26 May 2020

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, gave her thoughts in an interview for the Physiological Society, which she is a member of their COVID-19 Advisory Panel. The interview follows an article from the BBC which reports that up to a third of COVID-19 patients are developing dangerous blood clots.

Dr Chowdary says that the clots in 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 trialling anti-viral and anti-inflammatory strategies, studies addressing coagulation have struggled to gain the same traction.

“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.

Dr Chowdary says that review of data at her institution 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. The third possibility is that there is direct infection of the endothelial cells.

Regarding pulmonary artery thrombosis, Dr Chowdary said a CT pulmonary angiogram can demonstrate thrombi in pulmonary vasculature down to 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) has found that 7.7% of COVID-19 patients were diagnosed with venous thromboembolism (VTE). In the series of 274 patients admitted to hospital, the most common type was pulmonary embolism, which was seen in 16 of the 21 of the patients with VTE.

Writing in the journal Clinical Medicine, the research team found that the D-dimer blood test could be 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: https://www.physoc.org/news_article/expert-reaction-to-high-proportion-of-blood-clotting-in-covid-19-patients/

Stoneham SM, Milne KM, Nuttal E, Frew GH, Sturrock BR, Sivaloganathan H, Ladikou EE, Drage S, Phillips B, Chevassut TJ, Eziefula AC (2020) “Thrombotic risk in COVID-19: a case series and case–control study”, Clinical Medicine, doi: 10.7861/clinmed.2020-0228


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