A 10-fold and greater increase in D-dimer at admission in COVID-19 patients is highly predictive of pulmonary embolism in a retrospective cohort study.

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.

A Large London District General Hospital Highlights CLL and Bame As Risk Factors for Severe Disease Amongst Haematology-Oncology Patients

IntroductionThe earliest documented transmission of the coronavirus SARS-CoV-2, causing the disease Covid-19 occurred in the United Kingdom in February 2020. With data from Wuhan and Italy indicating a significant mortality rate in the region of 1-3% and identification of the risks of co-morbidities, hemato-oncology patients were quickly identified as being at a heightened risk from the virus due to baseline and chemotherapy induced immunosuppression. Data has shown that patients with cancer have a significantly higher incidence of severe events following infection with SARS-CoV-19 than those without cancer. Unlike many reported case series, our institution sees an unselected take of all hemato-oncology diagnoses within a large, ethnically-diverse locality and therefore provides an unfiltered snapshot of the impact of SARS-CoV-2 at an all-inclusive, population level.MethodsProspective data collection was carried out on all hemato-oncology patients admitted with a confirmed diagnosis of Covid-19 during March and April 2020 by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay on a nasopharyngeal aspirate across two sites in one of London's largest District General Hospital Trusts. Our institution has a catchment area of 810 000 heads of population of which 38-46.5% are of black, Asian and minority ethnic (BAME) ethnicity depending on locality.ResultsWe identified a total of 30 hemato-oncology patients admitted with PCR proven SARS-CoV-19. Their baseline characteristics are shown in figure 1. When compared with our cancer registry data (Fig 2A) this highlights a disproportionate representation of BAME patients (57% of cases vs 26% of base population). Lymphoid malignancies and plasma cell dyscrasias (PCD) accounted for 90% of the admissions. CLL and PCD accounted for 30% and 23% respectively (Fig 2C).Co-morbidities were less prevalent than those seen in patient cohorts without hematological malignancy. 70% of patients had </=1 co-morbidity and only 29% had >/= 2 comorbidities (Fig 2B) highlighting that, unlike other non-oncology series, hematological malignancy alone acts as a major risk factor for serious illness. Hypertension and Diabetes were the most common risk factors, seen in 50% and 43% of patients respectively.The most common presenting features were cough (84%), fever (72%) and shortness of breath (80%). 16% had Gastrointestinal symptoms, but only seen in the context of concurrent respiratory symptoms. The vast majority (84%) had radiological changes consistent with a diagnosis of COVID-19.Our cohort had a mortality rate of 47%. Of those that died, 57% were from BAME groups and 43% were White. 71% of those that died had either CLL (6/14 cases) or multiple myeloma (MM) (4/14 cases). CLL appears to be an independent risk factor from age, as two of the patients with CLL that died were amongst the youngest in our cohort (47 years and 59 years). Two patients that died had Myelodysplastic syndrome, one had Diffuse large B cell lymphoma and one had Hodgkin's lymphoma. We found that age and number of co-morbidities were positively associated with death. Of the patients that died, 79% were 70 years of age or over and the majority of survivors were 60 years old or younger (56%). Lymphopenia was a consistent finding at diagnosis (median lymphocyte count 0.8 x 109/l), neutropenia was rare (median neutrophil count 5.9 x 109/l) and C-reactive protein was elevated in all cases (median value 169, range 42-473 mg/l).Of our 4 patients with plasma cell dyscrasias who died, 2 had end stage myeloma (4th line+ of therapy), 1 had primary refractory MM and 1 had plasma cell leukaemia, thus identifying these patients as extremely high risk from the outset.ConclusionIt is of great importance to identify patient and disease specific risk factors conferring poor risk amongst our hemato-oncology patients. With shielding, invariably comes the increased risk of morbidity from social isolation and delayed presentation of non-COVID illness. Our data shows that CLL and BAME patients appear to be at particular risk of sever illness and poor outcomes. In a local ethnically diverse population, our patients are at heightened risk of morbidity and mortality and must be offered all strategies for interventions that may reduce likelihood of becoming infected with COVID 19 and should be considered early for vaccination, convalescent plasma and monoclonal antibodies.

Pulmonary thrombosis in Covid-19: before, during and after hospital admission.

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.