RESUMEN
COVID-19 is frequently associated with abnormalities on coagulation testing and a coagulopathy driven by inflammation, intravascular coagulation activation, and microvascular thrombosis. Elevated D-dimer is the most common finding and is a predictor of adverse outcomes including thrombosis, critical illness, and death. Although COVID-19-associated coagulopathy has some similarities to disseminated intravascular coagulation, the platelet count is usually preserved, coagulation times are usually normal or minimally prolonged, and thrombosis is more common than bleeding, at least in noncritically ill patients. Bleeding is uncommon but may be a significant problem in critically ill patients, including those who may develop a consumptive coagulopathy with frank disseminated intravascular coagulation and those on extracorporeal membrane oxygenation. Blood product support to correct coagulopathy is reserved for bleeding patients or those requiring invasive procedures. Current recommendations suggest that all hospitalized patients should receive at least a prophylactic dose of anticoagulation. Results from a multiplatform randomized clinical trial suggest that therapeutically dosed anticoagulation may improve outcomes, including the need for organ support and mortality in moderately ill patients but not in those requiring critical care. The results of ongoing trials evaluating the impact of different antithrombotic strategies (therapeutic agents and intensity) on COVID-19 outcomes are eagerly awaited and are expected to have important implications for patient management. We also discuss COVID-19 vaccine-associated cytopenias and bleeding as well as vaccine-induced thrombotic thrombocytopenia, in which thrombosis is associated with thrombocytopenia, elevated D-dimer, and, frequently, hypofibrinogenemia.
Asunto(s)
Coagulación Sanguínea , Vacunas contra la COVID-19/efectos adversos , COVID-19/complicaciones , Trombocitopenia/etiología , Trombosis/etiología , Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , COVID-19/sangre , COVID-19/prevención & control , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Persona de Mediana Edad , Trombocitopenia/sangre , Trombocitopenia/terapia , Trombofilia/sangre , Trombofilia/etiología , Trombofilia/terapia , Trombosis/sangre , Trombosis/terapiaRESUMEN
The COVID-19 pandemic has introduced a global public health threat unparalleled in our history. The most severe cases are marked by ARDS attributed to microvascular thrombosis. Hypercoagulability, resulting in a profoundly prothrombotic state, is a distinct feature of COVID-19 and is accentuated by a high incidence of fibrinolysis shutdown. The aims of this review were to describe the manifestations of fibrinolysis shutdown in COVID-19 and its associated outcomes, review the molecular mechanisms of dysregulated fibrinolysis associated with COVID-19, and discuss potential implications and therapeutic targets for patients with severe COVID-19.
Asunto(s)
COVID-19/complicaciones , Fibrinólisis , Trombofilia/etiología , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/terapia , Trastornos de la Coagulación Sanguínea/virología , COVID-19/sangre , Humanos , Trombofilia/terapia , Trombofilia/virologíaAsunto(s)
Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/complicaciones , COVID-19/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Trombofilia/etiología , COVID-19/diagnóstico , COVID-19/terapia , Humanos , Masculino , Persona de Mediana Edad , Trombofilia/diagnóstico , Trombofilia/terapiaAsunto(s)
COVID-19 , Electrocardiografía/métodos , Insuficiencia Respiratoria , Trombofilia , Adulto , COVID-19/complicaciones , COVID-19/fisiopatología , COVID-19/terapia , Deterioro Clínico , Angiografía por Tomografía Computarizada/métodos , Resultado Fatal , Femenino , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Humanos , Manejo de Atención al Paciente/métodos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Respiración Artificial/métodos , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , SARS-CoV-2/aislamiento & purificación , Trombofilia/sangre , Trombofilia/etiología , Trombofilia/fisiopatología , Trombofilia/terapia , Disfunción Ventricular/diagnóstico , Disfunción Ventricular/etiologíaRESUMEN
Emerging evidence has documented that multisystem organ failure in coronavirus disease 2019 (COVID-19) patients is strongly associated with various coagulopathies. Treatments for COVID-19-associated coagulopathy are still a clinical challenge. An advancement in the knowledge of mechanisms of the excessive or inappropriate activation of the complement cascade involved in the genesis of COVID-19-associated coagulopathy might be a fundamental approach for developing novel classes of anticoagulant drugs. In this context, there is emerging evidence indicating that C5a, a component of the complement system, and its receptors (C5aRs) play a critical role in the genesis of the COVID-19-associated hypercoagulable state. Thus, this review describes the mechanisms by which C5a/C5aR signaling participates in the cascade of events involved in the pathophysiology of COVID-19-associated coagulopathy. Furthermore, it highlights the current possibilities for the development of a novel therapeutic approach for COVID-19 patients that targets C5a/C5aRs signaling.
Asunto(s)
COVID-19/terapia , Complemento C5a/fisiología , Complemento C5a/uso terapéutico , Trombofilia/terapia , Animales , COVID-19/sangre , COVID-19/complicaciones , COVID-19/epidemiología , Activación de Complemento/fisiología , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Transducción de Señal , Trombofilia/epidemiología , Trombofilia/etiologíaRESUMEN
ABSTRACT: Patients with severe coronavirus disease-2019 (COVID-19) frequently have hypercoagulability caused by the immune response to the severe acute respiratory syndrome coronavirus-2 infection. The pathophysiology of COVID-19 associated hypercoagulability is not fully understood, but characteristic changes include: increased fibrinogen concentration, increased Factor VIII activity, increased circulating von Willebrand factor, and exhausted fibrinolysis. Anticoagulant therapy improves outcomes in mechanically ventilated patients with COVID-19 and viscoelastic coagulation testing offers an opportunity to tailor anticoagulant therapy based on an individual patient's coagulation status. In this narrative review, we summarize clinical manifestations of COVID-19, mechanisms, monitoring considerations, and anticoagulant therapy. We also review unique considerations for COVID-19 patients who are on extracorporeal membrane oxygenation.
Asunto(s)
COVID-19/diagnóstico , COVID-19/terapia , Trombofilia/diagnóstico , Trombofilia/terapia , Anticoagulantes/uso terapéutico , Pruebas de Coagulación Sanguínea , Viscosidad Sanguínea/fisiología , COVID-19/sangre , Terapia Combinada , Correlación de Datos , Endotelio Vascular/fisiopatología , Oxigenación por Membrana Extracorpórea , Factor VIII/fisiología , Fibrinógeno/fisiología , Fibrinólisis/efectos de los fármacos , Fibrinólisis/fisiología , Humanos , Monitoreo Fisiológico , Respiración Artificial , Tromboelastografía , Trombofilia/sangreRESUMEN
In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.
Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/fisiopatología , Neumonía Viral/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Células Epiteliales Alveolares/inmunología , Células Epiteliales Alveolares/patología , Animales , Betacoronavirus/inmunología , COVID-19 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Humanos , Inmunidad Innata , Inflamación/etiología , Inflamación/inmunología , Inflamación/fisiopatología , Inflamación/terapia , Activación de Macrófagos , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/patología , Activación Neutrófila , Pandemias , Activación Plaquetaria , Neumonía Viral/complicaciones , Neumonía Viral/inmunología , Neumonía Viral/terapia , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/terapia , SARS-CoV-2 , Trombofilia/etiología , Trombofilia/inmunología , Trombofilia/fisiopatología , Trombofilia/terapiaRESUMEN
COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.
Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/complicaciones , Pandemias , Neumonía Viral/complicaciones , Trombofilia/etiología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Anticoagulantes/uso terapéutico , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/fisiopatología , Arteriopatías Oclusivas/virología , COVID-19 , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Cateterismo de Swan-Ganz , Terapia Combinada , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/tratamiento farmacológico , Endotelio Vascular/fisiopatología , Endotelio Vascular/virología , Fibrinolíticos/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica , Inhibidores de Agregación Plaquetaria/uso terapéutico , Neumonía Viral/sangre , Neumonía Viral/tratamiento farmacológico , Embolia Pulmonar/etiología , Embolia Pulmonar/terapia , Embolia Pulmonar/virología , Síndrome de Dificultad Respiratoria/etiología , SARS-CoV-2 , Terapia Trombolítica/instrumentación , Terapia Trombolítica/métodos , Trombofilia/fisiopatología , Trombofilia/terapia , Trombosis de la Vena/etiología , Trombosis de la Vena/fisiopatología , Trombosis de la Vena/virología , Internalización del Virus/efectos de los fármacos , Tratamiento Farmacológico de COVID-19Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Terapia por Ejercicio , Neoplasias/sangre , Pandemias , Neumonía Viral , Embolia Pulmonar/prevención & control , Cuarentena , Autocuidado , Trombofilia/etiología , Tromboembolia Venosa/prevención & control , COVID-19 , Cuidadores , Atención Domiciliaria de Salud , Humanos , Neoplasias/complicaciones , Prescripciones , Embolia Pulmonar/etiología , SARS-CoV-2 , Trombofilia/terapia , Tromboembolia Venosa/etiologíaRESUMEN
This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Pandemias , Neumonía Viral/complicaciones , Guías de Práctica Clínica como Asunto , Trombofilia/terapia , Trombosis/prevención & control , Anticoagulantes/uso terapéutico , Biomarcadores , COVID-19 , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/sangre , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/etiología , Manejo de la Enfermedad , Endotelio Vascular/fisiopatología , Endotelio Vascular/virología , Medicina Basada en la Evidencia , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/prevención & control , Neumonía Viral/sangre , Venas Pulmonares , SARS-CoV-2 , Trombofilia/etiología , Tromboflebitis/etiología , Tromboflebitis/prevención & control , Trombosis/etiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlAsunto(s)
Infecciones por Coronavirus/epidemiología , Servicio de Urgencia en Hospital/organización & administración , Pandemias , Neumonía Viral/epidemiología , Enfermedades Vasculares/epidemiología , Anticoagulantes/uso terapéutico , COVID-19 , Comorbilidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/fisiopatología , Estudios Transversales , Procedimientos Quirúrgicos Electivos , Urgencias Médicas , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Heparina/uso terapéutico , Humanos , Italia/epidemiología , Neumonía Viral/complicaciones , Neumonía Viral/fisiopatología , Trombofilia/sangre , Trombofilia/etiología , Trombofilia/terapia , Ultrasonografía Doppler Dúplex , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/terapia , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Trombosis de la Vena/prevención & controlRESUMEN
The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment.
Asunto(s)
Infecciones por Coronavirus/complicaciones , Fibrinolíticos/uso terapéutico , Neumonía Viral/complicaciones , Trombofilia/prevención & control , Trombofilia/terapia , Trombosis/prevención & control , Trombosis/terapia , Algoritmos , Betacoronavirus , COVID-19 , Cardiología , Infecciones por Coronavirus/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Fallo Hepático/terapia , Pandemias , Tiempo de Tromboplastina Parcial , Recuento de Plaquetas , Neumonía Viral/sangre , Tiempo de Protrombina , Riesgo , SARS-CoV-2 , Resultado del TratamientoRESUMEN
Three leading infectious disease experts in China were invited to share their bedside observations in the management of COVID-19 patients. Professor Taisheng Li was sent to Wuhan to provide frontline medical care. He depicts the clinical course of SARS-CoV-2 infection. Furthermore, he observes the significant abnormality of coagulation function and proposes that the early intravenous immunoglobulin and low molecular weight heparin anticoagulation therapy are very important. Professor Hongzhou Lu, a leader in China to try various anti-viral drugs, expresses concern on the quality of the ongoing clinical trials as most trials are small in scale and repetitive in nature, and emphasizes the importance of the quick publication of clinical trial results. Regarding the traditional Chinese medicine, Professor Lu suggests to develop a creative evaluation system because of the complicated chemical compositions. Professor Wenhong Zhang is responsible for Shanghai's overall clinical management of the COVID-19 cases. He introduces the team approach to manage COVID-19 patients. For severe or critically ill patients, in addition to the respiratory supportive treatment, timely multiorgan evaluation and treatment is very crucial. The medical decisions and interventions are carefully tailored to the unique characteristics of each patient.