggering thrombogenesis. D-dimer elevation has been recognized as a useful biomarker of poor prognosis, although the best cut-off point for predicting VTE in COVID-19 patients has still not been clarified. This review will try to update all the available scientific information on this important topic with enormous clinical and therapeutic implications.

[Thrombotic Risk and Covid-19: Review of Current Evidence for a Better Diagnostic and Therapeutic Approach]. / Riesgo trombótico y COVID-19: revisión de la evidencia actual para una mejor aproximación diagnóstica y terapéutica.

The new SARS-CoV-2 coronavirus has created an unprecedented global health problem, resulting in more than 250,000 confirmed deaths. The disease produced by this virus, called Covid-19, presents with variable clinical manifestations, from practically asymptomatic patients with catarrhal processes to severe pneumonias that rapidly evolve to acute respiratory distress syndrome (ARDS) and multiorgan failure. In recent weeks, papers have been published describing coagulation disorders and arterial and venous thrombotic complications in these patients, mainly among those admitted to intensive care units. The infection triggers an immune response, which causes different inflammatory mediators to be released into the blood. These include cytokines, which interact with platelets and different coagulation proteins, and promote thrombogenesis. One of the most widely studied coagulation markers in Covid-19 is D-dimer (DD), raised levels of which have prognostic implications, although the best cut-off point for the diagnosis of venous thromboembolism (VTE) in this population has not been clarified, nor has its usefulness in determining the intensity of thromboprophylaxis required in these patients. Until sufficiently robust information (preferably from well-designed clinical trials) is available, the recommendations of clinical practice guidelines for the prophylaxis, diagnosis and treatment of VTE should be followed in Covid-19 patients.

Incidence, risk factors, and thrombotic load of pulmonary embolism in patients hospitalized for COVID-19 infection.

OBJECTIVE: To determine the incidence, characteristics, and risk factors of pulmonary embolism (PE) among patients hospitalized for COVID-19. PATIENTS AND METHODS: We performed a prospective observational study of a randomly selected cohort of consecutive patients hospitalized for COVID-19 infection between March 8, 2020 through April 25, 2020. All eligible patients underwent a computed tomography pulmonary angiography independently of their PE clinical suspicion and were pre-screened for a baseline elevated D-dimer level. RESULTS: 119 patients were randomly selected from the 372 admitted to one tertiary hospital in Valencia (Spain) for COVID-19 infection during the period of study. Seventy-three patients fulfilled both the inclusion criteria and none of the exclusion criteria and were finally included in the study. Despite a high level of pharmacological thromboprophylaxis (89%), the incidence of PE was 35.6% (95% confidence interval [CI], 29.6 to 41.6%), mostly with a peripheral location and low thrombotic load (Qanadli score 18.5%). Multivariate analysis showed that heart rate (Hazard Ratio [HR], 1.04), room-air oxygen saturation (spO2) (HR, 0.87), D-dimer (HR, 1.02), and C-reactive protein (CRP) levels (HR, 1.01) at the time of admission were independent predictors of incident PE during hospitalization. A risk score was constructed with these four variables showing a high predictive value of incident PE (AUC-ROC: 0.86; 95% CI: 0.80 to 0.93). CONCLUSIONS: Our findings confirmed a high incidence of PE in hospitalized COVID-19 patients. Heart rate, spO2, D-dimer, and CRP levels at admission were associated with higher rates of PE during hospitalization.

Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55-74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84-91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3-15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6-4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1-13%) among patients in hospital wards and 19% (95% CI: 13-26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

Documento de Consenso de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) para el seguimiento clínico post-COVID-19

RESUMEN La infección por SARS-CoV-2 puede favorecer el desarrollo de diversas secuelas respiratorias, sobre todo en los pacientes que han sufrido una neumonía grave por COVID-19. Dado el elevado número de pacientes que sufrieron esta infección en un corto periodo de tiempo, se están llevando a cabo numerosas visitas de control post-COVID-19 sin que se haya establecido un protocolo de seguimiento clínico que aconseje sobre las pruebas complementarias a realizar y la frecuencia de las mismas. Este documento de consenso realizado por profesionales de distintas áreas de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR), pretende ayudar al profesional clínico a la identificación de las posibles complicaciones respiratorias que pueden aparecen durante los meses posteriores al cuadro agudo de la enfermedad y a protocolizar su seguimiento y las pruebas complementarias a realizar. Se sugieren las exploraciones e intervenciones a realizar en diversos momentos de la evolución post-COVID-19, con unos objetivos concretos. Por un lado, garantizar que los pacientes reciban un seguimiento clínico oportuno, con un cronograma preestablecido teniendo en cuenta la gravedad de la enfermedad y la probabilidad de secuelas a largo plazo;por otro lado, evitar sobrecargas del sistema sanitario llevando a cabo exploraciones y/o consultas en muchos casos innecesarias;por último, definir criterios para derivar a aquellos pacientes con determinadas secuelas específicas establecidas (enfermedad pulmonar intersticial, enfermedad vascular pulmonar o bronquiectasias) a las unidades monográficas correspondientes. ABSTRACT SARS-CoV-2 infection can cause a range of respiratory sequelae, especially in patients who have had severe Covid-19 pneumonia. Given the high number of patients who have developed this infection over a short period of time, numerous post-Covid-19 follow-up visits are being carried out, but no clinical follow-up protocol has been established to advise on the complementary tests to be performed and the frequency of these procedures. This consensus document was drawn up by professionals from different areas of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) in order to assist the clinician in identifying possible respiratory complications that may occur during the months following the acute disease, and to protocolize their follow-up and additional tests to be performed. It recommends examinations and interventions to be carried out at various stages in the post-Covid-19 period, and details the specific objectives of these procedures. Primarily, we aim to ensure that patients receive timely clinical follow-up, following a pre-established schedule that takes into account the severity of the disease and the likelihood of long-term sequelae. Another objective is to avoid overloading the health system by eschewing examinations and/or consultations that are, in many cases, unnecessary. Finally, we define criteria for referring patients with specific established sequelae (interstitial lung disease, pulmonary vascular disease, bronchiectasis) to the corresponding specialized units.