RESUMEN
Post-discharge thromboprophylaxis in patients admitted with COVID-19 remains controversial. We aimed to determine the impact of thromboprophylaxis on hospital acquired thrombosis (HAT) in patients (≥18 years) discharged following admission for COVID-19 in an observational study across 26 NHS Trusts in the UK (01.04.2020-31.12.2021). Overall, 8895 patients were included to the study: 971 patients were discharged with thromboprophylaxis and propensity score matched (PSM) with a desired ratio of 1:1, from patients discharged without thromboprophylaxis. Patients with heparin induced thrombocytopenia, major bleeding during admission and pregnant women were excluded. As expected from 1:1 PSM, no difference was observed in parameters between the two groups, including duration of hospital stay, except the thromboprophylaxis group had a significantly higher proportion who had received therapeutic dose anticoagulation during admission. There were no differences in the laboratory parameters especially D-dimers between the two groups at admission or discharge. Median duration of thromboprophylaxis following discharge from hospital was 4 weeks (1-8 weeks). No difference was found in HAT in patients discharged with TP versus no TP (1.3% vs. 0.92%, p = 0.52). Increasing age and smoking significantly increased the risk of HAT. Many patients in both cohorts had raised D-dimer at discharge but D-dimer was not associated with increased risk of HAT.
RESUMEN
OBJECTIVE: To establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) compared with a propensity-matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK. METHODS: This is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a predesigned standardized case record form. Adult patients (≥18 years) admitted between 1 April 2020 and 31 July 2020 were included. RESULTS: Overall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with SLE, RA or aPL syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia [240 (60.91%) vs 206 (52.28%), P = 0.015], elevated LDH [150 (38.08%) vs 43 (10.92%), P < 0.001] and raised creatinine [122 (30.96%) vs 86 (21.83%), P = 0.01], respectively. A significantly higher proportion of patients with severe rheumatologic AD had elevated CRP [77 (96.25%) vs 70 (87.5%), P = 0.044] and LDH [20 (25%) vs 6 (7.5%), P = 0.021]. Patients with severe rheumatologic AD had significantly higher mortality [32/80 (40%)] compared with propensity matched cohort of patients without AD [20/80 (25%), P = 0.043]. However, there was no difference in 180-day mortality between propensity-matched cohorts of patients with or without AD in general (P = 0.47). CONCLUSIONS: Patients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and elevated LDH were more frequent in patients with any AD while elevated CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19.
Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , COVID-19 , Adulto , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Reino Unido/epidemiologíaRESUMEN
Bleeding and thrombosis are major complications in patients supported with extracorporeal membrane oxygenation (ECMO). In this multicentre observational study of 152 consecutive patients (≥18 years) with severe COVID-19 supported by veno-venous (VV) ECMO in four UK commissioned centres during the first wave of the COVID-19 pandemic (1 March to 31 May 2020), we assessed the incidence of major bleeding and thrombosis and their association with 180-day mortality. Median age (range) was 47 years (23-65) and 75% were male. Overall, the 180-day survival was 70·4% (107/152). The rate of major bleeding was 30·9% (47/152), of which intracranial bleeding (ICH) was 34% (16/47). There were 96 thrombotic events (63·1%) consisting of venous 44·7% [68/152 of which 66·2% were pulmonary embolism (PE)], arterial 18·6% (13/152) and ECMO circuit thrombosis 9·9% (15/152). In multivariate analysis, only raised lactate dehydrogenase (LDH) at the initiation of VV ECMO was associated with an increased risk of thrombosis [hazard ratio (HR) 1·92, 95% CI 1·21-3·03]. Major bleeding and ICH were associated with 3·87-fold (95% CI 2·10-7·23) and 5·97-fold [95% confidence interval (CI) 2·36-15·04] increased risk of mortality and PE with a 2·00-fold (95% CI1·09-3·56) risk of mortality. This highlights the difficult balancing act often encountered when managing coagulopathy in COVID-19 patients supported with ECMO.
Asunto(s)
COVID-19 , Oxigenación por Membrana Extracorpórea , Hemorragia , SARS-CoV-2/metabolismo , Trombosis , Adulto , COVID-19/sangre , COVID-19/mortalidad , COVID-19/terapia , Supervivencia sin Enfermedad , Femenino , Hemorragia/sangre , Hemorragia/mortalidad , Hemorragia/terapia , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Trombosis/sangre , Trombosis/mortalidad , Trombosis/terapia , Reino Unido/epidemiologíaAsunto(s)
COVID-19 , Oxigenación por Membrana Extracorpórea , Neumonía Viral , Trombosis , Humanos , SARS-CoV-2RESUMEN
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 ß [IL-1ß] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.
Asunto(s)
COVID-19/metabolismo , Mielopoyesis , Neovascularización Patológica/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , SARS-CoV-2/metabolismo , Trombosis/metabolismo , COVID-19/patología , COVID-19/terapia , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Endoteliales/virología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteínas de la Membrana/metabolismo , Neovascularización Patológica/patología , Neovascularización Patológica/terapia , Neovascularización Patológica/virología , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/virología , Trombosis/patología , Trombosis/terapia , Trombosis/virología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
The impact of COVID-19 infection on pregnant women remains relatively unknown but the physiological changes of pregnancy and hypercoagulability of COVID-19 may further increase thrombotic risk. In this retrospective multicentre observational study, we report clinical characteristics and outcomes in 36 pregnant women requiring hospitalisation for COVID-19 compared to a propensity-matched cohort of non-pregnant women. Pregnant women had a lower haemoglobin and higher lymphocyte counts but no differences in other haematological or biochemical parameters on admission compared to non-pregnant women. There was no significant difference in the duration of hospitalisation; median two days (1-77) for pregnant versus eight days (1-49) for non-pregnant women. A higher proportion of non-pregnant women required mechanical ventilation [11/36 (31%) vs 3/36 (8%), P = 0·03] and received thromboprophylaxis with low-molecular-weight heparin (LMWH) within 24 h of admission [25/36 (69%) vs 15 /36(42%), P = 0·03] compared to pregnant women. One pregnant woman required extracorporeal membrane oxygenation. The rate of thrombosis was similar in both groups (one in each group). No women developed major bleeding or died. Data suggest that although non-pregnant women had a severe clinical course, overall outcomes were not different between women with or without pregnancy. The use of thromboprophylaxis was inconsistent, demonstrating a need for establishing evidence-based guidance for COVID-19 during pregnancy.
Asunto(s)
COVID-19/sangre , Trombosis/tratamiento farmacológico , Adulto , Femenino , Hospitalización , Humanos , Persona de Mediana Edad , Embarazo , Mujeres Embarazadas , Estudios Retrospectivos , Reino Unido , Adulto JovenAsunto(s)
Anticoagulantes/uso terapéutico , COVID-19/sangre , Enoxaparina/uso terapéutico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Riñón/fisiopatología , SARS-CoV-2 , Trombofilia/tratamiento farmacológico , Trombosis/prevención & control , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Peso Corporal , Proteína C-Reactiva/análisis , COVID-19/complicaciones , Relación Dosis-Respuesta a Droga , Enoxaparina/administración & dosificación , Femenino , Adhesión a Directriz , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Volúmen Plaquetario Medio , Persona de Mediana Edad , Oxígeno/sangre , Guías de Práctica Clínica como Asunto , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Trombofilia/etiología , Trombosis/epidemiología , Trombosis/etiologíaAsunto(s)
Anticoagulantes/administración & dosificación , COVID-19/complicaciones , SARS-CoV-2 , Trombosis de la Vena/prevención & control , COVID-19/virología , Toma de Decisiones Clínicas , Ensayos Clínicos como Asunto , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Duración de la Terapia , Humanos , Trombosis de la Vena/etiologíaAsunto(s)
Betacoronavirus/metabolismo , Infecciones por Coronavirus/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/complicaciones , Femenino , Humanos , Hipoxia/sangre , Hipoxia/etiología , Masculino , Persona de Mediana Edad , Pandemias , Perfusión , Neumonía Viral/sangre , Neumonía Viral/complicaciones , SARS-CoV-2Asunto(s)
Anticoagulantes/administración & dosificación , Betacoronavirus/metabolismo , Infecciones por Coronavirus , Pandemias , Ácidos Pipecólicos/administración & dosificación , Neumonía Viral , Trombofilia , Enfermedad Aguda , Adulto , Antitrombinas , Arginina/análogos & derivados , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/etiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neumonía Viral/sangre , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/etiología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Sulfonamidas , Trombofilia/sangre , Trombofilia/complicaciones , Trombofilia/epidemiologíaRESUMEN
This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID-19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.