RESUMO
COVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ immunothrombosis in the pulmonary vascular tree. The incidence of thrombotic complications is dependent on setting (intensive care unit (ICU) versus general ward) and the threshold for performing diagnostic tests (screening versus diagnostic algorithms triggered by symptoms). Since these thrombotic complications are associated with in-hospital mortality, all current guidelines and consensus papers propose pharmacological thromboprophylaxis in all hospitalized patients with COVID-19. Several trials are ongoing to study the optimal intensity of anticoagulation for this purpose. As for the management of thrombotic complications, treatment regimens from non-COVID-19 guidelines can be adapted, with choice of anticoagulant drug class dependent on the situation. Parenteral anticoagulation is preferred for patients on ICUs or with impending clinical deterioration, while oral treatment can be started in stable patients. This review describes current knowledge on incidence and pathophysiology of COVID-19 associated VTE and provides an overview of guideline recommendations on thromboprophylaxis and treatment of established VTE in COVID-19 patients.
Assuntos
COVID-19/complicações , Quimioprevenção/métodos , Gerenciamento Clínico , Tromboembolia Venosa , COVID-19/sangue , Humanos , Incidência , Guias de Prática Clínica como Assunto , SARS-CoV-2 , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/fisiopatologia , Tromboembolia Venosa/terapiaRESUMO
INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.
Assuntos
COVID-19/complicações , Embolia Pulmonar/etiologia , Trombose/etiologia , Tromboembolia Venosa/etiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Estudos de Coortes , Estado Terminal/mortalidade , Feminino , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , SARS-CoV-2/isolamento & purificaçãoRESUMO
INTRODUCTION: We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. METHODS: We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. RESULTS: We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8). CONCLUSION: In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.
Assuntos
Arteriopatias Oclusivas/epidemiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/epidemiologia , Trombofilia/etiologia , Trombose Venosa/epidemiologia , Doença Aguda , Anticoagulantes/uso terapêutico , Arteriopatias Oclusivas/etiologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , COVID-19 , Estado Terminal , Embolia/epidemiologia , Embolia/etiologia , Feminino , Seguimentos , Hospitais de Ensino/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Países Baixos/epidemiologia , Pandemias , Embolia Pulmonar/etiologia , Trombofilia/tratamento farmacológico , Trombose Venosa/etiologiaRESUMO
INTRODUCTION: COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. METHODS: We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. RESULTS: We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. CONCLUSION: The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.