Erythrocyte Sedimentation Rate (ESR)

Background

ESR or the erythrocyte sedimentation rate is a time honored laboratory method for determining the acute phase response to inflammation.

OUTLINE

Reference Methods

Clinical Utility

Interfering Diseases or Substances that Alter Levels

Commonly Used Terms

Internet Links

REFERENCE METHODS CHARACTERIZATION

RANGES

Markedly elevated erythrocyte sedimentation rates: consideration of clinical implications in a hospital population.

Lluberas-Acosta G, Schumacher HR Jr.

Jacquelyn McClure Lupus Center, Atlanta, Georgia, USA.
Br J Clin Pract 1996 Apr-May;50(3):138-42 Abstract quote
In order to evaluate the clinical significance of very high erythrocyte sedimentation rates (ESRs) we studied 100 consecutive men in a VA Medical Center whose Westergren ESR was more than 100mm/hr. All were followed for up to six months and the ESR-requesting physicians were interviewed. A total of 162 diagnoses known to be associated with an elevated ESR were present in the 90 patients available for follow up.

As in most previous series on very high ESRs, infections (seen in 43 patients) were the most common diagnoses. Other diagnoses included: malignancy (16), rheumatologic disease (30), other inflammatory diseases (seven), renal disease (25), and miscellaneous problems (38). Evaluation of 16 patients led to a diagnosis that had not initially been apparent--the ESR-requesting physician did not consider that a high ESR was instrumental in guiding him towards any of these delayed diagnoses.

Most of the markedly elevated ESRs in this patient population, requested in the context of already evident serious multisystem disease, contributed little diagnostic information.

Erythrocyte sedimentation rate in healthy school children of Bangladesh.

Zaman MM, Yoshiike N, Faruq QO, Ahmed J, Zareen S, Rouf MA, Haque KM, Tanaka H.

National Center for Control of Rheumatic Fever and Heart Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh.
J Epidemiol 2000 Mar;10(2):124-6 Abstract quote
The reference value of erythrocyte sedimentation rate (ESR) should be established for a population concerned because it is influenced by many local conditions. It has not yet been determined in healthy children of Bangladesh.

This study was done to determine the reference value of ESR in Bangladeshi children. ESR was determined in a sample of 413 'healthy' primary school students (259 boys and 154 girls, mean age 8.7 years). Ninety-five percent of them had ESR < or = 30 mm (Westergren 1 h).

Our findings suggest that ESR value > 30 mm (Westergren 1 h) should be considered high in Bangladeshi primary school children.

DMV ESR ANALYZER

Validation of the Diesse Mini-Ves Erythrocyte Sedimentation Rate (ESR) Analyzer Using the Westergren ESR Method in Patients With Systemic Inflammatory Conditions

Marc R. Happe, DO, etal.

Am J Clin Pathol 2002;118:14-17 Abstract quote

The Diesse Mini-Ves (DMV) erythrocyte sedimentation rate (ESR) analyzer was designed to improve efficiency in determining the ESR.

We compared the Westergren ESR method with the 4-sample DMV ESR analyzer for performance and clinical correlation. This prospective observational study, conducted at a 450-bed tertiary medical center, evaluated 291 paired samples from subjects with various systemic inflammatory conditions. Linear regression analysis revealed a statistically significant correlation between the 2 methods. Satisfactory precision of the DMV analyzer was obtained for high and mid-range ESR values. The 4-sample DMV ESR analyzer was precise and comparable in results to the Westergren ESR method.

This DMV ESR analyzer is now used at our medical center based on quality control improvements that include a faster, safer, and more standardized ESR method. Hospital or office-based clinical laboratories should consider using the 4-sample DMV ESR analyzer in place of the Westergren method.

WESTERGREN

Calibration and validation for erythrocyte sedimentation tests. Role of the International Committee on Standardization in Hematology reference procedure.

Thomas RD, Westengard JC, Hay KL, Bull BS.

Department of Pathology and Laboratory Medicine, Loma Linda (Calif), University School of Medicine, CA.
Arch Pathol Lab Med 1993 Jul;117(7):719-23 Abstract quote
The Westergren erythrocyte sedimentation rate (ESR) has been used for many years without any formal procedure for method validation or for quality assurance. In 1988, the International Committee on Standardization in Hematology (ICSH) (Leuven, Belgium) described an ESR validation procedure as well as a method for producing ESR reference material (ICSH reference method) in the laboratory where it is to be used. The ICSH proposal was tested in our laboratory during a consecutive period of 36 months.

In this article, a new mathematical relationship between the ICSH recommendation and the Westergren method is developed, which can be easily used for method validation and/or quality assurance. A table has been made that establishes 95% action limits for Westergren ESRs based on ICSH reference ESRs from 5 through 105 mm/h. The table, derived from 36 months of data, has been tested against two new data sets and used to validate two commercial ESR methods.

Analysis of outliers was performed with special attention to the mixing of whole blood samples with sodium citrate necessary for the Westergren ESR. This mixing process is best performed in a large-bore test tube as opposed to the use of the Westergren ESR tube as an aliquoting and mixing device.

CLINICAL UTILITY CHARACTERIZATION

GIANT CELL ARTERITIS

Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurence in a population-based study.

Salvarani C, Hunder GG.

Rheumatology Service, Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
Arthritis Rheum 2001 Apr;45(2):140-5 Abstract quote
OBJECTIVE: To determine the frequency of a low erythrocyte sedimentation rate (ESR) in patients with giant cell arteritis (GCA) and evaluate their clinical features in a defined population.

METHODS: A total of 167 patients with GCA were identified in the population of Olmsted County, Minnesota, between the years 1950 and 1998 using methods described in previous studies. All fulfilled American College of Rheumatology criteria for GCA.

RESULTS: In 9 of the 167 patients the ESR was less than 40 mm/hour (Westergren method) at diagnosis. These patients had less frequent systemic symptoms and visual symptoms than the others. No patient with low ESR developed blindness. Other manifestations were similar in those with low and those with high ESR. The response of symptoms to prednisone treatment was within 1 week, and after a median of 25 days of therapy the median ESR dropped from 19 mm/hour to 3 mm/hour. The median duration of glucocorticoid therapy in the 9 patients was 21.5 months and median followup after diagnosis was 12.5 years. Over a long period of observation (median 44 years) in the 9 patients with low ESR, 9 inflammatory events other than GCA were observed in 7 patients. The ESR was normal in 7 of these 9 other events.

CONCLUSION: A low ESR in active GCA is not a rare occurrence. Causes may include localized arteritis in some patients and an inability to mount an acute phase serologic response in others.

HEMODIALYSIS

The hematocrit-corrected erythrocyte sedimentation rate can be useful in diagnosing inflammation in hemodialysis patients.

Borawski J, Mysliwiec M.

Department of Nephrology and Internal Medicine, Medical Academy, Bialystok, Poland.
Nephron 2001 Dec;89(4):381-3 Abstract quote
BACKGROUND/AIMS: We aimed to determine predictors of erythrocyte sedimentation rate (ESR), and the ESR level pointing to the presence of inflammation in 60 chronic hemodialysis (HD) patients.

METHODS/RESULTS: On bivariate analysis, increased Westergren ESR of 62 (4-160) mm/h correlated inversely with hematocrit (Hct) and serum albumin, and positively with age, plasma fibrinogen, serum C-reactive protein (CRP), immunoglobulins A and G, alpha(1)-acid-glycoprotein and alpha(1)-antitrypsin. On multivariable analysis, independent predictors of the ESR were raised CRP (p < 0.0001), low Hct (p < 0.0001), increased fibrinogen (p < 0.0001) and immunoglobulin A (p = 0.009), and older age (p = 0.015). The Hct-corrected ESR level [ESR x (Hct/45)] of 38 (4-91) mm/h was independently predicted by CRP (p < 0.0001), fibrinogen (p < 0.0001), and age (p = 0.001). In the patients with normal CRP and albumin, the Hct-corrected ESR value was normal (23 mm/h) and lower than that of 59 mm/h in the subjects with elevated CRP and hypoalbuminemia. Using these cut-off points, the positive and negative predictive values of the Hct-corrected ESR on the presence of inflammation were 1.0, and its sensitivity and specificity were 100%.

CONCLUSION: Increased Westergren ESR in HD patients is associated with activated acute-phase response, anemia, and aging. The Hct-corrected ESR values of 23 and 59 mm/h precisely select the HD patients with severe inflammation from those without.

POLYMYALGIA RHEUMATICA

Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study.

Cantini F, Salvarani C, Olivieri I, Macchioni L, Ranzi A, Niccoli L, Padula A, Boiardi L.

Unita Reumatologica, 2nd Divisione di Medicina, Ospedale di Prato, Italy.
Semin Arthritis Rheum 2000 Aug;30(1):17-24 Abstract quote
OBJECTIVE: To determine the frequency and clinical features of patients with polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive protein (CRP) and ESR in the assessment of PMR activity.

METHODS: A prospective follow-up study on 177 consecutive patients meeting the criteria for PMR diagnosed over a 5-year period was conducted in two Italian secondary referral centers of rheumatology. At diagnosis and during follow-up, ESR (Westergren method) and CRP (nephelometry) were measured in all patients. Phenotypic analysis of lymphocyte subpopulations was performed on 78 PMR patients at diagnosis. A two-color technique using the association of specific monoclonal antibodies was applied. A control group consisting of 18 healthy adults older than 60 years was matched for age and sex with the PMR patients.

RESULTS: Ten of 177 (6%) patients had normal ESR values at diagnosis (< or = 30 mm/h). Patients with normal ESR were predominantly men and had lower CRP levels; systemic signs and symptoms were more frequent in patients with higher ESR. The percentages of circulating CD8+ cells were similar in the two groups. CRP values at diagnosis were normal in only 2 of 177 (1%) patients. CRP values were elevated in 9 of 10 patients with normal ESR at diagnosis. Twenty-five episodes of relapse/recurrence with normal ESR occurred in 17 patients. CRP was high in 62% of these episodes. Results of univariate analysis indicated that the 10th percentile for ESR (40 mm/h) and the 70th percentile for CRP (7.8 mg/dL) values at diagnosis were the best cutoff points that discriminate between patients with and without relapse/recurrence. Cox proportional hazards modeling showed that ESR greater than 40 mm/h and CRP greater than 7.8 mg/dL at diagnosis were the two variables that independently increased the risk of relapse/recurrence. However, the relative risk related to ESR was twice than that related to CRP (4.9 vs 2.1).

CONCLUSION: PMR with a normal ESR at diagnosis was infrequent in our study compared with previous studies. ESR was a superior predictor of relapse than CRP. However, CRP was a more sensitive indicator of current disease activity.

PREGNANCY

Pregnancy and the erythrocyte sedimentation rate.

van den Broe NR, Letsky EA.

Department of Reproductive Health, Liverpool School of Tropical Medicine, Liverpool, UK.
BJOG 2001 Nov;108(11):1164-7 Abstract quote
OBJECTIVES: To determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women. To examine the effect of gestational age and haemoglobin concentration on erythrocyte sedimentation rate.

SETTING: Queen Charlotte's Hospital, London, UK.

DESIGN: Cross sectional descriptive study. Population Healthy pregnant women attending for routine outpatient antenatal visits at Queen Charlotte's Hospital in London.

METHODS: Erythrocyte sedimentation rate was determined by the Westergren method, haemoglobin concentration by automated cell counter and gestational age by ultrasonography. The median and 95% reference range was determined for erythrocyte sedimentation rate values obtained. Linear regression analysis was used to determine the influence of haemoglobin concentration and gestational age on erythrocyte sedimentation rate.

RESULTS: For 1,019 women examined, the range of erythrocyte sedimentation rate values obtained was 4-112 mm/ h. Gestational age and haemoglobin concentration both significantly influenced erythrocyte sedimentation rate. (P < 0.0001). For non-anaemic women the 95% reference range rose from 18-48 mm/h in the first half of pregnancy to 30-70 mm/h in the second half of pregnancy. For anaemic women the corresponding reference ranges were 21-62 mm/h and 40-95 mm/h, respectively.

CONCLUSION: For the correct interpretation of erythrocyte sedimentation rate values obtained during pregnancy gestational age and haemoglobin concentration must be taken into account.

RHEUMATOID ARTHRITIS

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.

Paulus HE, Ramos B, Wong WK, Ahmed A, Bulpitt K, Park G, Sterz M, Clements P.

Department of Medicine, University of California Los Angeles, USA.
J Rheumatol 1999 Nov;26(11):2324-31 Abstract quote
OBJECTIVE: In an additive cohort of patients with early rheumatoid arthritis (RA), to determine the effect of substituting one acute phase reactant for another on the number of patients satisfying the American College of Rheumatology (ACR) 20% preliminary criteria for improvement, and on calculated Disease Activity Scores (DAS).

METHODS: A total of 251 patients with 6.4 months average disease duration had detailed clinical assessments at entry and 6, 12, and 24 months in a multicenter prospective longterm observational study. Matched erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma viscosity (PV) assays were done at 366 time points. Disease modifying antirheumatic drugs were not started until after the baseline evaluation.

RESULTS: After 6, 12, and 24 months, 50%, 53%, and 57% of patients were responders, as defined by the ACR 20% improvement criteria. The difference in response rates when ESR, CRP, or PV was used as the acute phase reactant ranged from 0.4% at 12 months to 3% at 24 months. Percentile distributions of the 366 matched CRP, ESR, and PV values were used to prepare a nomogram that can be used to calculate the other acute phase reactant values if the value of one is known. When the nomogram was used to impute ESR values from observed PV or CRP values, average DAS scores calculated with the actual ESR values were not different from average DAS scores calculated from the imputed ESR values.

CONCLUSION: ESR, CRP, and PV are equally useful in calculating ACR 20% response rates in patients with active early RA. A nomogram can be used to impute ESR values from CRP or PV values; use of the imputed ESR values is as accurate as use of the actual ESR values to calculate average DAS.

VASCULITIS

Comparison of factor VIII-related antigen and erythrocyte sedimentation rate in outpatient management of vasculitis.

Roberts WN, Brodeur JP, DeWitt J, Carr SZ, Wise CM, Carr ME.

Division of Rheumatology, Allergy & Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Angiology 1996 Nov;47(11):1081-7 Abstract quote
Electroimmunodiffusion (Laurell rocket) determinations of factor VIII-related antigen in plasma were ordered to determine the cost/benefit ratio for factor VIII-related antigen as a putative test for endothelial damage in suspected vasculitis. Twenty-seven consecutive patients referred for vasculitis or suspected vasculitis were identified and followed up for an average of 9.1 +/- months (range: one to thirty-three months) in a prospective, unblinded study performed in a clinic, associated with a 1054-bed inner-city university hospital.

There was no difference in Westergren erythrocyte sedimentation rate (WESR) in patients with final diagnosis of systemic vasculitis (SV) (38 +/- 12 mm/hour) compared to those without vasculitis (NV) (27 +/- 7) as the final diagnosis. The mean plasma concentration of factor VIII-related antigen was significantly elevated in SV (344 +/- 100%) when compared with NV (147 +/- 39%) (P < 0.016). The factor VIII-related antigen test in this study was 2.56 times more likely (crude odds ratio) than the WESR to contribute to a change in diagnosis or therapy (P = 0.016). Positive and negative predictive values (PPV and NPV) for factor VIII-related antigen (abnormal at greater than 220% of the normal value) were both 70%. PPV and NPV for WESR were 56% and 86%, respectively.

The factor VIII-related test was less cost-effective than the WESR in the follow-up period unless it was important to define complete remission or differentiate vasculitis flare from infection. The authors conclude that factor VIII-related antigen is a useful test in the initial diagnosis of vasculitis.

INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS CHARACTERIZATION

CONTROLS

Erythrocyte sedimentation rate: use of fresh blood for quality control.

Plebani M, Piva E.

Department of Laboratory Medicine, University-Hospital of Padua, Padova, Italy.obtained in fresh samples.
Am J Clin Pathol 2002 Apr;117(4):621-6 Abstract quote
The erythrocyte sedimentation rate (ESR) remains the most widely used laboratory test for monitoring the course of infections, inflammatory diseases, and some types of cancer. Several test methods have been developed recently, and as a result the safety and reliability of ESR testing procedures have improved. The method recommended by the International Council for Standardization in Haematology and the National Committee for Clinical Laboratory Standards for ESR measurement is based on the traditional Westergren method, using EDTA-anticoagulated samples without dilution. In clinical laboratories, reliable methods for calibration and the use of appropriate control materials are requiredfor monitoring the accuracy and precision of the routine method.

We describe and evaluate a procedure for achieving the daily quality control of ESR and for establishing the limits of agreement between working and reference methods. Data from routine patient samples were used to calculate the daily cumulative mean and to monitor its reproducibility over time. Finally, to monitor analytic performance, a comparison was made between results from the measurement of ESR in specimens stored at 4 degrees C for 24 hours and results obtained in fresh samples.

STRUCTURALLY ABNORMAL RED CELLS

Aggregation and sedimentation of mixtures of erythrocytes with different properties.

Suzuki Y, Tateishi N, Cicha I, Maeda N.

Department of Physiology, School of Medicine, Ehime University, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.
Clin Hemorheol Microcirc 2001;25(3-4):105-17 Abstract quote
The rouleau formation of erythrocytes and the erythrocyte sedimentation were examined for mixture of different kinds of the cells suspended in isotonic phosphate-buffered saline containing 1 or 2 g/dl dextran T-70 (MW = 70,400) and 4 g/dl albumin, using a low shear rheoscope and the Westergren method, respectively. The deformability of cells was decreased by treating with diamide, diazene-dicarboxylic acid bis[N,N-dimethylamide], and the sialic acid content of cells, i.e., the surface negative charge, was reduced by treating with neuraminidase.

(1) The rate of rouleau formation was decreased in cells with decreased deformability, while it was increased in cells with reduced sialic acid content. The rate changed in proportion to the ratio of the modified cells to normal cells. (2) The erythrocyte sedimentation was also decreased in cells with decreased deformability, while it was increased in cells with reduced sialic acid content. Furthermore, the erythrocyte sedimentation changed almost proportionally to the ratio of the modified cells to normal cells. (3) When normal deformable cells were mixed with cells with decreased deformability, the deformable cells seemed to settle faster than the less deformable cells, though the difference was not significant. (4) When normal cells were mixed with cells with reduced sialic acid content, the cells with less sialic acid settled significantly faster than those with more sialic acid.

The present experiment may conclude that erythrocyte aggregation is induced preferentially among more deformable cells and/or among less negatively charged cells with weaker electrostatic repulsive force, and then the formed aggregates settle faster.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.

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Last Modified 7/8/2002

REFERENCE METHODS	CHARACTERIZATION
RANGES
Markedly elevated erythrocyte sedimentation rates: consideration of clinical implications in a hospital population. Lluberas-Acosta G, Schumacher HR Jr. Jacquelyn McClure Lupus Center, Atlanta, Georgia, USA.	Br J Clin Pract 1996 Apr-May;50(3):138-42 Abstract quote In order to evaluate the clinical significance of very high erythrocyte sedimentation rates (ESRs) we studied 100 consecutive men in a VA Medical Center whose Westergren ESR was more than 100mm/hr. All were followed for up to six months and the ESR-requesting physicians were interviewed. A total of 162 diagnoses known to be associated with an elevated ESR were present in the 90 patients available for follow up. As in most previous series on very high ESRs, infections (seen in 43 patients) were the most common diagnoses. Other diagnoses included: malignancy (16), rheumatologic disease (30), other inflammatory diseases (seven), renal disease (25), and miscellaneous problems (38). Evaluation of 16 patients led to a diagnosis that had not initially been apparent--the ESR-requesting physician did not consider that a high ESR was instrumental in guiding him towards any of these delayed diagnoses. Most of the markedly elevated ESRs in this patient population, requested in the context of already evident serious multisystem disease, contributed little diagnostic information.
Erythrocyte sedimentation rate in healthy school children of Bangladesh. Zaman MM, Yoshiike N, Faruq QO, Ahmed J, Zareen S, Rouf MA, Haque KM, Tanaka H. National Center for Control of Rheumatic Fever and Heart Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh.	J Epidemiol 2000 Mar;10(2):124-6 Abstract quote The reference value of erythrocyte sedimentation rate (ESR) should be established for a population concerned because it is influenced by many local conditions. It has not yet been determined in healthy children of Bangladesh. This study was done to determine the reference value of ESR in Bangladeshi children. ESR was determined in a sample of 413 'healthy' primary school students (259 boys and 154 girls, mean age 8.7 years). Ninety-five percent of them had ESR < or = 30 mm (Westergren 1 h). Our findings suggest that ESR value > 30 mm (Westergren 1 h) should be considered high in Bangladeshi primary school children.
DMV ESR ANALYZER
Validation of the Diesse Mini-Ves Erythrocyte Sedimentation Rate (ESR) Analyzer Using the Westergren ESR Method in Patients With Systemic Inflammatory Conditions Marc R. Happe, DO, etal.	Am J Clin Pathol 2002;118:14-17 Abstract quote The Diesse Mini-Ves (DMV) erythrocyte sedimentation rate (ESR) analyzer was designed to improve efficiency in determining the ESR. We compared the Westergren ESR method with the 4-sample DMV ESR analyzer for performance and clinical correlation. This prospective observational study, conducted at a 450-bed tertiary medical center, evaluated 291 paired samples from subjects with various systemic inflammatory conditions. Linear regression analysis revealed a statistically significant correlation between the 2 methods. Satisfactory precision of the DMV analyzer was obtained for high and mid-range ESR values. The 4-sample DMV ESR analyzer was precise and comparable in results to the Westergren ESR method. This DMV ESR analyzer is now used at our medical center based on quality control improvements that include a faster, safer, and more standardized ESR method. Hospital or office-based clinical laboratories should consider using the 4-sample DMV ESR analyzer in place of the Westergren method.
WESTERGREN
Calibration and validation for erythrocyte sedimentation tests. Role of the International Committee on Standardization in Hematology reference procedure. Thomas RD, Westengard JC, Hay KL, Bull BS. Department of Pathology and Laboratory Medicine, Loma Linda (Calif), University School of Medicine, CA.	Arch Pathol Lab Med 1993 Jul;117(7):719-23 Abstract quote The Westergren erythrocyte sedimentation rate (ESR) has been used for many years without any formal procedure for method validation or for quality assurance. In 1988, the International Committee on Standardization in Hematology (ICSH) (Leuven, Belgium) described an ESR validation procedure as well as a method for producing ESR reference material (ICSH reference method) in the laboratory where it is to be used. The ICSH proposal was tested in our laboratory during a consecutive period of 36 months. In this article, a new mathematical relationship between the ICSH recommendation and the Westergren method is developed, which can be easily used for method validation and/or quality assurance. A table has been made that establishes 95% action limits for Westergren ESRs based on ICSH reference ESRs from 5 through 105 mm/h. The table, derived from 36 months of data, has been tested against two new data sets and used to validate two commercial ESR methods. Analysis of outliers was performed with special attention to the mixing of whole blood samples with sodium citrate necessary for the Westergren ESR. This mixing process is best performed in a large-bore test tube as opposed to the use of the Westergren ESR tube as an aliquoting and mixing device.

CLINICAL UTILITY	CHARACTERIZATION
GIANT CELL ARTERITIS
Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurence in a population-based study. Salvarani C, Hunder GG. Rheumatology Service, Arcispedale S. Maria Nuova, Reggio Emilia, Italy.	Arthritis Rheum 2001 Apr;45(2):140-5 Abstract quote OBJECTIVE: To determine the frequency of a low erythrocyte sedimentation rate (ESR) in patients with giant cell arteritis (GCA) and evaluate their clinical features in a defined population. METHODS: A total of 167 patients with GCA were identified in the population of Olmsted County, Minnesota, between the years 1950 and 1998 using methods described in previous studies. All fulfilled American College of Rheumatology criteria for GCA. RESULTS: In 9 of the 167 patients the ESR was less than 40 mm/hour (Westergren method) at diagnosis. These patients had less frequent systemic symptoms and visual symptoms than the others. No patient with low ESR developed blindness. Other manifestations were similar in those with low and those with high ESR. The response of symptoms to prednisone treatment was within 1 week, and after a median of 25 days of therapy the median ESR dropped from 19 mm/hour to 3 mm/hour. The median duration of glucocorticoid therapy in the 9 patients was 21.5 months and median followup after diagnosis was 12.5 years. Over a long period of observation (median 44 years) in the 9 patients with low ESR, 9 inflammatory events other than GCA were observed in 7 patients. The ESR was normal in 7 of these 9 other events. CONCLUSION: A low ESR in active GCA is not a rare occurrence. Causes may include localized arteritis in some patients and an inability to mount an acute phase serologic response in others.
HEMODIALYSIS
The hematocrit-corrected erythrocyte sedimentation rate can be useful in diagnosing inflammation in hemodialysis patients. Borawski J, Mysliwiec M. Department of Nephrology and Internal Medicine, Medical Academy, Bialystok, Poland.	Nephron 2001 Dec;89(4):381-3 Abstract quote BACKGROUND/AIMS: We aimed to determine predictors of erythrocyte sedimentation rate (ESR), and the ESR level pointing to the presence of inflammation in 60 chronic hemodialysis (HD) patients. METHODS/RESULTS: On bivariate analysis, increased Westergren ESR of 62 (4-160) mm/h correlated inversely with hematocrit (Hct) and serum albumin, and positively with age, plasma fibrinogen, serum C-reactive protein (CRP), immunoglobulins A and G, alpha(1)-acid-glycoprotein and alpha(1)-antitrypsin. On multivariable analysis, independent predictors of the ESR were raised CRP (p < 0.0001), low Hct (p < 0.0001), increased fibrinogen (p < 0.0001) and immunoglobulin A (p = 0.009), and older age (p = 0.015). The Hct-corrected ESR level [ESR x (Hct/45)] of 38 (4-91) mm/h was independently predicted by CRP (p < 0.0001), fibrinogen (p < 0.0001), and age (p = 0.001). In the patients with normal CRP and albumin, the Hct-corrected ESR value was normal (23 mm/h) and lower than that of 59 mm/h in the subjects with elevated CRP and hypoalbuminemia. Using these cut-off points, the positive and negative predictive values of the Hct-corrected ESR on the presence of inflammation were 1.0, and its sensitivity and specificity were 100%. CONCLUSION: Increased Westergren ESR in HD patients is associated with activated acute-phase response, anemia, and aging. The Hct-corrected ESR values of 23 and 59 mm/h precisely select the HD patients with severe inflammation from those without.
POLYMYALGIA RHEUMATICA
Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study. Cantini F, Salvarani C, Olivieri I, Macchioni L, Ranzi A, Niccoli L, Padula A, Boiardi L. Unita Reumatologica, 2nd Divisione di Medicina, Ospedale di Prato, Italy.	Semin Arthritis Rheum 2000 Aug;30(1):17-24 Abstract quote OBJECTIVE: To determine the frequency and clinical features of patients with polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive protein (CRP) and ESR in the assessment of PMR activity. METHODS: A prospective follow-up study on 177 consecutive patients meeting the criteria for PMR diagnosed over a 5-year period was conducted in two Italian secondary referral centers of rheumatology. At diagnosis and during follow-up, ESR (Westergren method) and CRP (nephelometry) were measured in all patients. Phenotypic analysis of lymphocyte subpopulations was performed on 78 PMR patients at diagnosis. A two-color technique using the association of specific monoclonal antibodies was applied. A control group consisting of 18 healthy adults older than 60 years was matched for age and sex with the PMR patients. RESULTS: Ten of 177 (6%) patients had normal ESR values at diagnosis (< or = 30 mm/h). Patients with normal ESR were predominantly men and had lower CRP levels; systemic signs and symptoms were more frequent in patients with higher ESR. The percentages of circulating CD8+ cells were similar in the two groups. CRP values at diagnosis were normal in only 2 of 177 (1%) patients. CRP values were elevated in 9 of 10 patients with normal ESR at diagnosis. Twenty-five episodes of relapse/recurrence with normal ESR occurred in 17 patients. CRP was high in 62% of these episodes. Results of univariate analysis indicated that the 10th percentile for ESR (40 mm/h) and the 70th percentile for CRP (7.8 mg/dL) values at diagnosis were the best cutoff points that discriminate between patients with and without relapse/recurrence. Cox proportional hazards modeling showed that ESR greater than 40 mm/h and CRP greater than 7.8 mg/dL at diagnosis were the two variables that independently increased the risk of relapse/recurrence. However, the relative risk related to ESR was twice than that related to CRP (4.9 vs 2.1). CONCLUSION: PMR with a normal ESR at diagnosis was infrequent in our study compared with previous studies. ESR was a superior predictor of relapse than CRP. However, CRP was a more sensitive indicator of current disease activity.
PREGNANCY
Pregnancy and the erythrocyte sedimentation rate. van den Broe NR, Letsky EA. Department of Reproductive Health, Liverpool School of Tropical Medicine, Liverpool, UK.	BJOG 2001 Nov;108(11):1164-7 Abstract quote OBJECTIVES: To determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women. To examine the effect of gestational age and haemoglobin concentration on erythrocyte sedimentation rate. SETTING: Queen Charlotte's Hospital, London, UK. DESIGN: Cross sectional descriptive study. Population Healthy pregnant women attending for routine outpatient antenatal visits at Queen Charlotte's Hospital in London. METHODS: Erythrocyte sedimentation rate was determined by the Westergren method, haemoglobin concentration by automated cell counter and gestational age by ultrasonography. The median and 95% reference range was determined for erythrocyte sedimentation rate values obtained. Linear regression analysis was used to determine the influence of haemoglobin concentration and gestational age on erythrocyte sedimentation rate. RESULTS: For 1,019 women examined, the range of erythrocyte sedimentation rate values obtained was 4-112 mm/ h. Gestational age and haemoglobin concentration both significantly influenced erythrocyte sedimentation rate. (P < 0.0001). For non-anaemic women the 95% reference range rose from 18-48 mm/h in the first half of pregnancy to 30-70 mm/h in the second half of pregnancy. For anaemic women the corresponding reference ranges were 21-62 mm/h and 40-95 mm/h, respectively. CONCLUSION: For the correct interpretation of erythrocyte sedimentation rate values obtained during pregnancy gestational age and haemoglobin concentration must be taken into account.
RHEUMATOID ARTHRITIS
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. Paulus HE, Ramos B, Wong WK, Ahmed A, Bulpitt K, Park G, Sterz M, Clements P. Department of Medicine, University of California Los Angeles, USA.	J Rheumatol 1999 Nov;26(11):2324-31 Abstract quote OBJECTIVE: In an additive cohort of patients with early rheumatoid arthritis (RA), to determine the effect of substituting one acute phase reactant for another on the number of patients satisfying the American College of Rheumatology (ACR) 20% preliminary criteria for improvement, and on calculated Disease Activity Scores (DAS). METHODS: A total of 251 patients with 6.4 months average disease duration had detailed clinical assessments at entry and 6, 12, and 24 months in a multicenter prospective longterm observational study. Matched erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma viscosity (PV) assays were done at 366 time points. Disease modifying antirheumatic drugs were not started until after the baseline evaluation. RESULTS: After 6, 12, and 24 months, 50%, 53%, and 57% of patients were responders, as defined by the ACR 20% improvement criteria. The difference in response rates when ESR, CRP, or PV was used as the acute phase reactant ranged from 0.4% at 12 months to 3% at 24 months. Percentile distributions of the 366 matched CRP, ESR, and PV values were used to prepare a nomogram that can be used to calculate the other acute phase reactant values if the value of one is known. When the nomogram was used to impute ESR values from observed PV or CRP values, average DAS scores calculated with the actual ESR values were not different from average DAS scores calculated from the imputed ESR values. CONCLUSION: ESR, CRP, and PV are equally useful in calculating ACR 20% response rates in patients with active early RA. A nomogram can be used to impute ESR values from CRP or PV values; use of the imputed ESR values is as accurate as use of the actual ESR values to calculate average DAS.
VASCULITIS
Comparison of factor VIII-related antigen and erythrocyte sedimentation rate in outpatient management of vasculitis. Roberts WN, Brodeur JP, DeWitt J, Carr SZ, Wise CM, Carr ME. Division of Rheumatology, Allergy & Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.	Angiology 1996 Nov;47(11):1081-7 Abstract quote Electroimmunodiffusion (Laurell rocket) determinations of factor VIII-related antigen in plasma were ordered to determine the cost/benefit ratio for factor VIII-related antigen as a putative test for endothelial damage in suspected vasculitis. Twenty-seven consecutive patients referred for vasculitis or suspected vasculitis were identified and followed up for an average of 9.1 +/- months (range: one to thirty-three months) in a prospective, unblinded study performed in a clinic, associated with a 1054-bed inner-city university hospital. There was no difference in Westergren erythrocyte sedimentation rate (WESR) in patients with final diagnosis of systemic vasculitis (SV) (38 +/- 12 mm/hour) compared to those without vasculitis (NV) (27 +/- 7) as the final diagnosis. The mean plasma concentration of factor VIII-related antigen was significantly elevated in SV (344 +/- 100%) when compared with NV (147 +/- 39%) (P < 0.016). The factor VIII-related antigen test in this study was 2.56 times more likely (crude odds ratio) than the WESR to contribute to a change in diagnosis or therapy (P = 0.016). Positive and negative predictive values (PPV and NPV) for factor VIII-related antigen (abnormal at greater than 220% of the normal value) were both 70%. PPV and NPV for WESR were 56% and 86%, respectively. The factor VIII-related test was less cost-effective than the WESR in the follow-up period unless it was important to define complete remission or differentiate vasculitis flare from infection. The authors conclude that factor VIII-related antigen is a useful test in the initial diagnosis of vasculitis.

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INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS	CHARACTERIZATION
CONTROLS
Erythrocyte sedimentation rate: use of fresh blood for quality control. Plebani M, Piva E. Department of Laboratory Medicine, University-Hospital of Padua, Padova, Italy.obtained in fresh samples.	Am J Clin Pathol 2002 Apr;117(4):621-6 Abstract quote The erythrocyte sedimentation rate (ESR) remains the most widely used laboratory test for monitoring the course of infections, inflammatory diseases, and some types of cancer. Several test methods have been developed recently, and as a result the safety and reliability of ESR testing procedures have improved. The method recommended by the International Council for Standardization in Haematology and the National Committee for Clinical Laboratory Standards for ESR measurement is based on the traditional Westergren method, using EDTA-anticoagulated samples without dilution. In clinical laboratories, reliable methods for calibration and the use of appropriate control materials are requiredfor monitoring the accuracy and precision of the routine method. We describe and evaluate a procedure for achieving the daily quality control of ESR and for establishing the limits of agreement between working and reference methods. Data from routine patient samples were used to calculate the daily cumulative mean and to monitor its reproducibility over time. Finally, to monitor analytic performance, a comparison was made between results from the measurement of ESR in specimens stored at 4 degrees C for 24 hours and results obtained in fresh samples.
STRUCTURALLY ABNORMAL RED CELLS
Aggregation and sedimentation of mixtures of erythrocytes with different properties. Suzuki Y, Tateishi N, Cicha I, Maeda N. Department of Physiology, School of Medicine, Ehime University, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.	Clin Hemorheol Microcirc 2001;25(3-4):105-17 Abstract quote The rouleau formation of erythrocytes and the erythrocyte sedimentation were examined for mixture of different kinds of the cells suspended in isotonic phosphate-buffered saline containing 1 or 2 g/dl dextran T-70 (MW = 70,400) and 4 g/dl albumin, using a low shear rheoscope and the Westergren method, respectively. The deformability of cells was decreased by treating with diamide, diazene-dicarboxylic acid bis[N,N-dimethylamide], and the sialic acid content of cells, i.e., the surface negative charge, was reduced by treating with neuraminidase. (1) The rate of rouleau formation was decreased in cells with decreased deformability, while it was increased in cells with reduced sialic acid content. The rate changed in proportion to the ratio of the modified cells to normal cells. (2) The erythrocyte sedimentation was also decreased in cells with decreased deformability, while it was increased in cells with reduced sialic acid content. Furthermore, the erythrocyte sedimentation changed almost proportionally to the ratio of the modified cells to normal cells. (3) When normal deformable cells were mixed with cells with decreased deformability, the deformable cells seemed to settle faster than the less deformable cells, though the difference was not significant. (4) When normal cells were mixed with cells with reduced sialic acid content, the cells with less sialic acid settled significantly faster than those with more sialic acid. The present experiment may conclude that erythrocyte aggregation is induced preferentially among more deformable cells and/or among less negatively charged cells with weaker electrostatic repulsive force, and then the formed aggregates settle faster.