HAEMATOLOGY
example, anticoagulants do not improve outcomes; instead the inflammatory process is treated.
Hypoxia through transcription factors is also found in COVID patients, which leads to a prothrombotic state. “We are admitting patients with COVID-19 because they are hypoxic and the degree of hypoxia determines whether they end up on a ventilator in ICU or on the ward receiving supplementary oxygen,” she commented. She explained that, in patients with COVID-19 pneumonia, acute lung injury leads to a profound inflammatory state. “When we look at the histopathology of the pneumonia, we are seeing massive invasion of the lungs with macrophages and lymphocytes. “We see areas of focal haemorrhage and we also see areas where fibrin has been laid down. We know the result of acute lung injury is the cytokine storm,” commented Prof. Hunt, adding that ferritin, CRP, D-dimer and fibrinogen become extremely elevated, with a marked acute phase response. “In all my long career, I have never seen people with such high levels of fibrinogen. It is usually 3-4g per litre…but we are seeing levels of 10-14g per litre in some patients with COVID-19,” Prof. Hunt continued. She stated that the evidence points to the fact that thrombosis is occurring secondary to inflammation and hypoxia, in COVID-19 patients, rather than this being a primary thrombotic process.
She gave her view on what is likely to be happening in COVID-19 patients: “COVID-19 enters through the ACE2 receptor on the pulmonary epithelium, but it is also on the macrophages and endothelium. There is a lack of clarity whether it is expressed in all the endothelium or just some areas in particular. I would put money on the small bowel endothelium and the large vessels. “We know that if you get COVID, it will be seven to ten days, then the minority (5-10%) will go on to get COVID pneumonia. It is at that point we are seeing these profound changes in coagulation, in inflammation and cytokine storm, with endothelial and macrophage activation. I am just waiting for the paper to say there is platelet activation too. “So, we are seeing a marked prothrombotic state due to the effects of IL1 and IL6. I am interested in why it happens in certain groups – does a pre-existing inflammatory state make COVID-19 pneumonia more likely – e.g. artherosclerosis, obesity and diabetes?” Prof. Hunt highlighted the fact that the BMI is >25 in 75% of UK patients with severe COVID-19 and obesity is common. The children that have gone on to get the inflammatory response have also tended to have a BMI of around 28. Hypertrophic adipocytes (like atherosclerosis and diabetes) induce an inflammatory state, she explained.
OCTOBER 2020
New data shows hospitalised COVID
survivors make the best plasma donors New data shows people who were hospitalised by COVID-19 produce the most antibodies, making them priority plasma donors. Analysis of donations shows 76% of positive tested people who were hospitalised had high enough antibody levels for their donation to be used in the national trial. In comparison, 30% of positive tested people who did not need hospital treatment had high enough antibody levels. NHS Blood and Transplant is currently urgently appealing for donors, especially men, ahead of any second wave. All offers to donate are welcome, including
from men who had the symptoms but no test. However the new data highlights the importance of donations from people who needed hospital care.
Plasma from people who have recovered from COVID-19 can be transfused into people who are still unwell and struggling to develop their own immune response. The plasma contains neutralising antibodies which could stop the virus spreading. NHS Blood and Transplant’s Clinical
Trials Unit is collaborating with the RECOVERY and REMAP-CAP platform trials on two randomised control trials.
She moved on to examine the risk of VTE in critical care. At the turn of the century, without thromboprophylaxis, the figures were around 28%. With thromboprophylaxis, this is dramatically reduced, so rates of around 10% can be expected. Risk factors include increasing age, acute infective illness, venous lines, underlying patient risk factors and immobility.
She added that the evidence shows that low molecular weight heparin is better than Unfractionated Heparin (UFH). “We have profoundly sick patients that have been ventilated, with prothrombotic status, and then we are sending them home. So, should we send them home on some form of thromboprophylaxis? We know that if we give people low molecular weight heparin after they have gone home, they have a lower rate of VTE, but the bleeding risk increases, and the overall effect is no benefit,” she commented. However, she added that trials have looked at the use of Apixiban, Rivaroxaban
and Betrixiban and the data now shows that a low dose of direct oral anticoagulant (DOAC) has a positive effect. The criteria for extending prophylaxis include: l Age ≥75 years l Past history of Cancer or VTE; or l EXtra risk factors
Known risk factors for VTE include: D-dimers
≥2 upper limit of normal range, ICU stay, or two other factors such as past history of superficial VT, obesity, varicose veins, chronic venous insufficiency, lower extremity paresis, hormone therapy, thrombophilia (congenital or acquired), concomitant use of erythropoiesis stimulating agents. Based on these criteria, Prof. Hunt suggested that COVID-19 patients should be considered for extended thromboprophylaxis. In the UK, inpatients receive
thromboprophylaxis according to their risk assessment, as standard practice. However, In China, COVID patients were not routinely given heparin until quite late during the pandemic.
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