One of the biggest challenges facing medical teams treating Covid-19 patients is identifying which ones are likely to suffer the most extreme responses to the virus. Knowing this would make it possible to direct resources more efficiently and begin potentially life-saving treatment earlier.
A large proportion of Covid-19 patients recover without a serious illness, and while certain factors such as age, male gender, diabetes or obesity are known to increase the chances that a patient will have more serious complications, these alone do not give a clear prediction of how the disease will progress.
Now scientists believe they have an answer: a simple, affordable, well established blood test which essentially measures the thickness of blood and makes it possible to separate the patients that are mildly affected, are on the road to recovery or who are likely to deteriorate.
The test in question is clinical viscosity. Scientists have been measuring viscosity for over 100 years and easy to use analysers have been available for 50 years. Interest in and demand for clinical viscometers has increased following the discovery that severe Covid-19 patients have very significantly raised plasma and serum viscosity levels.
This is reported in the publication of a paper in the Lancet on 25 May 2020 by Cheryl Maier from Emory University, Georgia, Atlanta which demonstrated a dramatic rise of blood viscosity in severe Covid-19 patients. The sickest patients had the highest plasma viscosity levels, more than double normal values, and were also more likely to have a blood clot.
Despite having prescribed medications, known as blood thinners, to prevent blood clots in Covid-19 patients, clotting unusually still occurred. Although referred to as blood thinners, these medications would normally block factors involved in the clotting process as opposed to actually thinning the blood. As a result of this, it is believed that there is more to investigate within the blood coagulation process. Hyperviscosity may be an important piece of the puzzle in linking inflammation to clotting. Cheryl Maier said: “One thing that stood out was the extremely high levels of fibrinogen, a big sticky protein that increases with inflammation and is a key building block for making blood clots.”
Performing plasma viscosity measurements is a simple procedure when using viscometers specifically designed for clinical analysis. However, it appears that in north America, (USA and Canada) the majority of clinical laboratories are having to use viscometers that are designed for commercial use. Many publications on clinical viscosity from north America actually report a “relative” viscosity rather than a true viscosity. This is because the analysers in use have not been designed to be calibrated, to standardised international values, SI units.
The advantage of reporting an absolute viscosity value rather than a relative viscosity, is that absolute viscosities are scientifically a true value, independent of testing method and removes the potential for errors due to contamination of the water standard or the requirement to specify type of water used; e.g. tap water, distilled water, sterile water, de-ionised water etc. Results are then capable of being expressed in an internationally agreed standard format of Pascals second (Pa-s).
The main advantage of using a viscosity system which has been designed, calibrated and controlled for clinical analysis, compared to an adapted industrial viscometer is that a clinical viscometer has increased precision and sensitivity in the clinical relevant range of 1.2 to 10 mPa-s. Commercial viscometers tend to have an operating range of between 10 and 100,000 Pa-s.
Introducing clinical viscometers to pathology laboratories will enable clinicians to rapidly obtain results which can be easily interpreted for both plasma and serum viscosity, which for covid-19 patients will allow a simple rapid decision on which patients require more intensive therapy.
How can a combined plasma and serum viscosity be used and interpreted?
The key to predicting how a patients illness is progressing lies in comparing two different viscosity measurements, blood plasma and blood serum both of which can be carried out on modern clinical viscometers.
Plasma viscosity is mainly determined by the level of a blood clotting protein called fibrinogen and antibody concentrations produced by the body's immune system, when it detects and neutralises harmful substances. Dr.Cheryl Maiers Covid-19 patients had fibrinogen levels of up to five times the normal value.
Serum is a clear fluid released from blood when blood clots. There is no fibrinogen in serum as this is all used in the production of the clot. Serum viscosity levels are mainly dependent upon the number of antibodies, the fighting proteins present. So, an increased serum viscosity can indicate a strong antibody response to Covid-19.
Plasma viscosity raised with a normal serum viscosity
A raised plasma viscosity with normal serum viscosity indicates a raised fibrinogen concentration with no active antibody response present. These patients are probably deteriorating and will therefore be more likely to require intensive therapy.
Plasma viscosity and serum viscosity results both raised
If the plasma and serum viscosity analysis reveal that both results are raised, then the patient has raised antibody levels, and may also have a raised fibrinogen concentration.
These patients should have their fibrinogen concentration levels monitored to see if it is rising or falling. Rising levels of fibrinogen are indicative of the patient deteriorating. Falling levels could indicate that the patient may be recovering.
In either scenario, further observation and investigation of fibrinogen levels will be required.
Plasma viscosity and serum viscosity results both normal
If an individual has a positive Covid test result where both plasma and serum viscosity results are normal, they are probably asymptomatic but potentially a carrier.
Plasma viscosity normal with serum viscosity raised
This scenario is unlikely to occur because the proteins found in serum are also found in plasma. Therefore, a raise in serum viscosity would result in a raise in plasma viscosity.
Further advantages incorporated in modern clinical viscometers include:
Closed vial automated through seal sampling to reduce biohazard risk to laboratory operators
Fully automated sampling and automated system cleaning facilitates high sample throughput
Automatic programmed sterilisation and cleaning to remove sample contamination and carry over
Software that highlights clinically abnormal or significant results
Systems that can analyse from small sample volumes under 0.5ml
As only 50µl is used per test, repeat and paediatric tests can be carried out on the 0.5ml sample
Data transfer to clinical Laboratory Information Management Systems (LIMS) as standard
Able to carry out tests on sample tubes already used for other daily blood analysis such as the Full Blood Count minimizing need to draw additional samples from patients
Conform and support compliance with clinical laboratory regulatory requirements such as ISO:15189
Notes to editors
Benson Viscometers, based in Pembrokeshire, West Wales is a manufacturing company specialising in the design, development and manufacture of high-quality Clinical Viscometers and blood measuring equipment for hospital pathology laboratories.
Established in 1999, the family-run company has established itself as the leader in the provision of Clinical Viscometers throughout the UK. The majority of the clinical
analysers have been installed in National Health Service (NHS) Pathology laboratories, but private laboratories located in Europe and the USA also use our equipment.
The plasma viscosity test looks for abnormal proteins in the blood and is highly regarded as an important aid to diagnosis for a range of conditions, such as rheumatoid arthritis, myeloma and Waldenstrom macroglobuinaemia.
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