Westergren pipet array on StaRRsed automated ESR analyzer. The ESR is the height (in mm) of the colourless portion at the top of the pipette after one hour.
The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation.
To perform the test, anticoagulated blood is traditionally placed in an upright tube, known as a Westergren tube, and the distance which the red blood cells fall is measured and reported in millimetres at the end of one hour.[3]
Since the introduction of automated analyzers into the clinical laboratory, the ESR test has been automatically performed.
The ESR is influenced by the aggregation of red blood cells: blood plasma proteins, mainly fibrinogen, promote the formation of red cell clusters called rouleaux or larger structures (interconnected rouleaux, irregular clusters). As according to Stokes' law the sedimentation velocity varies like the square of the object's diameter, larger aggregates settle faster. While aggregation already takes place at normal physiological fibrinogen levels, these tend to increase when an inflammatory process is present, leading to increased ESR.
Erythrocyte sedimentation rate (ESR) is the measure of ability of erythrocytes (red blood cell) to fall through the blood plasma and accumulate together at the base of container in one hour.[7]
There are three stages in erythrocyte sedimentation:[8]
Rouleaux formation
Sedimentation or settling stage
Packing stage - 10 minutes (sedimentation slows and cells start to pack at the bottom of the tube)
In normal conditions, the red blood cells are negatively charged and therefore repel each other rather than stacking. ESR is also reduced by high blood viscosity, which slows the rate of fall.[7]
Causes of elevation
The rate of erythrocyte sedimentation is affected by both inflammatory and non-inflammatory conditions.
Inflammation
In inflammatory conditions, fibrinogen, other clotting proteins, and alpha globulin are positively charged, thus increasing the ESR.[9] ESR begins to rise at 24 to 48 hours after the onset of acute self-limited inflammation, decreases slowly as inflammation resolves, and can take weeks to months to return to normal levels. For ESR values more than 100 mm/hour, there is a 90% probability that an underlying cause would be found upon investigation.[9]
Non-inflammatory conditions
In non-inflammatory conditions, plasma albumin concentration, size, shape, and number of red blood cells, and the concentration of immunoglobulin can affect the ESR. Non-inflammatory conditions that can cause raised ESR include anemia, kidney failure, obesity, ageing, and female sex.[7] ESR is also higher in women during menstruation and pregnancy.[9] The value of ESR does not change whether dialysis is performed or not. Therefore, ESR is not a reliable measure of inflammation in those with kidney injuries as the ESR value is already elevated.[10]
Causes of reduction
An increased number of red blood cells (polycythemia) causes reduced ESR as blood viscosity increases. Hemoglobinopathy such as sickle-cell disease can have low ESR due to an improper shape of red blood cells that impairs stacking.[citation needed]
It is commonly used for a differential diagnosis for Kawasaki's disease (from Takayasu's arteritis; which would have a markedly elevated ESR) and it may be increased in some chronic infective conditions like tuberculosis and infective endocarditis. It is also elevated in subacute thyroiditis also known as DeQuervain's.
In markedly increased ESR of over 100 mm/h, infection is the most common cause (33% of cases in an American study), followed by cancer (17%), kidney disease (17%) and noninfectious inflammatory disorders (14%).[13] Yet, in pneumonia the ESR stays under 100.[14]
The usefulness of the ESR in current practice has been questioned by some, as it is a relatively imprecise and non-specific test compared to other available diagnostic tests.[15] Current literature suggests that and ESR should be "obtained on all patients over the age of 50" who have an intense headache.[16]
Disease severity
It is a component of the PCDAI (pediatric Crohn's disease activity index), an index for assessment of the severity of inflammatory bowel disease in children.[citation needed]
Monitoring response to therapy
The clinical usefulness of ESR is limited to monitoring the response to therapy in certain inflammatory diseases such as temporal arteritis, polymyalgia rheumatica and rheumatoid arthritis. It can also be used as a crude measure of response in Hodgkin's lymphoma. Additionally, ESR levels are used to define one of the several possible adverse prognostic factors in the staging of Hodgkin's lymphoma.[citation needed]
Normal values
Note: mm/h. = millimeters per hour.
Westergren's original normal values (men 3 mm/h and women 7 mm/h)[17] made no allowance for a person's age. Later studies from 1967 confirmed that ESR values tend to rise with age and to be generally higher in women.[18]
Values of the ESR also appear to be slightly higher in normal populations of African-Americans than Caucasians of both genders.[19] Values also appear to be higher in anemic individuals than non-anemic individuals.[20]
Adults
The widely used[21] rule calculating normal maximum ESR values in adults (98% confidence limit) is given by a formula devised in 1983 from a study of ≈1000 individuals over the age of 20:[22] The normal values of ESR in men is age (in years) divided by 2; for women, the normal value is age (in years) plus 10, divided by 2.[9]
Other studies confirm a dependence of ESR on age and gender, as seen in the following:
ESR reference ranges from a large 1996 study of 3,910 healthy adults (NB. these use 95% confidence intervals rather than the 98% intervals used in the study used to derive the formula above, and because of the skewness of the data, these values appear to be less than expected from the above formula):[23]
Age
20
55
90
Men—5% exceed
12
14
19
Women—5% exceed
18
21
23
Children
Normal values of ESR have been quoted as 1[24] to 2[25] mm/h at birth, rising to 4 mm/h 8 days after delivery,[25] and then to 17 mm/h by day 14.[24]
Neonatal to puberty: 3 to 13 mm/h, but other laboratories place an upper limit of 20.[26]
Relation to C-reactive protein
C-reactive protein (CRP) is an acute phase protein. Therefore, it is a better marker for acute phase reaction than ESR. While ESR and CRP generally together correlate with the degree of inflammation, this is not always the case and results may be discordant[9] in 12.5% of the cases.[7] Cases with raised CRP but normal ESR may demonstrate a combination of infection and some other tissue damage such as myocardial infarction, and venous thromboembolism. Such inflammation may not be enough to raise the level of ESR. Those with high ESR usually do not have demonstrable inflammation. However, in cases of low grade bacterial infections of bone and joints such as coagulase negative staphylococcus (CoNS), and systemic lupus erythematosus (SLE), ESR can be a good marker for the inflammatory process. This may be due to the production of Interferon type I that inhibits the CRP production in liver cells during SLE.[27] CRP is a better marker for other autoimmune diseases such as polymyalgia rheumatica, giant cell arteritis,[7] post-operative sepsis, and neonatal sepsis. ESR may be reduced in those who are taking statins and non-steroidal anti-inflammatory drugs (NSAIDs).[9]
Urinary tract, GI, lung and bloodstream infections
Myocardial infarction
Venous thromboembolic disease
Rheumatoid arthritis
Low serum albumin
History
The test was invented in 1897 by the Polish pathologist Edmund Biernacki.[28][29] In some parts of the world the test continues to be referred to as Biernacki's Reaction (Polish: odczyn Biernackiego, OB).[30] In 1918, Dr Robert Fåhræus noted that ESR differed only during pregnancy. Therefore, he suggested that ESR could be used as an indicator of pregnancy. In 1921, Dr Alf Vilhelm Albertsson Westergren used ESR to measure the disease outcome of tuberculosis. He defined the measurement standards of ESR which is still being used today.[7] Robert Fåhræus and Alf Vilhelm Albertsson Westergren are eponymously remembered for the 'Fahraeus-Westergren test' (abbreviated as FW test; in the UK, usually termed Westergren test),[30] which uses sodium citrate-anti-coagulated specimens.[31]
Research
According to a study released in 2015, a stop gain mutation in HBB gene (p. Gln40stop) was shown to be associated with ESR values in Sardinian population. The red blood cell count, whose values are inversely related to ESR, is affected in carriers of this SNP. This mutation is almost exclusive of the inhabitants of Sardinia and is a common cause of beta thalassemia.[32]
According to a 2010 study, there is a reverse correlation between ESR and general intelligence (IQ) in Swedish males aged 18–20.[33]
^"Erythrocyte sedimentation rate (ESR)"(PDF). National Institute of Open Schooling, India. Retrieved 8 April 2018. Sedimentation occurs in three stages. In the first stage, the red cells form rouleaux. In the second stage, sinking of the aggregates occurs at a constant speed. In the final stage, the rate of sedimentation slows as the aggregated cells pack at the bottom of the tube.
^Liu S, Ren J, Xia Q, Wu X, Han G, Ren H, Yan D, Wang G, Gu G, Li J (December 2013). "Preliminary case-control study to evaluate diagnostic values of C-reactive protein and erythrocyte sedimentation rate in differentiating active Crohn's disease from intestinal lymphoma, intestinal tuberculosis and Behcet's syndrome". The American Journal of the Medical Sciences. 346 (6): 467–72. doi:10.1097/MAJ.0b013e3182959a18. PMID23689052. S2CID5173681.
^Westergren A (March 1957). "Diagnostic tests: the erythrocyte sedimentation rate range and limitations of the technique". Triangle; the Sandoz Journal of Medical Science. 3 (1): 20–5. PMID13455726.
^Wetteland P, Røger M, Solberg HE, Iversen OH (September 1996). "Population-based erythrocyte sedimentation rates in 3910 subjectively healthy Norwegian adults. A statistical study based on men and women from the Oslo area". Journal of Internal Medicine. 240 (3): 125–31. doi:10.1046/j.1365-2796.1996.30295851000.x. PMID8862121. S2CID10871066. - listing upper reference levels expected to be exceeded only by chance in 5% of subjects
^ abAdler SM, Denton RL (June 1975). "The erythrocyte sedimentation rate in the newborn period". The Journal of Pediatrics. 86 (6): 942–8. doi:10.1016/S0022-3476(75)80233-2. PMID1168702.
^ abIbsen KK, Nielsen M, Prag J, Hørlyk H, Vrang C, Korner B, Peitersen B (1980). "The value of the micromethod erythrocyte sedimentation rate in the diagnosis of infections in newborns". Scandinavian Journal of Infectious Diseases. Supplementum. Suppl 23: 143–5. PMID6937959.
^Pediatric Inflammatory Bowel Disease Collaborative Research Group , Mack DR, Langton C, Markowitz J, LeLeiko N, Griffiths A, et al. (June 2007). "Laboratory values for children with newly diagnosed inflammatory bowel disease". Pediatrics. 119 (6): 1113–9. doi:10.1542/peds.2006-1865. PMID17545378. S2CID5558076.
^Karlsson, Håkan; Ahlborg, Björn; Dalman, Christina; Hemmingsson, Tomas (August 2010). "Association between erythrocyte sedimentation rate and IQ in Swedish males aged 18–20". Brain, Behavior, and Immunity. 24 (6): 868–873. doi:10.1016/j.bbi.2010.02.009. PMID20226851. S2CID7185302.
