BLOOD SCIENCES


at presentation and during its progress. There are no standard techniques for measuring and reporting CRP. It is commonly measured by immunoassay, though other techniques are sometimes used. The changes seen during acute inflammation can increase the value a hundredfold and each method must be able to encompass this, hence sensitivity is not always at the same level as some other metabolic assays. Furthermore, CRP increases with the age7


of the patient,


thus affecting the baseline and making interpretation challenging. CRP is a non-glycosylated protein, but Pathak and Agarwal (2019)8


described


different glycosylated forms in certain pathological conditions. However, the measurement of this single acute phase protein brings considerable limitations due to its isolated narrow base. Most notably, baseline levels can be influenced by a patient’s age, gender, smoking, body weight,9


lipid levels, and blood


pressure, while evidence also indicates that hormone replacement therapy (HRT) will have a profound influence on CRP which can produce higher incorrect results.10


in rheumatoid arthritis patients due to the heterogeneity11


A variety of point-of-care CRP assays are available and can be used in emergency care, as well as being suitable for outreach or satellite laboratories.


was standardised by Dr A Westergren, who was a founding member of the expert panel of International Committee for Standardisation in Haematology (ICSH); being published in 1973.18 The ESR test process mechanism is triphasic, producing a sigmoid curve, with each phase varying in length between patients. The three phases are: aggregation, sedimentation and packing of the red blood cells (alternatively this process is known as lag, log and syneresis). The ESR result is analysed and recorded after one hour on the assumption that the third phase is complete.


The traditional Westergren test


requires an EDTA anticoagulated sample, less than four hours old.19


An aliquot of


Also, variable results (the variability of


the intervention effects being evaluated in different studies) and with method variation. It is also known that females have a higher CRP titre than males and a concentration hook effect can exist in particularly high levels, thus introducing the possibility of erroneous quantitation.12 Certainly, any or all of these could explain some, previous reports that CRP does not always increase in viral infections.13


Hence


CRP results obtained when differentiating between viral and bacterial infections should be interpreted with caution. Developments have been made in CRP applications with small but significant changes being recognised as a possible cardiovascular risk factor in otherwise healthy, asymptomatic individuals. Hence high-sensitive assays (hs-CRP) have since been developed using immunonephelometry or immunoturbidity, which mostly focus on concentrations at or below the stated reference range, but are both more expensive than standard CRP assays and less commonly used. Furthermore, hs-CRP assays should not be used in the presence of other physiological inflammation, limiting the reliable use of hs-CRP, especially when diagnosing cardiovascular risks. Point-of-care (POC) CRP assays can be used in emergency care for possible detection of inflammation. This can be a useful guide and is also suitable for outreach or satellite laboratories. It has


also been reported that a CRP to albumin ratio of less than 32 has a negative predictive value of up to 89% for ruling out sepsis14


but the numerous influences


on the baseline must be considered in its interpretation. Normal reference ranges for CRP vary with the technique used and other factors but typically are usually approximately 3-10 mg/L.15


Health


care professionals and clinicians are still not in an agreement for an international numerical standard for a definitive normal range and abnormal range of CRP results. Perhaps this is due to the wide range of results produced by the many different manufacturers of CRP analysers and the varying analytical testing methods.


Erythrocyte sedimentation rate


The ESR is almost certainly the oldest laboratory blood test still in use; being first described over 100 years ago.16


It is


based on the principle of determining the rate of red cell (haematocrit) sedimentation falling through plasma under the influence of gravity, in a diluted stationary sample measured over one hour.17


An increase above the reference range may be an indicator of a disease process. It is influenced by the albumin/ globulin (AG) ratio, particularly fibrinogen. Although variations of the original technique had been used since 1921, it


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this sample is then diluted with trisodium citrate to reduce the zeta potential of the red cells, using a ratio of four parts blood to one part sodium citrate. This is gently mixed and transferred into a plugged, graduated tube measuring 200mm length and 2.5mm internal diameter. Then the tube is left to stand vertically away from direct sunlight, vibration, and from any form of movement, which are known as serious interfering factors in the process. The result is where the demarcation zone between plasma and red cells occurs and is reported in millimetre (mm) in one hour. However, due to variations in the length of each phase between patients, it is not uncommon for ‘streaming’ to occur. This is where the third phase is incomplete and a hazy, and unclear line of demarcation is seen, often occupying up to 20 mm of the graduated tube, thus making an accurate and clear results which is subjective and difficult to achieve. In the author’s experience this occurs in approximately 10% of ESR tests. There is a plethora of information about the numerous limitations of the ESR test, one of which is the dependence on the haematocrit, which gives rise to the different reference ranges for males, pre- and post-menopausal females. Drawbacks with ESR test includes the unphysiological nature of the test, the age of the sample prior to testing, the patients age, use of medication (particularly aspirin and steroids which can often distort a high result towards normal). External interfering factors which could affect the test results include temperature variations and any movement in the test environment. Most importantly the ESR test does not have realistic quality control and quality assurance materials to validate the test carried out. The


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