There is an urgent need to focus on medications that address dangerous blood clotting in Covid-19 patients, according to a leading haematologist.
Dr Pratima Chowdary, of the Royal Free London, UK, who is also co-centre director for the haemophilia centre at Health Services Laboratories and member of The Physiological Society’s Covid-19 Advisory Panel, said more than one third of Covid-19 patients are reportedly developing pulmonary artery thrombi.
These patients probably represent de novo thrombus formation, unlike the typical clots which represent an embolic phenomenon, she said.
“In other words, the clots of formed by new deposits in blood vessels rather than clots formed in other parts of the body that migrated,” she said.
“This might explain the slow onset of breathlessness. In some patients, a more typical rapid onset breathlessness secondary to rapid occlusion of the pulmonary vascular tree has been seen.
“I suspect a combination of both is common across the patient group, with the smaller peripheral thrombi representing de novo thrombus formation. The thrombi in the larger arteries probably are embolic in origin.”
She said while there has been an emphasis on anti-viral and anti-inflammatory strategies, studies addressing coagulation have struggled to be labelled as ‘important’.
“While anti-viral and potentially anti-inflammatory strategies may the control the ‘flood,’ i.e. viral infection and related cytokine storm, the ‘flood damage’ i.e. fibrin in the alveoli and bloodstream, needs to be addressed by alternate mechanisms,” said Dr Chowdary.
“An assumption has been made that managing the excess cytokines, and immune activation can address thrombosis. This is a misconception as our experience with other thrombotic conditions, including arterial and venous thrombosis shows that addressing the cause does not clear the clot.
“The clot is cleared through turnover process called fibrinolysis that is intrinsic to the coagulation process. This can also be facilitated by tissue plasminogen activator or streptokinase.”
The haematologist said elevated d-dimers – typically a four to ten-fold increase – has been seen in Covid-19 patients, while the sickest patients have had up to 150-fold increase.
A review of data shows that elevated d-dimers can predict the presence of pulmonary artery thrombosis.
While elevated d-dimers have been associated with higher mortality and morbidity, the relationship with the severity of lung disease remains unclear.
However, three possible mechanisms can be considered: the most prevalent is that coagulation abnormalities may be secondary to the cytokine storm. Another is that that the endothelium is damaged because of adjacency to the alveolar epithelium, and there is a spill-over of the severe inflammation, while the third possibility is that there is direct infection of the endothelial cells.
Regarding pulmonary artery thrombosis, Dr Chowdary said CT Pulmonary angiogram can demonstrate thrombi in pulmonary vasculature until the sub segmental level.
“It has been challenging in these patients as they are breathless with resulting motion artefacts, and the presence of lung pathology makes the smaller thrombi more challenging to visualise,” she said.
“If one accepts that the pulmonary thrombi are developing de novo, screening for them will become important as patients are unlikely to present with the more traditional clinical symptoms.”
Meanwhile, new research by Brighton and Sussex Medical School (BSMS), UK, has found that 7.7% of Covid-19 patients were diagnosed with venous thromboembolism, the most common type of which was pulmonary embolism, which was seen in 76.2% of 274 patients admitted to hospital.
Writing in the Clinical Medicine Journal, the research team found that the D-dimer blood test was useful to identify those patients at highest risk of venous thromboembolism when admitted to hospital.
Lead author Dr Chi Eziefula, senior lecturer in infection at BSMS, said: “Identifying which patients have a risk of, and clinical evidence of, a venous thromboembolism in Covid-19 is highly important for two reasons. Firstly, because venous thromboembolism is linked to a risk of death and secondly because it is treatable with anticoagulant medications.”
Source: Physiological Society/ Stoneham S, Milne K, Nutal E et al. Thrombotic risk in COVID-19: a case series and case–control study. Clinical Case Medicine May 2020
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