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Benson Viscometers Ltd SAMPLE LETTER 2012

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Hospital Address

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FAO Practice Medical Staff

Dear Colleagues

The Haematology Department is upgrading its service. This includes changing one of its tests frequently requested by general practitioners.

ESR will be replaced by the Plasma Viscosity test (PV). PV analysis removes some of the non-clinical variables associated with the ESR and therefore gives an improved result for diagnosis and monitoring of patients with chronic inflammatory disease. PV analysis is undertaken from the routine EDTA (purple top) full blood count tube, so no new or additional tube is required.

With the exception of clinical trials or specific patient testing, the laboratory will cease to use ESR tests from (date).

Apart from small stocks, any outstanding ESR tubes should be returned to the laboratory.

Enclosed are some general guidelines on the clinical use of PV along with a comparison to ESR results in detecting and monitoring chronic disease.

If having read the document you have any specific questions; please contact me directly on the above telephone number or by e-mail.

Yours sincerely

. Enc: Benson Viscometers Ltd SAMPLE LETTER 2012

PROPOSAL TO REPLACE ESR WITH PLASMA VISCOSITY

Background

Both plasma viscosity and ESR are used to monitor the acute phase response to “screen” for the presence of infection or inflammation and to monitor “disease activity” but there are significant differences between each test.

The Haematology Laboratory has reviewed its repertoire of tests and proposes to replace ESR measurements with measurements of plasma viscosity (PV). The case for change, both from a clinical and technical aspect, is made below.

Sample Requirements

A standard FBC sample (EDTA) is required for PV measurement. FBC and PV can be carried out on the same sample; no additional sample is required. PV is stable at room temperature for up to 1 week post sampling.

Interpretation of Results

PV range PV range (mPa.s.) (mPa.s.) Comments

25ºC 37ºC

Normal 1.40-1.75 1.05 - 1.30 Range

Low Found in infants under 3 years old and patients < 1.40 < 1.05 Results with low immunoglobulin or fibrinogen levels.

Chronic disorders e.g. infection, malignancy, High 1.75 - 2.00 1.30 - 1.46 vascular disease. Autoimmune such as rheumatic Results diseases.

Very High Suggestive of myeloma. IgG-paraproteins. High 2.01 - 3.00 1.47 - 2.18 Results concentration of asymmetric paraproteins

Extremely Suggestive of Waldenstrom's High >3.00 > 2.18 macroglobulinaemia. Results Grossly raised IgM-paraproteins.

Physiological Factors Influencing Plasma Viscosity

Age (after 3 years), gender, and diurnal rhythms have no effect on PV. Throughout life serial PV measurements in a healthy individual vary as little as 0.05 mPa.s. The only physiological factor that has a significant and consistent effect on PV is pregnancy. PV remains normal in the first two trimesters and gradually rises to around 1.80 mPa.s in the final trimester.

Small variations in PV may be clinically significant. Benson Viscometers Ltd SAMPLE LETTER 2012 Plasma Viscosity in Disease

 Acute phase response

As a result of the acute phase response many plasma proteins including fibrinogen and immunoglobulins are increased and this is reflected in a rise in PV. This response occurs within 2-24 hours.

 Chronic inflammatory diseases

Like the ESR, PV cannot diagnose any condition. However, when taken in conjunction with a clinical assessment a result in the range of 1.75 – 2.00 mPa.s can give a good indication of an underlying problem. ESRs and PVs are affected by different factors and are not always equivalent (see Tables). Studies have shown PV to be equal or superior to the ESR in monitoring of patients with rheumatoid arthritis and in the diagnosis of temporal arteritis. While anaemia and the age of the sample can affect the ESR with no change in the underlying condition, serial PV assessments will quite accurately reflect the progress of the condition as they are not influenced by these factors.

 Malignant disease

Early stage malignancy can be associated with a normal PV. With more advanced disease there is often a moderate rise in PV.

 Paraproteinaemias

This group of disorders can be associated with markedly raised PVs and such patients may display symptoms of hyperviscosity (confusion, visual disturbance, epistaxis, difficulty breathing, renal impairment). In general, IgM paraproteins are associated with much higher PVs than IgG and IgA paraproteins, but this cannot be assumed or inferred because some IgG and IgA molecules polymerize and lead to very high PVs.

NB: a normal PV, just the same as a normal ESR, does not exclude a diagnosis of light chain only or non-secretary myeloma.

 Severely ill patients

In severely ill patients (e.g. in intensive care) impaired synthesis and/or increased degradation of plasma proteins may lead to a fall in PV. This should not be taken as an indication of an improvement in the patient’s underlying condition in this situation. Benson Viscometers Ltd SAMPLE LETTER 2012

Comparison of PV and ESR: clinical aspects

Plasma viscosity ESR

Normal range the same for both sexes Normal range different for both sexes

Unaffected by physiological stimuli Influenced by age and haematocrit (except in pregnancy) (Red cell concentration)

Increased result due to change in protein No exact cause can be stated for increase in ESR concentration (Changes in Red cell shape/concentration and (mainly fibrinogen and/or globulins) protein changes)

Abnormal results detected earlier Abnormal results detected later

Low incidence of false negative results High incidence of false negative results

Serial tests in an individual responding to therapy ESR results show irregular peaks and troughs would show a fall in PV on a continuous curve without clinical explanation

High dose steroids do not normalise the PV. High dose steroids will return ESR to normal. (Inflammation must be reduced) (Underlying disease may not be improved)

Salicylates can lower the ESR result without Salicylates have no effect on PV improving the underlying condition of the patient

Polycythaemia does not interfere with Haematocrit >50% will produce a normal ESR measurements irrespective of the underlying disease

Results in myeloma and macroglobulinaemia are ESR cannot distinguish between protein characteristic and can be diagnostic abnormalities and inflammatory conditions

Comparison of PV and ESR: technical aspects

Plasma viscosity ESR Must be analysed within 4 hours of sampling Unaffected by time-induced deterioration and can unless EDTA sample, which has a 24 hour time be analysed up to 1 week post sampling limit Unaffected by anaemia Affected by anaemia Variations in red cell size and shape have no Red cell size and shape variations affect the rate effect of sedimentation All results are universally comparable. Results not universally comparable due to different Calibration using fully traceable, CE marked anticoagulants, tubes and timing methods. reagents External Independent Quality Control is available (Central Quality Assurance Scheme QEH. No Independent Quality Control possible. Birmingham UK.) Time factor: from receipt of sample, centrifugation Time factor: from receipt of sample, setting up and and testing takes 10 minutes if lab is notified in reading of result takes 65 minutes advance Benson Viscometers Ltd SAMPLE LETTER 2012

REFERENCES

1. G. D. O. Lowe. Should Plasma Viscosity Replace the ESR? : British Journal Of Haematology, 1994; 86, 6-11.

2. Orrell R W & Johnson M H (1993). Plasma viscosity and the diagnosis of giant cell arteritis. Br. J. Clin. Pract. 47(2):71-2

3. Gudmundsson M, E. Nordborg, B-A, Bengtsson, A, Bjelle. Plasma Viscosity in Giant Cell Arteritis as a Predictor of Disease Activity: Annals of the Rheumatic Diseases 1993; 52: 104-109.

4. Gudmundsson M & Bjelle A (1995). Plasma viscosity in the monitoring of therapy in rheumatoid arthritis patients. Scand. J. Rheumatol. 24(4):219-24.

5. International Committee for Standardization in Haematology (Expert panel on Rheology). Guidelines on selection of laboratory tests for monitoring the acute phase response: Journal of Clinical Pathology, 1988; 41: 1203-1212

6. T. Ng. Erythrocyte Sedimentation Rate, Plasma Viscosity and C-Reactive Protein in clinical Practice: British Journal of Hospital Medicine 1997; 58: 521-523.

7. H. A. Bird, W. Esselinckx, A. S. Dixon, et al. An Evaluation of Criteria for Polymyalgia Rheumatica: Annals of the Rheumatic Diseases 1979; 38: 434-439.

8. G. P. H. Brittain, G. G. Mcilwaine, J. A. Bell, J. M. Gibson. Plasma Viscosity or Erythrocyte Sedimentation Rate in the Diagnosis of Giant Cell Arteritis: British Journal of Ophthalmology 1991; 75: 656-659.

9. G. D. O. Lowe. Blood Rheology, Haemostasis and vascular disease: Haemostsis and Thrombosis ,3rd edition (edited by A. L. Bloom, C. D. Forbes, D. P. Thomas and E. G. D. Tuddenham); 1169-1188. Caryl Churchill Livingstone Edinburgh.

10. Paulus H E et al. (1999). Equivalence of the acute phase reactants C-reactive protein, plasma viscosity, and Westergren erythrocyte sedimentation rate when used to calculate American College of Rheumatology 20% improvement criteria or the disease activity Score in patients with early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists. J.Rheumatol. 26(11):2324-31.

11. Gertz M. A. and Kyle R. A.: 1995 Hyperviscosity Syndrome. Journal of Intensive Care Medicine 10 128-141.