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Exploring the Use of Plasma Viscosity Testing in Diagnosing COVID-19 Severity

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Following the recent publication of a study from Emory University that found elevated plasma viscosity levels in critically ill COVID-19 patients, a number of investigations are currently underway to understand the links between blood plasma thickness and COVID-19 severity.

To learn more about plasma viscosity and how it can be measured, as well as understand how this information could potentially be used to help diagnose and treat COVID-19 patients, Technology Networks spoke with Bernie Benson, MD of Benson Viscometers.

Anna MacDonald (AM): What is plasma viscosity (PV)?

Bernie Benson (BB):
Put simply, it is a liquid's resistance to flow, often it is referred to as the thickness of a liquid, in this case, blood plasma.

Increased plasma viscosity is an indicator for potential stroke and heart attack: these are induced by a low flow of blood in the capillaries leading to an inadequate delivery of vital oxygen and nutrients to body tissues.

A high plasma viscosity (hyperviscosity) can be linked to blood cancers including
polycythemia, macroglobulinemia, multiple myeloma, and leukaemia. Most recently, doctors at Emory University in the USA established that many COVID-19 patients had unusual blood clotting that failed to respond as expected to anti-clotting medication. Research identified that these patients had a high PV.

What can cause PV to rise above normal levels? What are the downstream effects of a raised PV?

The doctors at Emory University found that COVID-19 patients had extremely high levels of fibrinogen, a large protein that increases the blood plasma viscosity when in a high concentration. Fibrinogen is a key building block for making blood clots. Emory also found that patients with the highest viscosity levels were more likely to have blood coagulation problems e.g. excessive production of blood clots.

The majority of deaths attributed to COVID-19 are not respiratory but predominantly due to organ failure. A major contributing factor to this is the increased tendency of the patient's blood to thicken and the production of blood clots which can lead to heart failure, strokes, kidney failure and when formed in the lung, respiratory system failure.

AM: What have studies shown so far about the effect of SARS-CoV-2 infection on PV?

The doctors at Emory believe that the inflammation caused by the SARS-CoV-2 (COVID-19) infection causes the hyperviscosity (high PV), which may contribute to blood clots in some patients.  Cheryl Maier, Assistant Professor of Coagulation and Transfusion Medicine, Department of Pathology and Laboratory Medicine, Emory University School of Medicine and Medical Director of Emory’s Special Coagulation Laboratory said that “the viscosity levels in the sickest COVID-19 patients were similar to those seen in a type of blood disorder called hyperviscosity syndrome, where the high viscosity leads to dangerous sludging of the blood in the brain and other organs."

How can PV be measured? Can you tell us how viscometers work and the advantages they offer, especially when testing COVID-19 samples?

Clinical viscosity diagnostic tests are highly efficient as they can be carried out using the residue from the full blood count analysis, which would normally be carried out on a daily basis.  PV results are rapid, precise, and are not affected by variations such as gender, age, early pregnancy, or the presence of other conditions, such as anaemia.

An advantage of the PV test is that it will continue to give clinically significant results up to seven days after the sample has been taken. More importantly, the results are not altered or interfered with by the patient having taken medication such as high dose steroids, cytotoxic drugs or aspirin.

Daniel Gleghorn, Senior Biomedical Scientist - Automation Lead,Clinical Haematology, Cambridge University Hospitals NHS Foundation Trust stated: "PV testing is considered to provide a more useful indicator of infection, inflammation and malignancy than the traditional ESR test. It is also a cost-effective test compared with other expensive biochemical methods, can be performed on the same EDTA tube used for a full blood count and is quick and easy to perform."

Benson Viscometers’ clinical analysers facilitate the safe processing of high-risk samples as they incorporate “closed vial” sampling in their operation. This unique capability within our viscometers ensures direct exposure to the biological fluid is minimized as the sample tube cap does not need to be removed for the sample to be tested.

A number of studies are using Benson Viscometers’ equipment to investigate the links between PV and COVID-19, and explore the use of PV testing in diagnosing COVID-19 severity. Can you tell us more about these studies and what they hope to achieve?

Addenbrookes Hospital in the UK is using Benson Viscometers’ equipment to explore how best to understand and treat COVID-19. They have been carrying out the plasma viscosity test on all suspected COVID-19 patients to establish a link between PV and COVID-19 and to explore how PV relates to the severity of and/or recovery from the disease.

The tentative results so far, prior to sufficient statistical analysis, clearly show that there is an increase in the PV level associated with a positive COVID-19 result. It is believed that this indicates that PV has potential as a useful marker in the diagnostic assessment of patients with suspected COVID-19 and for monitoring the disease progression.

Health Services Laboratories (HSL) is also on the case. HSL’s flagship laboratory, The Halo in London (one of the largest pathology laboratories in Europe) is using the PV test to monitor inflammatory status in certain groups of COVID-19 patients, those with high risk TIA (transient ischaemic attack) commenced on DAPT (dual anti-platelet therapy), those with treatment failure on anti-platelet therapy, and those with high risk carotid/vertebral or intracranial stenosis.

This is to ensure anti-platelet drug therapy efficacy.

Could targeting raised PV be a potential therapeutic option for COVID-19 patients?

We believe it could. Doctors at Emory University are trying to determine the beneficial role of lowering the viscosity in COVID-19 patients through a treatment called plasma exchange. Cheryl Maier, MD, PhD, assistant professor of coagulation and transfusion medicine, Department of Pathology and Laboratory Medicine, Emory University School of Medicine and medical director of Emory’s Special Coagulation Laboratory, explains it like this: “During plasma exchange the plasma of COVID-19 patients is replaced with donated plasma. This reduces the viscosity by normalising the fibrinogen and other factors contributing to the stickiness and, potentially, may reduce clotting. Still, correlation does not mean causality, and we need to study this in large trials to understand whether viscosity is simply a marker of disease or actually contributing to clotting.”

Bernie Benson was speaking to Anna MacDonald, Science Writer for Technology Networks.