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Benson Viscometers Ltd.

Croft Quarry West Williamston, SA68 0TN Kilgetty
United Kingdom of Great Britain and Northern Ireland

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This company is co-exhibitor of
Wales Government

Contact

Lorna Chun

Company General Manager

Phone
01646650065

Email
lorna@bensonviscometers.com

Jan Bojanowski

Operations Manager

Phone
01646650065

Email
jan@bensonviscometers.com

Bernie Benson

Managing Director

Phone
01646650066

Email
bernie@bensonviscometers.com

Our range of products

Product categories

  • 02  Laboratory technology
  • 02.01  Analyser systems / equipment
  • 03  Diagnostic tests
  • 03.02  Immunochemistry testing, immunology testing
  • 03.02.04  Other equipment for immunochemistry and immunology

Other equipment for immunochemistry and immunology

  • 03  Diagnostic tests
  • 03.03  Haematology / histology / cytology testing
  • 03.03.01  Haematology analyzers

Our products

Product category: Analyser systems / equipment, Other equipment for immunochemistry and immunology, Haematology analyzers

BV200 Clinical Viscometer

  • The Benson Viscometers BV200 Clinical Viscometer measures the viscosity of clinical human biological fluids; blood plasma, blood serum, whole blood, and synovial fluid. It is an in-vitro analyzer for use in a pathology laboratory environment by trained laboratory professionals.

    It is a fully-automated analyzer. When the operator has carried out a simple daily maintenance program and initiated the testing procedure it will process patient test samples, calibration, check quality controls, system washing, system enzymatic cleaning, and system sterilization. The operator must attend the analyzer to load un-tested patient samples and controls and remove tubes that the instrument has processed.

    The principle of operation of the BV200 is a capillary viscometer that draws a sample of liquid through a temperature-controlled (37℃) calibrated capillary tube using a pre-set known force in the form of a regulated vacuum. The time for the fluid to pass two known points is measured and recorded. This ‘runtime’ is used to calculate the dynamic viscosity of the fluid.

    The BV200 viscometer can be used with biological fluids that are considered to be bio-hazardous by utilizing the ‘through cap piercing capability’ where the sample tube cap does not need to be removed.

    ·       The BV200 clinical viscometer will measure the viscosity of human biological fluids: blood plasma, blood serum, whole blood, and synovial fluid

    ·       The BV200 analyzer regularly processes in excess of 400 samples a day

    ·       It will test directly from primary blood sample tubes reducing biohazard risks

    ·       Uses the residue from the full blood count tubes eliminating additional sample requirements

    ·       Through cap piercing capability reducing biohazard risks

    ·       Accommodates tubes from all leading blood collection tube manufacturers

    ·       Aspirates only 50µl per test. Only requires 500µl of sample fluid

    ·       Therefore it is suitable for repeat testing of paediatric and adult samples

    ·       Can be loaded with up to 180 patient samples at a time

    ·       Fast, 15 minute turn around time from sample receipt to results

    ·       Automatic barcode reading immediately prior to analysis

    ·       Load and walk away system

    ·       Automatic calibration checks every 10 patient samples

    ·       Network interface capability

    ·       Sample and wash carry-over level of <0.01 mPa.s

    ·       Operator password logon

    ·        Tests at 37°C, reports at 25°C or 37°C

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Product category: Analyser systems / equipment, Other equipment for immunochemistry and immunology, Haematology analyzers

BV1 Clinical Viscometer

The Benson Viscometers BV1 Clinical Viscometer measures the viscosity of human biological fluids; blood plasma, blood serum, whole blood, and synovial fluid. It is an in-vitro analyzer for use in a pathology laboratory environment by trained laboratory professionals.

It is a semi-automated instrument, for which the operator is present to process patient test samples, calibration, check quality controls, system washing, system enzymatic cleaning, and system sterilization.

The principle of operation of the BV1 is a capillary viscometer that draws a sample of liquid through a temperature-controlled (37℃) calibrated capillary tube using a pre-set known force in the form of a regulated vacuum. The time for the fluid to pass two known points is measured and recorded. This ‘runtime’ is used to calculate the dynamic viscosity of the fluid

The BV1 viscometer can be used with biological fluids that are considered to be bio-hazardous by utilizing the ‘through cap piercing capability’ where the sample tube cap does not need to be removed.

·       The BV1clinical viscometer will measure the viscosity of human biological fluids: blood plasma, blood serum, whole blood, and synovial fluid

·       The BV1 analyzer is ideal for processing up to 50 patient samples a day

·       It will test directly from primary blood sample tubes reducing biohazard risks

·       Uses the residue from the full blood count tubes eliminating additional sample requirements

·       Through cap piercing capability reducing biohazard risks

·       Accommodates tubes from all leading blood collection tube manufacturers

·       Aspirates only 60µl per test. Only requires 500µl of sample fluid

·       Therefore it is suitable for repeat testing of paediatric and adult samples

·       Fast, 15 minute turn around time from sample receipt to results

·       Barcode reading immediately prior to analysis

·       Operator is present to process patient test samples

·       Automated calibration checks every 6 patient samples

·       Network interface capability

·        Sample and wash carry-over level of <0.01 mPa.s

·        Tests at 37°C, reports at 25°C or 37°C

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Nov 13, 2020

Plasma Viscosity - Accuracy, Precision and Suitability – who wants it?

Since 1947, when John Harkness published his seminal work on clinical plasma viscosity analysis in the British Medical Journal, the test has been generally misunderstood and certainly underutilised. With the infection of humans by SARS Cov2 since late 2019, the pandemic has forced scientists to take a fresh and detailed look at infections and PV; not just PV per se, but its values, trends and the fact it can be used in the calculation of a possible predictor of severity. The world may well now see that Professor Harkness was a man before his time, and he will posthumously receive his due recognition. In May 2020, a paper published in the Lancet from a team at the Emory Medical Centre in Atlanta Georgia showing that Covid-19 patients who developed severe symptoms had markedly raised plasma viscosity levels. This raised the profile of the test among medical and scientific professionals trying to cope with the new pandemic. (COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia? Cheryl L Maier Alexander D Truong Sara C Auld Derek M Polly Christin-Lauren Tanksley Alexander Duncan The Lancet Volume 395, ISSUE 10239, P1758-1759, June 06, 2020)

During the 70+ years since Harkness’s work, there have been many publications confirming the clinical value of using plasma viscosity for investigating patients with an acute phase response or with paraproteins. In early publications plasma viscosity was compared against the established erythrocyte sedimentation rate (ESR), and later against both the ESR and the C-reactive protein (CRP). The plasma viscosity test was reported on very favourably by many of the papers.

Acute Phase Response

In the acute phase response patients produce increased quantities of immunoglobulins (antibodies), the blood clotting protein fibrinogen, CRP and various inflammatory cytokines (signalling proteins).

Plasma viscosity is determined by 2 factors:

·         The concentration of proteins

·         The shape of the molecules

Antibodies and fibrinogen are found at high concentrations in human plasma. The shape of their molecules has a high length to width ratio, which is the shape that increases the viscosity the most. This means that viscosity measurements are extremely sensitive to increased levels of these proteins. 

As long ago as 1988, the world’s leading haematologists recognised the value of the plasma viscosity test for monitoring the acute phase response. Published under the auspices of the International Committee for Standards in Haematology  they published a guidance paper on methods for investigating acute phase response and stated “Measurement of plasma viscosity has several advantages over the ESR, including independence from the effects of anaemia; a single reference range that is independent of sex and less dependent on age; instruments that can be calibrated; convenience of quality control checks; and results that are available within 15 minutes.(Guidelines on selection of laboratory tests for monitoring the acute phase response INTERNATIONAL COMMITTEE FOR STANDARDIZATION IN HAEMATOLOGY(EXPERT PANEL ON BLOOD RHEOLOGY) J Clin Pathol 1988;41:1203-1212)

Some laboratories perform the PV test in preference to the ESR and often clinicians will be advised to use the PV test in preference (https://www.gloshospitals.nhs.uk/our-services/services-we-offer/pathology/tests-and-investigations/plasma-viscosity/).

PV is no longer just a non-diagnostic support test and an alternative to ESR. It is much more than that and is probably a better test to reflect plasma protein changes in such inflammatory conditions as polymyalgia rheumatica.

Feedback from laboratories suggest many benefits plasma viscosity testing, not just to patients, but also clinicians and from a laboratory management perspective.

It is a cost-effective test and efficient to perform
Automatable, and can be performed on existing EDTA samples as it uses a small sample volume
Safer for high-risk samples such as Covid-19 as it can be performed on sealed tubes
Easy to perform and tests are completed in minutes with results reported to any LIMS
Modern clinical viscometers have the capability for serum viscosity (SV) to be performed without any changes to equipment or additional reagents
Clinical viscosity is a known measure of inflammatory response with the potential to be a measure of recovery and/or antibody response especially if combined PV/SV is performed as this will exclude the increased acute phase response of fibrinogen
Clinical viscosity results become abnormal earlier in disease than ESR and is not affected by haematocrit
Has a much lower instance of false normal values
Performing a PV test has practical advantages for a laboratory as it can be carried out on a sample up to 7 days after blood being drawn compared to an ESR which has to processed within 4hrs. This makes PV ideal for rural areas or when the test is outsourced
Relatively small changes in PV from the norm are clinically significant for any individual
Clinical plasma viscosity testing is technically reproducible and standardised
PV is more informative and stable than ESR. It has a definitive numerical result that can be easily referenced against condition charts
It is expected that the PV value will be increased in any infection but if clinicians look beyond that they can follow trends through daily monitoring that will correlate with severity.

Clinical viscosity can be used to calculate the rigidity (flexibility) of red cells in a way no one has practiced previously. This has enormous potential for patient benefit.  With the addition of SV it adds another dimension of possibility. 

The ratio of the two could prove remarkably interesting clinically. There remains the question of why some BAME (Black, Asian, and minority ethnic) patients are more susceptible than their Caucasian (white European ancestry communities) equivalents.  Can this be detected by PV, SV, or a combination of the two?

One condition where early diagnosis is vital is giant cell arteritis.  A paper published by Gudmundsson in 1993 stated that PV was better than both the ESR and CRP for predicting flare ups in the condition (Plasma viscosity in giant cell arteritis as a predictor of disease activity. M Gudmundsson, E Nordborg, B A Bengtsson, and A Bjelle Ann Rheum Dis. 1993 Feb; 52(2): 104–109.)

In 2011 Finke went even further, stating in his study that it appeared that the plasma viscosity test measured a more specific inflammatory marker for giant cell arteritis than either the CRP or ESR and in patients outside the criteria suggested by the American College of Rheumatology “plasma viscosity may significantly contribute to a reliable diagnosis early in the course of the disease”. (Plasma Viscosity in Giant Cell Arteritis:   Carsten Finke Jan Schroeter Ulrich Kalus Christoph J Ploner : September 2011 European Neurology 66(3):159-64)

 

PARAPROTEINS

Conditions that produce paraproteins include the myelomas and lymphomas. Paraproteins are immunoglobulins (antibodies) which are produced in abnormally large quantities by malignancies of the lymphoid B cell lineage. During the last 50 years in the United Kingdom (UK), plasma viscosity has been, and still can be, used to screen for and monitor the paraproteinaemias.

Myeloma

Early diagnosis of Myeloma is important as the malignancy is easier to treat the earlier it is diagnosed. However, early symptoms are not specific, and this rare condition is difficult to diagnose in primary practice. A paper published in the British Journal of General Practice in 2018 showed that in conjunction with a normal haemoglobin concentration, a normal plasma viscosity level could be used to rule out the disease. Researchers also said that GPs should use simple blood tests to support symptoms when diagnosing patients with multiple myeloma, in order to improve early detection rates and that plasma viscosity was one of the best inflammatory markers to supplement symptoms. (Early detection of multiple myeloma in primary care using blood tests: a case–control study in primary care: Br J Gen Pract. 2018 Sep; 68(674))

Going as far back as 1974, 4 cases of IgA multiple myeloma with raised serum or plasma viscosity and clinical features of hyperviscosity syndrome were reviewed. It was felt that serum viscosity measurement was essential for rational clinical management (https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1974.tb06775.x)

A specific condition, Waldenstroms Macroglobulinaemia, causes an increase in a class of immunoglobulin called IgM. IgM protein is a large asymmetrical molecule which causes the blood viscosity to rapidly rise to levels which cause major organ damage. Monitoring the patient by plasma viscosity analysis can lead to earlier treatment, thus reducing the risk of hyperviscosity syndrome. For those patients who do develop hyperviscosity syndrome the treatment is frequently a plasma exchange and using the plasma viscosity test to monitor the treatment, clinicians can rapidly determine if sufficient rounds of treatment have been undertaken.

Benefits Realisation from Plasma Viscosity Analysis

As demonstrated above there is a lot of literature available demonstrating that plasma viscosity is a clinical test which can help in the diagnosis and treatment of several conditions. The test has been available for over 70 years and yet it is still not fully understood, why?

The main reason appears to be a misconception that performing a plasma viscosity test is difficult to do. This probably was the case until the 1980s. In the UK, Coulter Electronics developed a semi-automated plasma viscometer (Visco II) which allowed batch analysis. Plasma could be put in cups on a carousel and the machine automatically sampled and analysed. However, the parent company did not market the device in the USA and in the 1990s Coulter UK withdrew the product. Most of the world were therefore left to use adapted (or not) industrial viscometers to analyse clinical samples. These devices were time consuming to use and had little or no clinical calibration. This has led to a significant number of papers publishing results as relative viscosity. That is comparing the viscosity to the viscosity of water.

Another issue has been using the wrong type of viscometer. The Coulter Visco II was designed as a clinical instrument, calibrated within the range of plasma viscosities and most importantly was a capillary viscometer. It also reported in SI units, meaning all machines gave the same results for the same sample (within manufacturing tolerance).Capillary viscometers are suitable for use on Newtonian fluids like blood plasma and serum, they also have the advantage that a calibrant can be analysed with each batch or number of tests and they can be easily cleaned automatically by sampling and processing a cleaning reagent.

Historically, the USA continued to mainly use industrial cone and plate technology which lose the benefits of capillary analysers. The cumbersome cleaning requirements, lack of standardisation and SI reporting units made clinicians sceptical of the results and hence the test.

In recent years there has also been a drive to reduce costs within the NHS across the UK. Pathology tests were highlighted as an area which were associated with substantial spending. GPs were directed to be more selective in their requests for a diagnostic test and to reduce the number of tests they requested as it was identified that often GPs would request multiple tests which, in some cases, were seen to overlap or duplicate (https://bjgp.org/content/66/644/e200).

However, this activity has led to several outcomes. The ability to readily request certain tests have been made more difficult, this in turn has led to a decline in some tests being requested which has ultimately led to inefficiencies in delivering the ability to conduct the test and a perception that these tests are expensive as there is no longer the economies of scale. There has been an increase acceptance of less appropriate tests as meeting the clinical need and a mindset of “it will do”. The strive for clinical excellence has been overtaken by thoughts of money and the strategic activities to save it. Whilst value for money is a worthwhile goal, there should be no compromise to patient care.

There is immense scope for the education on clinical viscosity testing to be enhanced and improved to incorporate its full potential and to raise the vision in the possibilities it has to improve patient outcomes and to provide invaluable information to clinicians. Incorporating clinical viscosity testing globally into associated condition pathways, will encourage and ensure clinical excellence, consistency and equity for patients.

So What Has Changed?

Two things have changed, the first is that clinical capillary viscometers have continued to develop, and now clinical viscosity analysers are available with advanced health and safety features, increased throughput, improved reliability, and most importantly improved precision. There is now true load up and walk away analysers that sample from a sealed, cap on primary (draw) tube to avoid potential biohazards, which incorporate software to perform auto calibration and quality control checks between every few samples to monitor for drift. Viscometers which have been specifically designed and manufactured for clinical use should be the only standard any healthcare provider accepts.

The second change is Covid-19. Clinicians around the world are trying to establish a strategy to determine which patients infected with SARS Cov2 develop severe non respiratory complications. So far, the key screening test appears to be the plasma viscosity test. As stated in the introduction patients suffering with severe Covid-19 symptoms have a greatly raised plasma viscosity level. This is expected because they will develop an acute phase response and indeed, they produce a mega response with fibrinogen levels up to 10 times the norm, with a subsequent rise in the plasma viscosity to levels only previously seen in patients with hyperviscosity syndrome.

Recent research illustrates a significant change in some of these parameters in the immediate time leading up to symptoms developing which is potentially an exciting finding and might save the lives of many patients by early diagnosis and specific targeted treatment. Leading hospitals are exploring how best to understand and treat Covid-19. They have been carrying out the plasma viscosity test on 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. This has extended to ensuring anti-platelet drug therapy efficacy by monitoring the inflammatory status in those with high risk TIA (transient ischaemic attack) commenced on dual anti-platelet therapy, those not responding as expected on anti-platelet therapy, and those with high risk carotid/vertebral or intracranial stenosis. Increased blood viscosity is an indicator for potential stroke and heart attack induced by a low flow of blood in the capillaries leading to an inadequate delivery of vital oxygen and nutrients to body tissues.

Haematology experts have stated that while there are alternative tests for inflammation and infection none of them surpass the accuracy, precision, and suitability of PV for diagnosis and monitoring. There are constantly new applications found for PV, SV and red cell deformability on an almost daily basis and none more so than in the current climate of battling Covid-19. 

The significance of these developments should not be underestimated. Gregory Sloop, Associate Professor of Pathology, Idaho, wrote in a recent article on Medium.com: “Regarding the unusual presentations of Covid-19, Yale School of Medicine cardiologist Harlan Krumholz, M.D. said ‘Our ignorance is profound’. Much of this mystery stems from ignoring blood viscosity. Because blood viscosity is inversely related to blood flow, elevated blood viscosity increases the risk of clotting and causes hypoxemia.” 

With the USA seeing many Covid-19 patients, clinical establishments are undertaking research into the condition and are publishing papers with plasma viscosity data; Some using outdated cumbersome equipment inherited from the petrochemical industry. USA medical centres are starting to look to the UK for state-of-the-art clinical equipment that will allow them to rapidly and safely analyse high risk clinical samples. And when the USA leads, the rest of the world follows.

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Nov 13, 2020

Blood Viscosity: The Test that can Save The World?

2020 has been a strange year all round. An unknown virus, probably originating in a bat colony in central China, mutated to allow it to also infect humans. Within three months of the virus being identified as Corona Virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), 90% of the world had shut down.

Health care systems within the developed world were stretched to the point of collapse, old people were left to die in several “civilised countries”; world travel was stopped; many countries borrowed or printed money several times their GDP and political leaders fell in to two camps. One set of world leaders went in to political denial, "we will carry on as normal",  "pandemics will not affect our modern nation"; the other set went in to meltdown and locked down their countries with severe long term financial consequences. Neither reaction has protected the health or wealth of their population. Whether health or wealth has been damaged the most is yet to be determined, and maybe over time it will turn out that there is truly little difference.

Whatever the political reaction has been to the virus infecting their country’s population, the majority of leaders appeared to believe that medical science was going to miraculously save them from a problem over which they had neither knowledge nor control.

The overriding mantra was "our scientists will soon produce a vaccine which will save our population and our political skins"; meanwhile the virus, oblivious to the turmoil, marched on. Countries that had hoped to carry on regardless, soon found that they had a mounting death toll that they were being blamed for by not locking down effectively.

Those countries that had locked down rapidly, quickly realised that they had no way of maintaining lockdown either physically, or financially, until such time as a vaccine becomes available. Moving out of lockdown is proving to be a lot more difficult than imposing it in the first instance.

At the time of writing there is a realisation that the virus, or rather the disease caused by the virus, Covid-19, is here to stay, and we need to learn how to live with it.

Over the last 4 or 5 months, world scientists have collaborated to such an extent that, whereas 6 months ago, no one had heard of SARS- CoV- 2 or Covid-19, they now know its full genome, and how it can infect the human body. They also know that unlike any other Severe Acute Respiratory Syndrome, SARS- CoV- 2 does not produce a pure respiratory illness.

 In fact, most deaths attributed to Covid-19 are not respiratory but predominantly due to organ failure. A major contributing factor to this is the increased tendency for blood clots to form which leads to heart failure, strokes, kidney failure and when formed in the lung, respiratory failure. In short, the sickest Covid-19 patients suffer from multi organ failure.

Medical teams treating Covid-19 patients have faced a dilemma. For some time, it has been known that the majority of patients who contract Covid-19 infections do not develop a severe illness. However, the minority who do are strongly linked with other factors that increase the risk of ill health, such as being older, having heart or respiratory problems, having diabetes or being obese. Despite knowing these risk factors, there is no indication whether an individual patient will go on to develop severe symptoms. Medics around the world do not know which patients to monitor or treat until it is too late, by which time, the patient already has a severe condition which is extremely difficult to treat, and even if successfully treated, may leave them with long lasting health issues requiring long term support.

Now, what would the medics around the world say if there was a cheap simple blood test that could divide these patients in to the two groups, those that need treatment and those that don’t?

This is where clinical viscosity measurements come in. Clinical viscosity measurements have been reported in literature for over 100 years and easy to use analysers have been available for 50 years. Full clinical blood viscosity analysis requires 3 distinct analyses: -

Whole blood viscosity

      Whole blood viscosity measures a sample of blood containing all the fluid and cellular constituents. The main factor affecting blood viscosity is the red cells, both their volume, usually taken as the haematocrit, and their ability to change shape.

Plasma viscosity

      Plasma viscosity measures the viscosity of blood fluid with all the cellular components removed. The key factors affecting plasma viscosity are the fibrinogen concentration and antibody levels. More of which later.

Serum viscosity

      Serum viscosity measure blood fluid after the blood has clotted and therefore does not contain several of the factors required in blood clotting, of which fibrinogen is one. Therefore, the main factor to affect serum viscosity is antibody concentration.

In current practice whole blood viscosity measurements are time consuming and difficult to perform.  Many analysers require measurements at varying shear rates on the same sample. Fortunately, in Covid-19 patients, the most valuable information is obtained from plasma and serum viscosity analysis.

There are numerous reports that severe Covid-19 patients have raised blood viscosity levels. More significantly, these patients have raised plasma and serum viscosity levels.

A paper published by Emory University; Georgia Atlanta in the Lancet 25 May 2020 by Cheryl Maier demonstrated a dramatic rise in severe Covid-19 patients of more than double the normal value. This paper also linked the rise in viscosity to patients with severe clotting risks.

An understanding of what is being measured in plasma viscosity makes this link an obvious one. As mentioned earlier in this article, plasma viscosity is mainly affected by fibrinogen and antibody concentrations in the patient. Fibrinogen is the compound that is the precursor to the fibrin strands that form a blood clot. In normal human blood it is found at a concentration of 1.5 to 4.0 gms/l. In Dr Maiers Covid-19 patients she found they had fibrinogen levels of up to 5 times the normal value. It could therefore be inferred that patients with a high or rising plasma viscosity are the patients that are going to have or develop severe multi organ failure. Unfortunately, as with most aspects of the Covid -19 infection, things are not that simple.

Both fibrinogen and antibody levels affect the plasma viscosity so, a raised plasma viscosity cannot be attributed to fibrinogen concentrations without further testing. Although this is possible, fibrinogen analysis requires further blood samples to be taken and is a relatively expensive test. This is where a simple, cost-effective serum viscosity test comes in.

Serum viscosity is not affected by fibrinogen levels but is affected by antibody levels. Therefore, if a plasma and a serum viscosity analysis is performed on blood from a Covid-19 patient, drawn at the same time, it is possible to extrapolate meaningful clinical data by comparing the two results.

It is unusual to have reduced values of either plasma or serum viscosity.

Logically patients can have: -

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.

In conclusion these simple cost-effective tests could well be the way of leading the world out of the dilemma posed by SARS-CoV-2. At least until that elusive vaccine is available.

 

 

 

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Nov 13, 2020

Why blood viscosity testing could be an important key for Covid-19 treatment

Blood thickness is emerging as an important indicator of dangerous complications in Covid-19 patients, causing demand for the blood viscometers manufactured by Benson Viscometers in West Wales to sharply increase. We explore the reasons behind this.

 The battle against Covid-19 looks set to be a long one, and much remains to be understood about this virus. One significant recent development originated at Emory University in the USA and has dramatically increased demand for the instruments made by Benson Viscometers, a West Wales company that designs and manufactures a sophisticated clinical blood viscometer. Recognising that a second wave is likely, medical providers are now eager to equip themselves with testing equipment that is emerging as having a key role in directing the treatment of Covid-19 patients.

 The link between blood viscosity and Covid-19 began to emerge in June when doctors at Emory University noticed that many Covid-19 patients had unusual blood clotting that did not respond to the usual anti-clotting medication.

 “We were unsettled by the fact that some patients with severe Covid-19 had atypical blood clots, even when therapeutically anticoagulated,” says 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. 

 “Despite prescribing medications to prevent blood clots to Covid-19 patients, clotting still occurred, which is quite unusual,” says Maier. “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.” 

 This team went on to consider other causes of clot formation, like hyperviscosity, which can be detected by plasma viscosity (PV) testing. Hyperviscosity syndrome, where the high viscosity leads to dangerous sludging of the blood in the brain and other organs, produces viscosity levels similar to those seen in the sickest Covid-19 patients.

 “We found that the sickest patients with Covid-19 had the highest PV levels, more than twice normal levels,” says Maier. “We also found that patients with the highest viscosity levels were more likely to have a blood clot. We think that the inflammation caused by SARS-CoV-2 infection causes the hyperviscosity, which may contribute to blood clots in some patients.”

 The team is now exploring alternative treatment options based on this new finding. These include the use of therapeutic plasma exchange, which thins the blood and is a standard treatment for other conditions associated with hyperviscosity.

 “During plasma exchange the plasma of Covid-19 patients is replaced with donated plasma,” explains Maier. “This reduces the viscosity by normalizing 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.

 “Covid-19 is a unique disease. There is more going on with these atypical blood clots than we first realised. Hyperviscosity may be an important piece of the puzzle in linking inflammation to clotting.

 “We need larger studies to understand whether hyperviscosity is simply a marker of severe Covid-19 or actually contributing to blood clots in these patients,” she adds. “Nevertheless, we’re trying to determine any beneficial role of lowering the viscosity in these patients through a treatment called plasma exchange.”

 News of the potential significance of hyperviscosity in Covid-19 patients has been spreading. A paper in The Lancet on May 25th details Emory University’s findings, while an article in Newsweek on May 28th further explored this study and the links between PV and Covid-19. 

 In the UK, Addenbrookes Hospital is using Benson Viscometers’ equipment to explore how best to understand and treat Covid-19. They have been carrying out the 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 result. This is in line with what we would expect,” says Daniel Gleghorn, Senior Biomedical Scientist - Automation Lead, Clinical Haematology, Cambridge University Hospitals NHS Foundation Trust.

 “I believe the PV has potential as a useful marker in the diagnostic assessment of patients with suspected Covid-19 and for monitoring disease progression.”

 He adds that the PV test has some important advantages over other tests that are used to detect inflammation, including cost and availability.

 “From a laboratory management perspective, it is well documented that the PV provides a more useful indicator of infection, inflammation and malignancy than the traditional ESR,” he says. “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.

 “There is also the benefit of a less complicated and reliant supply chain for consumables and reagents. This has been significantly affected for other tests (CRP, procalcitonin and Interleukin-6) where this is not the case due to a worldwide increase in demand and the effects of lockdowns on distribution networks.”

 Meanwhile, Health Services Laboratories in London is also on the case. HSL is a partnership between the Australian company TDL (The Doctors Laboratory), UCLH (University College London Hospitals NHS Foundation Trust), The Royal Free London NHS Foundation Trust and North Middlesex University Hospital. 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, and is exploring the possibility that high inflammatory markers might indicate the need for alternative strategies for stroke prevention in these patients.

 “We are running PV now to monitor inflammatory status in the following patient groups: 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,” says Deepak Singh, Head of Department, Haematosis, at Health Service Laboratories. “This is to ensure anti-platelet drug therapy efficacy.

 “The aim is to get an overall insight on the reoccurrence of strokes despite patients being on anti-platelet medication and to identify the battery of tests available that can help in these cases.”

 They are not alone: laboratories all around the world are now exploring the role that measuring PV can play in monitoring the progression of Covid-19, helping to develop a more scientifically targeted treatment for patients and producing improved recovery outcomes. A growing number of long-standing experts in the field are backing this development.

 Paul Woods, a former pathology laboratory manager at Nobles Hospital in the Isle of Man, reports that PV testing is being used there: "Some laboratory tests are being utilised by the emergency department in relation to Covid-19 particularly d-dimer and ferritin,” he says.  “These tests are also being used to monitor patients who appear to be deteriorating and may be in need of more intensive care. The laboratory recently also facilitated PV availability 24/7 in relevant Covid-19 cases, which is notable, given it is not normally an out of hours test."

 The significance of these developments should not be underestimated. Gregory Sloop, Associate Professor of Pathology, Idaho, wrote in a recent article on Medium.com: “Regarding the unusual presentations of Covid-19, Yale School of Medicine cardiologist Harlan Krumholz, M.D. said ‘Our ignorance is profound’. Much of this mystery stems from ignoring blood viscosity. Because blood viscosity is inversely related to blood flow, elevated blood viscosity increases the risk of clotting and causes hypoxemia.” 

 Experts are also highlighting the reliability of the PV test. David Norcliffe, a recently retired biomedical scientist specialising in haematology and a much respected ambassador in this field, has been aware of the importance of PV measurement in many clinical conditions including inflammation, different types of infection, malignancies and many blood disorders for most of his 43 working years in the NHS. 

 “While there are alternative tests for inflammation and infection none of them surpass the accuracy, precision and suitability of PV for diagnosis and monitoring,” David says. “There are constantly new applications found for PV, serum viscosity and red cell deformability on an almost daily basis and none more so than in the current climate of battling Covid-19.  Recent research illustrates a significant change in some of these parameters in the immediate time leading up to symptoms developing which is potentially an exciting finding and might save the lives of many patients by early diagnosis and treatment.

 “Overall I believe the study of blood flow (Haemorheology) is of paramount importance in the diagnosis and monitoring of many disease processes and could potentially improve the lives of hundreds of thousands of patients in the future.  It also allows for a fresh look at long established diseases in times to come.”

 Explaining the significance of the PV test further, he highlights the fact that all tissues and organs are dependent on a good blood supply for their function and integrity.  Blood flow is dependent on three things: PV, haematocrit (the percentage of red cells in blood) and the degree of red cell flexibility. 

 “A small numerical change in any of these represents a significant clinical change,” he says. “Hence the method of measurement must demonstrate a high degree of accuracy (the degree of closeness to a fixed, known value) and precision (the degree of reproducibility or repeatability).  Only Benson Viscometers can do this to the level required and also has the advantage of using only a small amount of blood.”

 For Benson Viscometers, these developments have led to heightened interest in the clinical analysers the company has been making for over 20 years. Demand for viscosity testing has now risen so much in the light of Covid-19 that the company is about to take on additional premises in Haverfordwest in order to increase its production capabilities.

 The family-run company started life in 1999 and has established itself as the leader in the provision of clinical blood viscometers throughout the UK. The majority of the analysers have been installed in National Health Service (NHS) Pathology laboratories, but private laboratories located in Europe and the USA also use its equipment. Its blood viscometer analysers have the ability to provide fast, effective and accurate results and support compliance with ISO 15189.

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

 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.

 Besides the new discoveries around Covid-19, other serious conditions are associated with a high PV result. High PV is a known risk-factor for thrombosis and can be caused by increased levels of plasma proteins, such as fibrinogen or immunoglobulins.  PV results divide into a range of bands that can be of assistance to clinicians in interpreting the results. 

 Serum viscosity measures the fluid which is released during blood clotting and therefore does not contain the factors required for coagulation, of which fibrinogen is one. Therefore the main factor to affect serum viscosity is antibody concentration.

 In current practice whole blood viscosity measurements are time consuming and difficult to perform.  Many analysers require measurements at varying shear rates on the same sample. Fortunately in Covid-19 patients, the most valuable information is obtained from plasma and serum viscosity analysis.

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

 In an paper, 'The role of chronic hyperviscosity in vascular disease' written by Gregory Sloop, Ralph E. Holsworth, Jr, Joseph J Weidman and others, it has been recommended that blood viscosity should be measured routinely in medical practice.

The paper stated "cardiovascular disease is still the leading cause of deaths for both men and women worldwide. Many risk factors have been identified and current therapeutic efforts have been centered on addressing these risk factors. However, as of today, the role that blood viscosity plays in this disease has not yet received its due attention. Viscosity is a fundamental property of any fluid. It's important role in both normal individuals and patients afflicted with cardiovascular disease has been underestimated. Past and current research has reported the benefits in addressing this important factor; however, mainstream medicine has not appreciated or fully accepted this important measurement. With continued research and published, peer-reviewed studies pertaining to the importance of blood viscosity in cardiovascular diseases, this relationship will be recognized, appreciated and will no doubt reveal the positive aspects of hemorheology, which will save lives."

 While demand for its blood viscometers continues to rise, Benson Viscometers is also proud of its ability to design and develop new systems and is currently testing a device which is not associated with viscosity to increase its market base. The aim of the new coagulation profiling device is to reduce the time delay to commence correct blood component therapy.

 Benson Viscometers is developing a mobile coagulation profiler which profiles and plots the progression of the clotting of fresh whole blood in real time.  The instrument is being designed to enable it to be used at the scene of an accident in areas such as the roadside, at a major trauma incident and for military front-line use, next to the injured patient. The instrument will operate beside the patient in mobile scenarios such as ambulances, in air ambulances, and in static areas such as accident and emergency units, operating theatres, and obstetric units.

 Bernie Benson, who created Benson Viscometers, is pleased to see his equipment helping to shape the understanding of Covid-19 and the development of effective treatments.

 “Amidst the huge strain and challenges caused by this global pandemic, we are grateful that we are able to make a positive contribution to improving patient outcomes,” he says. “The PV test is highly valued and routinely used by many eminent UK and USA hospitals for a range of conditions. We believe that routine clinical viscosity testing will lead to a significant breakthrough in outcomes for critically ill patients, and not just those with Covid-19.

 "Looking to the future, there is clear potential for the viscosity test, and clinical viscometers to become mainstream tools in the treatment of Covid-19 patients."

 “Covid-19 is not going away, well at least not for the next few years,” says Gleghorn. “There is, however, a need for a diagnostic and prognostic testing strategy not just for the short term, but for many years ahead. If it can be proven that a PV can be used as part of a diagnostic algorithm, possibly as a positive predictive indicator for Covid-19 it may then form part of a recognised battery of tests for this purpose.

 “In addition, determining the prognostic value of PV will hopefully provide an aid to clinicians showing a potential improvement or deterioration in the patient’s condition. The clinicians can then act appropriately in a timely manner. PV at point of care for these patients may also be a possibility.”

 

 

 

 

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Nov 13, 2020

Plasma Viscosity in Covid-19

Covid-19, or SARS-COV-2, which emerged in late 2019, continues to spread around the world, infecting more than 4.5m people at time of writing, and leading to more than 300,000 deaths.   The disease presents a rapid learning challenge for everyone involved in battling with it.  Whilst widely regarded as primarily a respiratory disease, it is increasingly being recognised by doctors and scientists as being a systemic infection, which affects not only the respiratory tract, but also the central nervous system, muscular skeletal, renal, haematologic and hepatic systems. 

The haematalogic clinical manifestations of Covid-19 are receiving increasing attention, as the scientific and medical community work hard at trying to solve some of the many questions the outbreak poses.  For example, why is it that some patients have severe symptoms whilst others have relatively mild symptoms?  What is the pathology of the emerging phenomenon of the Kawasaki-like illness linked to Covid-19, which has coronary artery aneurysms as its main complication? (1)  Why do a substantial proportion of severe Covid-19 patients develop venous and arterial thromboembolic conditions, and what can we do to improve early recognition of these? (2) Haematological investigations are going to be critical to solving these and other emerging questions.  Many of the supporting answers could lie in plasma viscosity.

Plasma Viscosity Testing
 
Plasma viscosity testing is a sensitive index of plasma protein changes which result from inflammation or tissue damage.  The plasma viscosity test is well-established in many NHS hospitals, including some at the forefront of our fight against Covid-19, such as UCLH and St Thomas’ in London and Addenbrookes, Cambridge.  It is a highly accurate indicator of many conditions including any inflammatory disorder (e.g, infection, rheumatoid arthritis), tuberculosis, polymyalgia rheumatica/temporal arteritis. It is also used as a marker for subsequent adverse events in angina and stroke and peripheral occlusive vascular disease16.  Plasma viscosity is used as a screening test but, unlike some other indicators and inflammatory markers, it is not affected by haematocrit variations (e.g, anaemia or polycythaemia), or gender, patient age, exercise, pregnancy and age of sample.

Many clinicians recommend the plasma viscosity test for its sensitivity.  Other benefits of the test are that plasma viscosity becomes abnormal early in the disease, has a low incidence of false normal values, can be performed on a sample up to 7 days old, is stable, technically reproducible and standardised, and that relatively small changes are significant for any individual.

Covid-19, as with any infection, will cause an increase in the release of acute phase proteins into the circulation.  plasma viscosity could be a particularly useful way of measuring this as it is known to show a significant increase in a range of different types of infection, including viral and bacterial. 

Early Identification of Severely-Affected Patients
 
Benson Viscometers, global leaders in the clinical measurement of plasma viscosity, are currently exploring the possibility with partner laboratories of early identification of Covid-19 patients who subsequently go on to develop severe symptoms.  This is important because early intervention could increase the likelihood of early recovery. 

 A symptomatic or confirmed person with Covid-19 will probably have an increased plasma viscosity above the normal range.  The patient’s result is likely to continue rising if their condition deteriorates, until their immune response successfully has the infection under control.  A rising daily plasma viscosity may indicate a Covid-19 patient is developing severe symptoms and requires more intensive therapy, such as oxygen support in the form of CPAP or IPPV (ventilation).  Similarly, a fall or plateau of plasma viscosity results could be indicative that a patient is over the worst of the infection and that they therefore require a less intrusive approach.

 Identification of Recovered Patients
 
Whilst the patient is in recovery, the plasma viscosity result is likely to begin to fall.  However, paradoxically, most patients are likely still to have a positive antigen test.  It is proposed that the start of the reduction in viscosity, when measured on consecutive days, could be used as an indicative marker for patient recovery.  Hence the patient and their relatives could be informed potentially earlier than at present that there is an indication of recovery, thus reducing anxiety for clinicians and families. If a daily plasma viscosity monitoring routine is started as early as practical, a record of the disease’s progress will be available to aid clinicians in determining the most appropriate treatment.  With data analysis and experience, they will then be able to forecast and prepare for a worsening condition if the data shows a patient in a deteriorating situation.

 Plasma Therapy
 
The use of plasma therapy on Covid-19 patients is also an area of significant interest.  This experimental therapy involves transfusing the antibody-rich blood serum of recovered Covid-19 patients into people who are fighting the illness.  A recent study, co-authored by researchers at several institutions including Michigan State University, has shown that the treatment is safe.  Plasma viscosity measurement could be an important next step in establishing its effectiveness.

 

As one of the parameters that raise the plasma viscosity result is the concentration of antibodies in a person’s plasma, patients who have recovered from the virus but maintain a raised viscosity result may have high titre (antibody level) which would suggest they could be suitable donors for plasma pheresis to provide antibody therapy protection to other patients.

Research
 
The hypotheses about plasma viscosity are based on anecdotal evidence and need to be proven through clinical lab trials.  Bernie Benson, founder of Benson Viscometers, says “we are seeking to work with clinical and academic groups, potentially to form partnerships to undertake the required analysis.  If anyone is planning to undertake a study or trial, we would welcome discussions to progress this.  The plasma viscosity test could be specifically used as part of local Covid-19 screening blood work and also to monitor the intensity and progress of the virus episode in a patient, especially given most hospitalised Covid-19 patients are already having daily haematology and chemistry profiles carried out.” 

 Safe, Inexpensive and Precise
 
For obvious safety reasons laboratories are applying the principles of ‘closed vial sampling’ more rigidly now and as a result, any test on a Covid-19 patient that is under filled or requires the sample top to be removed, is generally refused unless in exceptional circumstances. The plasma viscosity analysis is carried out without removing the sample tube cap so is ideally suited to the current circumstances and will provide rapid and straight forward numerical results. There is one normal range for all ages and both sexes (1.5 to 1.72mPA.s) which is already well established and documented for over 50 years, meaning results interpretation is straight forward and there is no requirement to establish a normal range.

 Plasma viscosity is a safe and inexpensive test that is capable of a precise result with a high level of confidence within minutes of getting a blood sample to the hospital laboratory. All the NHS clinical viscometers in use are manufactured and supplied by a British company. They are already operational at this moment, programmed and linked via the NHS ‘LIMS’ (a Laboratory Information Management System), enabling hospitals to effectively manage samples and automatically communicate results and associated data. Therefore, obtaining results for a multi-centre trial is easy.

 Conclusion
 
The role of plasma viscosity in Covid-19 is an avenue which cannot be ignored.  In the battle against Covid-19, we need the shared knowledge and contributions of research, statistical analysis and “lessons learned” from a wide range of disciplines.  Haematology is increasingly emerging as a discipline with a crucial role to play.  The plasma viscosity test will play a significant part in that, as both an individual test, and as part of a routine blood work up panel. To facilitate this, there now needs to be as many plasma viscosity tests performed as possible to provide large volumes of meaningful data which can be evaluated and statistically analysed to assist with Covid-19 but also with any future pandemics. For any laboratories with a reduced routine workload volume, this is an opportune time to utilise available capacity and existing equipment to support finding the answers to Covid-19.

 

1328 words

 

 

References 

 1.      https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31129-6/fulltext
2.      https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30145-9/fulltext#.Xroex9wrZpI.linkedin
3.      Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Apr 10. doi: 10.1016/j.thromres.2020.04.013. [Epub ahead of print.] https://www.thrombosisresearch.com/article/S0049-3848(20)30120-1/pdf
4.https://www.practiceupdate.com/content/anticoagulant-treatment-is-associated-with-decreased-mortality-in-severe-covid-19-patients-with-coagulopathy/98435?trendmd-shared=0
5.      https://www.ncbi.nlm.nih.gov/pubmed/1105219

 

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Nov 13, 2020

Why a simple blood test could identify those most at risk of Covid-19 complications

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 patient’s 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 Maier’s 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.

 

 

 



 

 

 

https://www.bensonviscometers.com/

 

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Sep 23, 2020

The Welsh business at the forefront of the fight against COVID-19

“We’ve made fantastic progress, even during these challenging times of a global pandemic, thanks to Business Wales AGP.”

 The Welsh business at the forefront of the fight against COVID-19

How has support from Business Wales AGP helped your business?

We approached Landsker Business Solutions for help to obtain Business Wales AGP support to progress the development of an innovative, mobile blood coagulation measuring device. 

 The analyser helps healthcare providers determine what type of intervention a patient needs to secure normal clotting of their blood. 

 This minimises blood loss and avoids unnecessary transfusion of donor blood products. With the ability to be used in clinical environments such as ambulances, air ambulances, trauma centres and in frontline military situations, the instrument will revolutionise the quality of care provided to trauma patients. 

 This is a significant milestone for us and the growth of our international operations. 

 We’ve made fantastic progress, even during these challenging times, thanks to Business Wales AGP.

 Visit the Business Wales Accelerated Growth Programme website to see the full case study.

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Sep 16, 2020

Dundee biomedical scientist wins award for his writing on blood plasma viscosity testing

Chris Bell, a Dundee-based biomedical scientist has won the 2020 Bernie Benson Prize for his science writing in his essay which highlighted the emerging use of the plasma viscosity test in Covid-19 patients.

The Bernie Benson competition sought to promote the understanding and exploration of blood viscosity testing – an affordable and reliable test that is currently receiving a lot of interest due to its potential to identify Covid-19 patients who are at risk of fatal blood clots.

The competition was run by Bernie’s company, medical equipment manufacturer Benson Viscometers. This year it invited entrants to provide an essay or presentation discussing the uses of blood plasma viscosity testing for diagnosis, monitoring and screening.

Bernie Benson travelled to Dundee to present Chris with his prize – a Acer Chromebook 15.6” touchscreen laptop with 64gig SSD.

Bernie said: “It was an excellent bit of writing”. Chris highlighted the advantage of the plasma viscosity (PV) test in relation to Covid-19 but also referenced the long-standing benefits of PV, which have been recognised for many years. He said “I am very proud of being selected as the winner of this competition. I am also pleased for our laboratory, given all the hard work we’ve been doing this year through the pandemic.”

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Aug 3, 2020

Why Blood Viscosity Testing Could Be an Important Key for Covid-19

Blood thickness is emerging as an important indicator of dangerous complications in Covid-19 patients, causing demand for blood viscometers.

 August 3, 2020 — The battle against Covid-19 looks set to be a long one, and much remains to be understood about this virus. One significant recent development originated at Emory University in the USA and has dramatically increased demand for the instruments made by Benson Viscometers, a West Wales company that designs and manufactures a sophisticated clinical blood viscometer. Recognising that a second wave is likely, medical providers are now eager to equip themselves with testing equipment that is emerging as having a key role in directing the treatment of Covid-19 patients.

 The link between blood viscosity and Covid-19 began to emerge in June when doctors at Emory University noticed that many Covid-19 patients had unusual blood clotting that did not respond to the usual anti-clotting medication.

 “We were unsettled by the fact that some patients with severe Covid-19 had atypical blood clots, even when therapeutically anticoagulated,” says 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. 

 “Despite prescribing medications to prevent blood clots to Covid-19 patients, clotting still occurred, which is quite unusual,” says Maier. “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.” 

 This team went on to consider other causes of clot formation, like hyperviscosity, which can be detected by plasma viscosity (PV) testing. Hyperviscosity syndrome, where the high viscosity leads to dangerous sludging of the blood in the brain and other organs, produces viscosity levels similar to those seen in the sickest Covid-19 patients.

 “We found that the sickest patients with Covid-19 had the highest PV levels, more than twice normal levels,” says Maier. “We also found that patients with the highest viscosity levels were more likely to have a blood clot. We think that the inflammation caused by SARS-CoV-2 infection causes the hyperviscosity, which may contribute to blood clots in some patients.”

 The team is now exploring alternative treatment options based on this new finding. These include the use of therapeutic plasma exchange, which thins the blood and is a standard treatment for other conditions associated with hyperviscosity.

 “During plasma exchange the plasma of Covid-19 patients is replaced with donated plasma,” explains Maier. “This reduces the viscosity by normalizing 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.

 “Covid-19 is a unique disease. There is more going on with these atypical blood clots than we first realised. Hyperviscosity may be an important piece of the puzzle in linking inflammation to clotting.

 “We need larger studies to understand whether hyperviscosity is simply a marker of severe Covid-19 or actually contributing to blood clots in these patients,” she adds. “Nevertheless, we’re trying to determine any beneficial role of lowering the viscosity in these patients through a treatment called plasma exchange.”

 News of the potential significance of hyperviscosity in Covid-19 patients has been spreading. A paper in The Lancet on May 25th details Emory University’s findings, while an article in Newsweek on May 28th further explored this study and the links between PV and Covid-19. 

 In the UK, Addenbrookes Hospital is using Benson Viscometers’ equipment to explore how best to understand and treat Covid-19. They have been carrying out the 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 result. This is in line with what we would expect,” says Daniel Gleghorn, Senior Biomedical Scientist - Automation Lead, Clinical Haematology, Cambridge University Hospitals NHS Foundation Trust.

 “I believe the PV has potential as a useful marker in the diagnostic assessment of patients with suspected Covid-19 and for monitoring disease progression.”

 He adds that the PV test has some important advantages over other tests that are used to detect inflammation, including cost and availability.

 “From a laboratory management perspective, it is well documented that the PV provides a more useful indicator of infection, inflammation and malignancy than the traditional ESR,” he says. “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.

 “There is also the benefit of a less complicated and reliant supply chain for consumables and reagents. This has been significantly affected for other tests (CRP, procalcitonin and Interleukin-6) where this is not the case due to a worldwide increase in demand and the effects of lockdowns on distribution networks.”

 
Meanwhile, Health Services Laboratories in London is also on the case. HSL is a partnership between the Australian company TDL (The Doctors Laboratory), UCLH (University College London Hospitals NHS Foundation Trust), The Royal Free London NHS Foundation Trust and North Middlesex University Hospital. 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, and is exploring the possibility that high inflammatory markers might indicate the need for alternative strategies for stroke prevention in these patients.

 “We are running PV now to monitor inflammatory status in the following patient groups: 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,” says Deepak Singh, Head of Department, Haematosis, at Health Service Laboratories. “This is to ensure anti-platelet drug therapy efficacy.

 “The aim is to get an overall insight on the reoccurrence of strokes despite patients being on anti-platelet medication and to identify the battery of tests available that can help in these cases.”

 They are not alone: laboratories all around the world are now exploring the role that measuring PV can play in monitoring the progression of Covid-19, helping to develop a more scientifically targeted treatment for patients and producing improved recovery outcomes. A growing number of long-standing experts in the field are backing this development.

 Paul Woods, a former pathology laboratory manager at Nobles Hospital in the Isle of Man, reports that PV testing is being used there: "Some laboratory tests are being utilised by the emergency department in relation to Covid-19 particularly d-dimer and ferritin,” he says.  “These tests are also being used to monitor patients who appear to be deteriorating and may be in need of more intensive care. The laboratory recently also facilitated PV availability 24/7 in relevant Covid-19 cases, which is notable, given it is not normally an out of hours test."

 The significance of these developments should not be underestimated. Gregory Sloop, Associate Professor of Pathology, Idaho, wrote in a recent article on Medium.com: “Regarding the unusual presentations of Covid-19, Yale School of Medicine cardiologist Harlan Krumholz, M.D. said ‘Our ignorance is profound’. Much of this mystery stems from ignoring blood viscosity. Because blood viscosity is inversely related to blood flow, elevated blood viscosity increases the risk of clotting and causes hypoxemia.” 

 Experts are also highlighting the reliability of the PV test. David Norcliffe, a recently retired biomedical scientist specialising in haematology and a much respected ambassador in this field, has been aware of the importance of PV measurement in many clinical conditions including inflammation, different types of infection, malignancies and many blood disorders for most of his 43 working years in the NHS. 

 “While there are alternative tests for inflammation and infection none of them surpass the accuracy, precision and suitability of PV for diagnosis and monitoring,” David says. “There are constantly new applications found for PV, serum viscosity and red cell deformability on an almost daily basis and none more so than in the current climate of battling Covid-19.  Recent research illustrates a significant change in some of these parameters in the immediate time leading up to symptoms developing which is potentially an exciting finding and might save the lives of many patients by early diagnosis and treatment.

 “Overall I believe the study of blood flow (Haemorheology) is of paramount importance in the diagnosis and monitoring of many disease processes and could potentially improve the lives of hundreds of thousands of patients in the future.  It also allows for a fresh look at long established diseases in times to come.”

 Explaining the significance of the PV test further, he highlights the fact that all tissues and organs are dependent on a good blood supply for their function and integrity.  Blood flow is dependent on three things: PV, haematocrit (the percentage of red cells in blood) and the degree of red cell flexibility. 

 “A small numerical change in any of these represents a significant clinical change,” he says. “Hence the method of measurement must demonstrate a high degree of accuracy (the degree of closeness to a fixed, known value) and precision (the degree of reproducibility or repeatability).  Only Benson Viscometers can do this to the level required and also has the advantage of using only a small amount of blood.”

 For Benson Viscometers, these developments have led to heightened interest in the clinical analysers the company has been making for over 20 years. Demand for viscosity testing has now risen so much in the light of Covid-19 that the company is about to take on additional premises in Haverfordwest in order to increase its production capabilities.

 The family-run company started life in 1999 and has established itself as the leader in the provision of clinical blood viscometers throughout the UK. The majority of the analysers have been installed in National Health Service (NHS) Pathology laboratories, but private laboratories located in Europe and the USA also use its equipment. Its blood viscometer analysers have the ability to provide fast, effective and accurate results and support compliance with ISO 15189.

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

 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.

 Besides the new discoveries around Covid-19, other serious conditions are associated with a high PV result. High PV is a known risk-factor for thrombosis and can be caused by increased levels of plasma proteins, such as fibrinogen or immunoglobulins.  PV results divide into a range of bands that can be of assistance to clinicians in interpreting the results. 

 Serum viscosity measures the fluid which is released during blood clotting and therefore does not contain the factors required for coagulation, of which fibrinogen is one. Therefore the main factor to affect serum viscosity is antibody concentration.

 In current practice whole blood viscosity measurements are time consuming and difficult to perform.  Many analysers require measurements at varying shear rates on the same sample. Fortunately in Covid-19 patients, the most valuable information is obtained from plasma and serum viscosity analysis.

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

 In an paper, 'The role of chronic hyperviscosity in vascular disease' written by Gregory Sloop, Ralph E. Holsworth, Jr, Joseph J Weidman and others, it has been recommended that blood viscosity should be measured routinely in medical practice.

The paper stated "cardiovascular disease is still the leading cause of deaths for both men and women worldwide. Many risk factors have been identified and current therapeutic efforts have been centered on addressing these risk factors. However, as of today, the role that blood viscosity plays in this disease has not yet received its due attention. Viscosity is a fundamental property of any fluid. It's important role in both normal individuals and patients afflicted with cardiovascular disease has been underestimated. Past and current research has reported the benefits in addressing this important factor; however, mainstream medicine has not appreciated or fully accepted this important measurement. With continued research and published, peer-reviewed studies pertaining to the importance of blood viscosity in cardiovascular diseases, this relationship will be recognized, appreciated and will no doubt reveal the positive aspects of hemorheology, which will save lives."

 While demand for its blood viscometers continues to rise, Benson Viscometers is also proud of its ability to design and develop new systems and is currently testing a device which is not associated with viscosity to increase its market base. The aim of the new coagulation profiling device is to reduce the time delay to commence correct blood component therapy.

 Benson Viscometers is developing a mobile coagulation profiler which profiles and plots the progression of the clotting of fresh whole blood in real time.  The instrument is being designed to enable it to be used at the scene of an accident in areas such as the roadside, at a major trauma incident and for military front-line use, next to the injured patient. The instrument will operate beside the patient in mobile scenarios such as ambulances, in air ambulances, and in static areas such as accident and emergency units, operating theatres, and obstetric units.

 Bernie Benson, who created Benson Viscometers, is pleased to see his equipment helping to shape the understanding of Covid-19 and the development of effective treatments.

 “Amidst the huge strain and challenges caused by this global pandemic, we are grateful that we are able to make a positive contribution to improving patient outcomes,” he says. “The PV test is highly valued and routinely used by many eminent UK and USA hospitals for a range of conditions. We believe that routine clinical viscosity testing will lead to a significant breakthrough in outcomes for critically ill patients, and not just those with Covid-19.

 "Looking to the future, there is clear potential for the viscosity test, and clinical viscometers to become mainstream tools in the treatment of Covid-19 patients."

 “Covid-19 is not going away, well at least not for the next few years,” says Gleghorn. “There is, however, a need for a diagnostic and prognostic testing strategy not just for the short term, but for many years ahead. If it can be proven that a PV can be used as part of a diagnostic algorithm, possibly as a positive predictive indicator for Covid-19 it may then form part of a recognised battery of tests for this purpose.

 “In addition, determining the prognostic value of PV will hopefully provide an aid to clinicians showing a potential improvement or deterioration in the patient’s condition. The clinicians can then act appropriately in a timely manner. PV at point of care for these patients may also be a possibility.”

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Jul 29, 2020

Jul 13, 2019

Plasma Viscosity Has a Role in the Diagnosis of Prosthetic Joint Infection After Total Knee Arthroplasty

Abstract

Background


The diagnosis of prosthetic joint infection (PJI) is challenging because no single test has consistently demonstrated an adequate discriminative potential. The combination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with adequate thresholds is well established. This study sought to investigate the role of plasma viscosity (PV) in the diagnosis of PJI following painful total knee arthroplasty.

Methods

The medical notes, and hematological and microbiology results of 310 patients who underwent revision for a painful total knee arthroplasty were evaluated. Infection was confirmed using Musculoskeletal Infection Society criteria in 102 patients (32.9%), whereas 208 patients (67.1%) were classified as noninfected. Serum investigations including ESR, CRP, and PV were analyzed using receiver observer curves and optimal cutoff points identified.

Results

There was a strong correlation between PV and both ESR and CRP. The area under curve was 0.814 for PV and 0.812 for ESR. Statistical analysis showed noninferiority of PV as compared to ESR in diagnosing PJI. A PV value of ≥ 1.81 mPa.s. had the best efficiency of 82.1%. Combining a CRP ≥ 13.5 mg/L with a PV ≥ 1.81 mPa.s. in a serial test approach yielded the highest specificity of 97.9% and positive likelihood ratio of 22.8. Sensitivity was 47.9% and a negative likelihood ratio of 0.53.

Conclusion

PV is noninferior to ESR in diagnosing PJI. Its use is justified in clinical practice. It is cheaper, quicker, more efficient, and not influenced by hematocrit levels or medication. In this cohort, a PV value ≥ 1.81 mPa.s. would be an adequate cutoff to diagnose PJI in combination with CRP ≥ 13.5 mg/L.

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May 20, 2019

Plasma Viscosity and NLR in Young Subjects with Myocardial Infarction: Evaluation at the Initial Stage and at 3 and 12 Months

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Oct 17, 2016

Plasma and blood viscosity in the prediction of cardiovascular disease and mortality in the Scottish Heart Health Extended Cohort Study

Abstract
Background There is increasing evidence that blood viscosity and its major determinants (haematocrit and plasma viscosity) are associated with increased risks of cardiovascular disease (CVD) and premature mortality; however, their predictive value for CVD and mortality is not clear. Methods We prospectively assessed the added predictive value of plasma viscosity and whole blood viscosity and haematocrit in 3386 men and women aged 30-74 years participating in the Scottish Heart Health Extended Cohort study. Results Over a median follow-up of 17 years, 819 CVD events and 778 deaths were recorded. Hazard ratios (95% confidence intervals) for a 1 SD increase in plasma viscosity, adjusted for major CVD risk factors, were 1.12 (1.04-1.20) for CVD and 1.20 (1.12-1.29) for mortality. These remained significant after further adjustment for plasma fibrinogen: 1.09 (1.01-1.18) and 1.13 (1.04-1.22). The corresponding results for blood viscosity were 0.99 (0.90, 1.09) for CVD, and 1.11 (1.01, 1.22) for total mortality after adjustment for major CVD risk factors; and 0.97 (0.88, 1.08) and 1.06 (0.96, 1.18) after further adjustment for fibrinogen. Haematocrit showed similar associations to blood viscosity. When added to classical CVD risk factors, plasma viscosity improved the discrimination of CVD and mortality by 2.4% (0.7-4.4%) and 4.1% (2.0-6.5%). Conclusions Although plasma and blood viscosity may have a role in the pathogenesis of CVD and mortality, much of their association with CVD and mortality is due to the mutual effects of major CVD risk factors. However, plasma viscosity adds to the discrimination of CVD and mortality and might be considered for inclusion in multivariable risk scores.

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Feb 1, 2012

Erythrocyte sedimentation rate: the extinction of a dinosaur laboratory test?

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Feb 10, 2010

About us

Company details

Benson Viscometers is a British company specialising in the design, development and manufacture of high-quality clinical viscometers and blood measuring equipment. At Benson Viscometers we believe in engineering excellence, technical innovation and quality of service.

We are proud that without any exception every member of the Benson Viscometers team personally “cares” about our responsibility to give an accomplished service in every aspect of our operation.

Established in 1999, our family-run company has established itself as the leader in the provision of clinical viscometers throughout the UK, Europe, and the USA.  

Following findings that blood viscosity could be an important pointer for identifying the Covid-19 patients who are most at risk and will require intense medical intervention, some of the largest and most respected healthcare providers in the US are among those that have purchased our clinical analysers.

We are extremely proud of our ISO 9001:2015 certification and are currently working towards our ISO 13485:2016 accreditation.

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Company information as a PDF file