Erythrocyte Sedimentation Rate
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Journal of Pre-Clinical and Clinical Research, 2011, Vol 5, No 2, 50-55 www.jpccr.eu REVIEW Erythrocyte sedimentation rate – an old marker with new applications Krzysztof Bochen, Anna Krasowska, Sylwia Milaniuk, Monika Kulczyńska, Andrzej Prystupa, Grzegorz Dzida Department of Internal Medicine, Medical University, Lublin, Poland Abstract Erythrocyte sedimentation rate (ESR) is an inexpensive and simple test for evaluating the infl ammatory or acute response. The ESR is a useful test in clinical practice as an indicator of infl ammation, infection, trauma or malignant disease. The ESR can also be an important prognostic factor in non-infl ammatory conditions, such as coronary heart disease, stroke, heart failure and prostate cancer. There are several methods for measuring the ESR, but the International Committee on Standarization in Hematology Reference Procedure accepts the Westergren method developed in the early 20th century. The aim of this work is to describe and evaluate the possible application of the ESR in modern clinical practice. In conclusion, the ESR evaluation, as a cheap method, may be a good alternative to newer and more expensive methods like C-reactive protein (CRP) determination. Key words erythrocyte sedimentation rate, C-reactive protein, infl ammation, rheumatic diseases, coronary heart disease, cancer INTRODUCTION or setting of a vertical column of erythrocytes within 1 h when held vibration free, and at room temperature [3]. Blood Erythrocyte sedimentation rate (ESR) is an inexpensive samples can be stored for up to 24 h at 4ºC. Venous blood with and simple test for evaluating the infl ammatory or acute anticoagulant (ethylenediaminetetraacetic acid – EDTA) is response. It was discovered by the Polish physician Edmund diluted 4:1 with sodium citrate and placed in a 200-mm glass Biernacki in 1897, but his discovery remained unknown for tube with a 2.5-mm internal diameter. At the end of 1 h, many years. Th e test was rediscovered and introduced to the the distance from the meniscus to the top of the column of scientifi c world in 1918 by the Swedish heamatologist and erythrocytes is recorded as the ESR in units of millimetres pathologist Robert Fahraeus who initially used the ESR as a per hour [3]. Erythrocyte aggregation is aff ected by 2 major pregnancy test [1]. Th e ESR is the most widely used laboratory factors: red cell surface charges and frictional forces around measure of disease activity in clinical medicine and still the red cell. Th e erythrocytes normally have negative charges remains a useful tool for monitoring infl ammatory diseases, and repel each other [6]. High molecular weight proteins in particular, rheumatoid arthritis [1]. Normal values of increase viscosity and favour rouleaux formation, and thus ESR depends on age and gender, and present themselves as would raise the ESR. Fibrinogen, the most abundant acute follows: phase reactant, has the greatest eff ect on the elevation of ESR • 12-17 mm/hr for infants < 6 months; in comparison to other acute phase proteins [7]. Paraproteins • 15 mm/hr or less for men < 50 years old; (positively charged molecules), when abundantly present – as • 20 mm/hr or less for men > 50 years old; in multiple myeloma or Waldenstrom macroglobulinemia – • 20 mm/hr or less for women < 50 years old; will increase the ESR levels by enhancing rouleaux formation • 30 mm/hr or less for women > 50 years old [2]. and elevating plasma viscosity[2, 7]. For this reason, plasma ESR values in healthy volunteers increase with age, and a viscosity measurement correlates with the ESR, but it is not as formula for calculating the maximal normal ESR at any age reliable as that of ESR since it is marginally aff ected by short- has been proposed [2]. Th e ESR value increases by 0.85 mm/h term changes in acute phase responses [2]. In vitro studies for each 5-year increase in age. Th is may be caused by elevated have shown that aft er isolation of erythrocytes from healthy levels of fi brinogen or higher occult disease prevalence in the volunteers, the ESR increased when albumin was added to a elderly [3]. But the highest normal ESR values appear to be mixture of fi brinogen and immunoglobulin. However, in the among people aged 65-74 years [4]. Th e elevated ESR increases same system and in hypoalbuminemic plasma, the addition of the probability of disease at any age [2]; however, physicians albumin decreased the ESR. Th erefore, in clinical situations should remember that in many patients no cause will be in which the albumin is normal, the ESR will only be aff ected found for an elevated ESR. Th e Internatinal Committee for by the level of acute phase reactants such as fi brinogen, Standarization in Hematology (ICSH) recommends the use whereas in hypoalbuminemic infl ammatory states the ESR of the Westergren method to measure the ESR [5]. Th e ESR may be more elevated than if the serum albumin was normal refl ects red blood cell aggregation and is the measured fall [8]. Extremely elevated ESR (value exceeding 100 mm/hr) is strongly connected with serious underlying diseases such as collagen vascular diseases, metastatic tumours or severe Corresponding author: Krzysztof Bochen, Departament of Internal Medicine, Medical University, Lublin, Poland. Staszica 16, 20-081 Lublin, Poland. infections [9]. In a study of 1,006 outpatients, the researchers E-mail: [email protected] found 42 cases with ESR > 100 mm/hr, and 37 with an ESR Received: 20 May 2011; accepted: 15 September 2011 between 75-99 mm/h. Th ere was an identifi able cause in 90% Journal of Pre-Clinical and Clinical Research, 2011, Vol 5, No 2 51 Krzysztof Bochen, Anna Krasowska, Sylwia Milaniuk, Monika Kulczyńska, Andrzej Prystupa, Grzegorz Dzida. Erythrocyte sedimentation rate – an old marker… of the former compared with 54% of those with the more to observe disease activity and to predict how well someone moderate rise [10]. is responding to treatment. ESR is not a perfect test because In a study with patients of ESR > 100 mm/h infections were it is infl uenced by various factors, such as age, gender and found to be t he most f requent ly associated diseases (35%), whi le anemia [13]. Th erefore, CRP is a test more sensitive to changes malignant diseases accounted for only 15% of the patients in the disease activity than ESR. CRP refl ects immediate [11]. Other causes of increased ESR are anemia, macrocytosis, changes and is not infl uenced by the same factors. Th e levels increased number of high molecular weight proteins in the of CRP correlate stronger with treatment and radiographic blood, low hematocrit, hypercholesterolemia, nephrotic progression than ESR. High levels of CRP in the early stage syndrome, severe liver injury, pregnancy and thyreoiditis of RA are noticed in patients with a worse prognosis and the [12]. On the other hand, conditions like hypofi brynogenemia, existence of progressive RA. High CRP and ESR levels are hypogammaglobulinemia, polycythemia, microcytosis, concomitant with raised levels of rheumatoid factor (RF) or hemolytic anemia, hemoglobinopathies, heart failure, anti-cyclic citrulinated peptide (anti-CCP). Finally, CRP is allergic diseases and anti-infl ammatory drugs can reduce a direct measure of the acute-phase response, and therefore the ESR value [13]. more precisely refl ects RA activity. It might be more useful Despite all these drawbacks, the ESR still plays an important in clinical practice. Studies have shown that high CRP and role in the diagnosis and follow-up of rheumatoid arthritis high ESR levels are usually observed in groups of patients with and temporal artheritis. ESR has also been reported to be of the worst clinical status. What is more, the following results clinical signifi cance in sick le cell disease, osteomyelitis, stroke, indicate improved clinical status, in ascending order: low coronary artery disease and prostate cancer. Th erefore, the ESR/ high CRP, low CRP/ high ESR, low CRP/ low ESR. Th e ESR is important in the diagnosis of infl ammatory conditions studies show that ESR can be a better choice for initial follow- and in the prognosis of non-infl ammatory conditions [14]. up, expecially for patients with early RA. However, it should Th e ESR should serve only as a guide and not as a screen, not be forgotten that the initial level of ESR does not correlate and only in symptomatic patients [6]. Current studies suggest with the presence of anty-cyclic citrullinated peptide [13]. Th e that the ESR when elevated remains high until the primary ESR and CRP results are a part of rheumatoid disease activity infl ammatory process is resolved [15]. scales [13]. Th ere are a few contemporary scales available: Recently, researchers have conducted several studies which the Disease Activity Score (DAS), Disease Activity Score 28 illustrate that the ESR may have more uses in clinical practice (DAS 28), Simplifi ed Disease Activity Index (SDAI), and the than expected. Despite its comparatively low sensitivity and Clinical Disease Activity Index ( CDAI). Th e DAS and DAS specifi city in monitoring disease activity, the simplicity to 28 scales include ESR, the SDAI scale contains CRP, whereas perform and the low cost make ESR an attractive alternative the CDAI has none of the APR. Th e major scoring system for to newer methods, e.g. CRP-determination in daily clinical evaluating disease activity in patients with RA is the DAS 28 practice. Th e introduction of automated ESR instruments can scale [17], founded on 28 tender and swollen joints, the health improve the quality control, reduce the sample handling risk, assessment of a patient, a visual analog scale (VAS) and ESR. and improve the speed of result availability [16].