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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305693

ABSTRACT

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease-19 (COVID-19). Patients on oral anticoagulants prior to diagnosis of COVID-19 may therefore have better outcomes. We aimed:To first document the frequency of thrombosis, major bleeding and multiorgan failure (MOF) in patients admitted with COVID-19 and the contribution of these complications to 90-day mortality.To then determine the effects of oral anticoagulation, use prior to admission on the same outcomes as well as the requirement for Intensive Care Unit (ICU) admission, when compared to a propensity matched cohort of patients not taking oral anticoagulants prior to admission.Methods: This was a multicentre observational cohort including adult patients (≥18 years) admitted to 26 UK hospitals between 1st of April 2020 and 31 July 2020.Findings: A total of 5883 patients were included in the study. Overall mortality was 29.2%. Incidences of thrombosis, major bleeding and MOF were 5.4%,1.7% and 3.3% respectively. The presence of thrombosis, major bleeding, or MOF were associated with a 1.8, 4.5 or 5.9-fold increased risk of dying, respectively. Of the 5883 patients studied, 83.6% (n= 4920) were not on oral anticoagulants (OAC) and 16.4% (n=963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis (HR 1.05 (95%CI 0.93-1.19) P=0.15) or in an adjusted propensity score analysis (HR 0.92 (95%CI 0.58-1.450, P=0.18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulants prior to admission was treatment in ICU (HR 1.98 [95%CI 1.37-2.85]).Interpretation: Thrombosis, major bleeding, and MOF were associated with higher mortality. Our results indicate that patients may continue to benefit from OAC after admission, especially reduced admission to ICU, without any increase in bleeding.Funding: Bayer plc supported the study by providing the investigator-initiated funding (P87339) to setup the multicentre database of the study.Declaration of Interest: DJA received funding from Bayer plc to setup the multicentre database of the study as an investigator-initiated funding and received research grant from Leo Pharma. ML received consultation and speaker fees from Astra-Zeneca, Sobi, Leo-Pharma, Takeda and Pfizer. PN received research grants from Novartis, Principia and Rigel, unrestricted grants from Sanofi, Chugai and Octapharma and honoraria from Bayer. RA received fees from Alexion, Bayer, BMS, Pfizer and Portola. SS has received meeting sponsorship, speaker fees and/or consultancy from Bayer, Pfizer, NovoNordisk, Sobi, Chugai/Roche and Shire/Takeda. SS receives funding support from the Medical Research Council (MR/T024054/1). The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). SL has received speaker fees from Bayer, BMS and Pfizer. Others have no conflict of interests to declare. Ethical Approval: The study was approved by the Health Research Authority (HRA), Health and Care Research Wales (HCRW) and received local Caldicott Guardian support in Scotland (reference number: 20/HRA/1785). Data was collected both retrospectively and prospectively from patient clinical records by the treating medical team with no breach of privacy or anonymity by allocating a unique study number with no direct patient identifiable data;therefore, consent was waived by the HRA.

2.
Ther Adv Hematol ; 12: 20406207211048364, 2021.
Article in English | MEDLINE | ID: covidwho-1582496

ABSTRACT

BACKGROUND: COVID-19 patients present with both elevated D-dimer and a higher incidence of pulmonary embolism (PE). This single-centre retrospective observational study investigated the prevalence of early PE in COVID-19 patients and its relation to D-dimer at presentation. METHODS: The study included 1038 COVID-19-positive patients, with 1222 emergency department (ED) attendances over 11 weeks (16 March to 31 May 2020). Computed tomography pulmonary angiogram (CTPA) for PE was performed in 123 patients within 48 h of ED presentation, of whom 118 had D-dimer results. The remaining 875 attendances had D-dimer performed. RESULTS: CTPA performed in 11.8% of patients within 48 h of ED presentation confirmed PE in 37.4% (46/123). Thrombosis was observed at all levels of pulmonary vasculature with and without right ventricular strain. In the CTPA cohort, patients with PE had significantly higher D-dimer, prothrombin time, C-reactive protein, troponin, total bilirubin, neutrophils, white cell count and lower albumin compared with non-PE patients. However, there was no difference in the median duration of inpatient stay or mortality. A receiver operator curve analysis demonstrated that D-dimer could discriminate between PE and non-PE COVID-19 patients (area under the curve of 0.79, p < 0.0001). Furthermore, 43% (n = 62/145) of patients with D-dimer >5000 ng/ml had CTPA with PE confirmed in 61% (n = 38/62), that is, 26% of >5000 ng/ml cohort. The sensitivity and specificity were related to D-dimer level; cutoffs of 2000, 3000, 4000, and 5000 ng/ml, respectively, had a sensitivity of 93%, 90%, 90% and 86%, and a specificity of 38%, 54%, 59% and 68%, and if implemented, an additional 229, 141, 106 and 83 CTPAs would be required. CONCLUSION: Our data suggested an increased PE prevalence in COVID-19 patients attending ED with an elevated D-dimer, and patients with levels >5000 ng/ml might benefit from CTPA to exclude concomitant PE.

3.
Br J Haematol ; 196(1): 79-94, 2022 01.
Article in English | MEDLINE | ID: covidwho-1402884

ABSTRACT

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Thrombosis/complications , Thrombosis/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombosis/epidemiology , United Kingdom/epidemiology
4.
J Thromb Thrombolysis ; 51(4): 978-984, 2021 May.
Article in English | MEDLINE | ID: covidwho-1002140

ABSTRACT

Disordered coagulation, endothelial dysfunction, dehydration and immobility contribute to a substantially elevated risk of deep venous thrombosis, pulmonary embolism (PE) and systemic thrombosis in coronavirus disease 2019 (Covid-19). We evaluated the prevalence of pulmonary thrombosis and reported RV (right ventricular) dilatation/dysfunction associated with Covid-19 in a tertiary referral Covid-19 centre. Of 370 patients, positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 39 patients (mean age 62.3 ± 15 years, 56% male) underwent computed tomography pulmonary angiography (CTPA), due to increasing oxygen requirements or refractory hypoxia, not improving on oxygen, very elevated D-dimer or tachycardia disproportionate to clinical condition. Thrombosis in the pulmonary vasculature was found in 18 (46.2%) patients. However, pulmonary thrombosis did not predict survival (46.2% survivors vs 41.7% non-survivors, p = 0.796), but RV dilatation was less frequent among survivors (11.5% survivors vs 58.3% non-survivors, p = 0.002). Over the following month, we observed four Covid-19 patients, who were admitted with high and intermediate-high risk PE, and we treated them with UACTD (ultrasound-assisted catheter-directed thrombolysis), and four further patients, who were admitted with PE up to 4 weeks after recovery from Covid-19. Finally, we observed a case of RV dysfunction and pre-capillary pulmonary hypertension, associated with Covid-19 extensive lung disease. We demonstrated that pulmonary thrombosis is common in association with Covid-19. Also, the thrombotic risk in the pulmonary vasculature is present before and during hospital admission, and continues at least up to four weeks after discharge, and we present UACTD for high and intermediate-high risk PE management in Covid-19 patients.


Subject(s)
COVID-19 , Heart Ventricles , Pulmonary Embolism , Thrombolytic Therapy/methods , Ventricular Dysfunction, Right , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Computed Tomography Angiography/methods , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Organ Size , Outcome and Process Assessment, Health Care , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/etiology , Pulmonary Embolism/physiopathology , Risk Assessment , Risk Factors , SARS-CoV-2 , Ultrasonography, Interventional/methods , United Kingdom , Ventricular Dysfunction, Right/diagnosis , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/physiopathology
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