COVID-19 was originally thought to be an illness which affects the respiratory system, however over the past year considerable data has emerged suggesting COVID-19 increases coagulation abnormalities leading to arterial and venous thrombosis. Increasing research is being undertaken to understand how this occurs.

Thrombosis Australia presented a webinar with Prof. Huyen Tran (Australian Centre for Blood Diseases, Monash University) and Prof. James O’Donnell (Royal College of Surgeons, Dublin Ireland) to discuss relevant information and current research related to COVID-19 and thromboembolism.

The session was moderated by Dr Sally Cockburn. Dr Cockburn is a practicing GP and health educator. She has also been a high-profile media presenter for over 30 years on radio, TV and print.

These are a few topics of interest covered during the webinar.

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Do we know the mechanism causing the clotting?

For reasons we don’t understand

• some get an incredibly marked dysregulated proinflammatory response within the alveoli
• some get a secondary coagulopathy vasculopathy, particularly within the pulmonary microvasculature – leading to the formation of micro thrombi disseminated through the lungs
• causing a ventilation defect because the alveoli are full of inflammatory debris coupled with a profusion defect
• this is because you have these micro thrombi disseminated through the lungs and that VQ mismatch is causing the hypoxia and making the patients refractory to treatment

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What are the endotheliopathy markers?

• The von Willebrand Factor (VWF) is probably the easiest endothelial specific marker in the blood to monitor – they are certainly elevated
• Other more specialist tests;
  • P-selectin levels are increased;
  • von Willebrand Factor propeptide levels are increased
  • soluble thrombomodulin levels are increased

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People with von Willebrand disease?

• The ABO blood group affects von Willebrand factor levels
• Blood group O have 30% lower von Willebrand factor levels
• Genetic studies have clearly shown that blood group ABO is a determiner of risk
• People with blood group O have got less severe COVID than people who are not
• Therefore, basal VWF levels may actually be important in this context

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Current research with von Willebrand factor

• ADAMTS-13 (VWF cleaving protease – deficient in patients with TTP)
• There are quite a number of features of the microvasculature occlusion in COVID-19 that has some resemblance to certain aspects of the TTP illness
• The study is showing that the ADAMTS-13 levels are reduced in these patients; not as reduced as you would see in TTP but of course the VWF levels in COVID are increased 5-fold/10-fold, so that’s the highest VWF levels we have ever seen with any type of sepsis or cerebral malaria
• Therefore, there is an imbalance between the amount of VWF and the amount of cleaving protease present – suggesting VWF may play a role in the pulmonary microvasculature occlusions

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Current research by Prof. James O’Donnell

• Coagulopathy is not the same that we typically see in patients with severe viral infections
• Endothelial cells lining the blood vessels within the lung may be the key player in the whole process
• COVID-19 is different to other pneumonias as it diffusely affects both lungs
• The association of the inflammatory response to a large surface area of endothelial cells may be what is driving the pathogenesis of COVID-19
• Therefore, a one size fits all approach to treatment isn’t going to work
• Anticoagulation is useful but isn’t the whole story – by itself will not work for all patients
• We think that we are going to need;
  • Targeted anti-inflammatory therapies
  • Antiplatelet therapy
  • A type of endothelial cell targeting
  • And perhaps an anti VWF treatment for some people

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To watch the webinar in its entirety, please click this link.