Erythrocyte sedimentation rate

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.

There are three stages in erythrocyte sedimentation:{{cite web|title=Erythrocyte sedimentation rate (ESR)|url=http://www.nios.ac.in/media/documents/dmlt/hbbt/Lesson-08.pdf|publisher=National Institute of Open Schooling, India|access-date=8 April 2018|quote=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.}}

1. Rouleaux formation
2. Sedimentation or settling stage
3. 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.{{cite journal | last = Harrison | first = Michael | title = Erythrocyte sedimentation rate and C-reactive protein | journal = Australian Prescriber | volume = 38 | issue = 3 | pages = 93–4 | date = June 2015 | pmid = 26648629 | pmc = 4653962 | doi = 10.18773/austprescr.2015.034 }}

The rate of erythrocyte sedimentation is affected by both inflammatory and non-inflammatory conditions.

In inflammatory conditions, fibrinogen, other clotting proteins, and alpha globulin are positively charged, thus increasing the ESR. 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.

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. ESR is also higher in women during menstruation and pregnancy. 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.{{cite journal | vauthors = Arik N, Bedir A, Günaydin M, Adam B, Halefi I | s2cid = 5967575 | title = Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? | journal = Nephron | volume = 86 | issue = 2 | pages = 224 | date = October 2000 | pmid = 11015011 | doi = 10.1159/000045760 | type = Letter to the editor | url = https://www.researchgate.net/publication/12308738 }}

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|date=July 2020}}

ESR can sometimes be useful in diagnosing diseases, such as multiple myeloma, temporal arteritis, polymyalgia rheumatica, various autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease{{cite journal | vauthors = Liu S, Ren J, Xia Q, Wu X, Han G, Ren H, Yan D, Wang G, Gu G, Li J | s2cid = 5173681 | title = 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 | journal = The American Journal of the Medical Sciences | volume = 346 | issue = 6 | pages = 467–72 | date = December 2013 | pmid = 23689052 | doi = 10.1097/MAJ.0b013e3182959a18 }} and chronic kidney diseases. In many of these cases, the ESR may exceed 100 mm/hour.{{cite web |title=Sedimentation Rate |url=http://www.webmd.com/a-to-z-guides/sedimentation-rate |date=2006-06-16 |publisher=WebMD |access-date=2008-03-01}}

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%).{{cite journal|last1=Raiten|first1=Daniel J|last2=Ashour|first2=Fayrouz A Sakr|last3=Ross|first3=A Catharine|last4=Meydani|first4=Simin N|last5=Dawson|first5=Harry D|last6=Stephensen|first6=Charles B|last7=Brabin|first7=Bernard J|last8=Suchdev|first8=Parminder S|last9=van Ommen|first9=Ben|title=Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE)|journal=The Journal of Nutrition|volume=145|issue=5|year=2015|pages=1039S–1108S|issn=0022-3166|doi=10.3945/jn.114.194571|pmid=25833893|pmc=4448820}}
-Which cites: {{cite journal|last1=Fincher|first1=Ruth-Marie E.|title=Clinical Significance of Extreme Elevation of the Erythrocyte Sedimentation Rate|journal=Archives of Internal Medicine|volume=146|issue=8|year=1986|pages=1581–3|issn=0003-9926|doi=10.1001/archinte.1986.00360200151024|pmid=3729639}} Yet, in pneumonia the ESR stays under 100.{{cite journal|last1=Falk|first1=G.|last2=Fahey|first2=T.|title=C-reactive protein and community-acquired pneumonia in ambulatory care: systematic review of diagnostic accuracy studies|journal=Family Practice|volume=26|issue=1|year=2008|pages=10–21|issn=0263-2136|doi=10.1093/fampra/cmn095|pmid=19074757|doi-access=free}}

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.{{Cite journal | s2cid=7244484| doi=10.1086/322605| title=Why Shouldn't We Determine the Erythrocyte Sedimentation Rate?| year=2001| last1=Jurado| first1=Rafael L.| journal=Clinical Infectious Diseases| volume=33| issue=4| pages=548–549| pmid=11462193| doi-access=free}} Current literature suggests that an ESR should be "obtained on all patients over the age of 50" who have an intense headache.{{Citation |last1=Diamond |first1=Seymour |title=Chapter 27 - Acute Headache |date=2011-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9781437707212000271 |work=Pain Management (Second Edition) |pages=249–257 |editor-last=Waldman |editor-first=Steven D. |place=Philadelphia |publisher=W.B. Saunders |language=en |doi=10.1016/b978-1-4377-0721-2.00027-1 |isbn=978-1-4377-0721-2 |access-date=2022-05-24 |last2=Nissan |first2=George R.|url-access=subscription }}

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|date=November 2021}}

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|date=July 2020}}

Note: mm/h. = millimeters per hour.

Westergren's original normal values (men 3 mm/h and women 7 mm/h){{cite journal | vauthors = Westergren A | title = Diagnostic tests: the erythrocyte sedimentation rate range and limitations of the technique | journal = Triangle; the Sandoz Journal of Medical Science | volume = 3 | issue = 1 | pages = 20–5 | date = March 1957 | pmid = 13455726 }} 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.{{cite journal | vauthors = Böttiger LE, Svedberg CA | title = Normal erythrocyte sedimentation rate and age | journal = British Medical Journal | volume = 2 | issue = 5544 | pages = 85–7 | date = April 1967 | pmid = 6020854 | pmc = 1841240 | doi = 10.1136/bmj.2.5544.85 }}

Values of the ESR also appear to be slightly higher in normal populations of African-Americans than Caucasians of both genders.{{cite journal | vauthors = Gillum RF | title = A racial difference in erythrocyte sedimentation | journal = Journal of the National Medical Association | volume = 85 | issue = 1 | pages = 47–50 | date = January 1993 | pmid = 8426384 | pmc = 2571720 }} Values also appear to be higher in anemic individuals than non-anemic individuals.{{cite journal | vauthors = Kanfer EJ, Nicol BA | title = Haemoglobin concentration and erythrocyte sedimentation rate in primary care patients | journal = Journal of the Royal Society of Medicine | volume = 90 | issue = 1 | pages = 16–8 | date = January 1997 | pmid = 9059375 | pmc = 1296109 | doi = 10.1177/014107689709000106| format = Scanned & PDF }}

The widely used{{Cite GPnotebook|389349443|Reference range (ESR)}} 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:{{cite journal | vauthors = Miller A, Green M, Robinson D | title = Simple rule for calculating normal erythrocyte sedimentation rate | journal = British Medical Journal | volume = 286 | issue = 6361 | pages = 266 | date = January 1983 | pmid = 6402065 | pmc = 1546487 | doi = 10.1136/bmj.286.6361.266 }} 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.

:$\{\backslash rm\; ESR\}\backslash \; (mm/h)\; \backslash le\; \backslash frac\; \{\{\backslash rm\; Age\}\backslash \; (\{\backslash it\; in\backslash \; years\})\; +\; 10\backslash \; (\{\backslash it\; if\backslash \; female\})\}\{2\}$

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):{{cite journal | vauthors = Wetteland P, Røger M, Solberg HE, Iversen OH | title = Population-based erythrocyte sedimentation rates in 3910 subjectively healthy Norwegian adults. A statistical study based on men and women from the Oslo area | journal = Journal of Internal Medicine | volume = 240 | issue = 3 | pages = 125–31 | date = September 1996 | pmid = 8862121 | doi = 10.1046/j.1365-2796.1996.30295851000.x | s2cid = 10871066 }} - listing upper reference levels expected to be exceeded only by chance in 5% of subjects

Normal values of ESR have been quoted as 1{{cite journal | vauthors = Adler SM, Denton RL | title = The erythrocyte sedimentation rate in the newborn period | journal = The Journal of Pediatrics | volume = 86 | issue = 6 | pages = 942–8 | date = June 1975 | pmid = 1168702 | doi = 10.1016/S0022-3476(75)80233-2 }} to 2{{cite journal | vauthors = Ibsen KK, Nielsen M, Prag J, Hørlyk H, Vrang C, Korner B, Peitersen B | title = The value of the micromethod erythrocyte sedimentation rate in the diagnosis of infections in newborns | journal = Scandinavian Journal of Infectious Diseases. Supplementum | volume = Suppl 23 | pages = 143–5 | year = 1980 | pmid = 6937959 }} mm/h at birth, rising to 4 mm/h 8 days after delivery, and then to 17 mm/h by day 14.

Typical normal ranges quoted are:

• Newborn: 0 to 2 mm/h
• Neonatal to puberty: 3 to 13 mm/h, but other laboratories place an upper limit of 20.{{cite journal | vauthors = ((Pediatric Inflammatory Bowel Disease Collaborative Research Group )), Mack DR, Langton C, Markowitz J, LeLeiko N, Griffiths A, Bousvaros A, Evans J, Kugathasan S, Otley A, Pfefferkorn M, Rosh J, Mezoff A, Moyer S, Oliva-Hemker M, Rothbaum R, Wyllie R, delRosario JF, Keljo D, Lerer T, Hyams J |display-authors = 6| title = Laboratory values for children with newly diagnosed inflammatory bowel disease | journal = Pediatrics | volume = 119 | issue = 6 | pages = 1113–9 | date = June 2007 | pmid = 17545378 | doi = 10.1542/peds.2006-1865 | s2cid = 5558076}}
• {{lay source |template=cite web|vauthors = Bauchner H|url= https://www.jwatch.org/pa200706130000002/2007/06/13/lab-screening-children-with-suspected|title= Lab Screening in Children with Suspected Inflammatory Bowel Disease|date= July 13, 2007 |website= NEJM Journal Watch }}

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{{cite journal | vauthors = Bray C, Bell LN, Liang H, Haykal R, Kaiksow F, Mazza JJ, Yale SH | title = Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine | journal = WMJ | volume = 115 | issue = 6 | pages = 317–21 | date = December 2016 | pmid = 29094869 | url = http://www.wisconsinmedicalsociety.org/_WMS/publications/wmj/pdf/115/6/317.pdf }} in 12.5% of the cases. 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.{{Cite journal|last1=Enocsson|first1=Helena|last2=Sjöwall|first2=Christopher|last3=Skogh|first3=Thomas|last4=Eloranta|first4=Maija-Leena|last5=Rönnblom|first5=Lars|last6=Wetterö|first6=Jonas|date=December 2009|title=Interferon-α mediates suppression of C-reactive protein: Explanation for muted C-reactive protein response in lupus flares?|url=https://onlinelibrary.wiley.com/doi/10.1002/art.25042|journal=Arthritis & Rheumatism|language=en|volume=60|issue=12|pages=3755–3760|doi=10.1002/art.25042|pmid=19950271 }} CRP is a better marker for other autoimmune diseases such as polymyalgia rheumatica, giant cell arteritis, post-operative sepsis, and neonatal sepsis. ESR may be reduced in those who are taking statins and non-steroidal anti-inflammatory drugs (NSAIDs).

The test was invented in 1897 by the Polish pathologist Edmund Biernacki.{{cite book |title=Dzieje nauki polskiej|last= Iłowiecki|first=Maciej|year=1981|publisher=Wydawnictwo "Interpress"|location= Warszawa|page= 195|isbn=978-83-223-1876-8}}{{WhoNamedIt2|doctor|2783|Edmund Faustyn Biernacki}} and eponymously named {{WhoNamedIt|synd|3352|Biernacki's test}} In some parts of the world the test continues to be referred to as Biernacki's Reaction ({{langx|pl|odczyn Biernackiego}}, OB). 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. 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),{{WhoNamedIt2|doctor|2788|Robert (Robin) Sanno Fåhræus}} and {{WhoNamedIt2|doctor|2791|Alf Vilhelm Albertsson Westergren}} who are eponymously named for the {{WhoNamedIt|synd|3359|Fåhræus-Westergren test (aka Westergren test)}} which uses sodium citrate-anti-coagulated specimens.{{cite journal | author = International Council for Standardization in Haematology (Expert Panel on Blood Rheology) | title = ICSH recommendations for measurement of erythrocyte sedimentation rate. International Council for Standardization in Haematology (Expert Panel on Blood Rheology) | journal = Journal of Clinical Pathology | volume = 46 | issue = 3 | pages = 198–203 | date = March 1993 | pmid = 8463411 | pmc = 501169 | doi = 10.1136/jcp.46.3.198 }}

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.{{cite journal | vauthors = Sidore C, Busonero F, Maschio A, Porcu E, Naitza S, Zoledziewska M, Mulas A, Pistis G, Steri M, Danjou F, Kwong A, Ortega Del Vecchyo VD, Chiang CW, Bragg-Gresham J, Pitzalis M, Nagaraja R, Tarrier B, Brennan C, Uzzau S, Fuchsberger C, Atzeni R, Reinier F, Berutti R, Huang J, Timpson NJ, Toniolo D, Gasparini P, Malerba G, Dedoussis G, Zeggini E, Soranzo N, Jones C, Lyons R, Angius A, Kang HM, Novembre J, Sanna S, Schlessinger D, Cucca F, Abecasis GR | display-authors = 6 | title = Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers | journal = Nature Genetics | volume = 47 | issue = 11 | pages = 1272–1281 | date = November 2015 | pmid = 26366554 | pmc = 4627508 | doi = 10.1038/ng.3368 }}

According to a 2010 study, there is a reverse correlation between ESR and general intelligence (IQ) in Swedish males aged 18–20.{{cite journal |last1=Karlsson |first1=Håkan |last2=Ahlborg |first2=Björn |last3=Dalman |first3=Christina |last4=Hemmingsson |first4=Tomas |s2cid=7185302 |title=Association between erythrocyte sedimentation rate and IQ in Swedish males aged 18–20 |journal=Brain, Behavior, and Immunity |date=August 2010 |volume=24 |issue=6 |pages=868–873 |doi=10.1016/j.bbi.2010.02.009|pmid=20226851 }}

{{Reflist|30em}}

• [https://www.mediscuss.org/erythrocyte-sedimentation-rate/ Mediscuss on ESR]
• {{cite journal | vauthors = Brigden ML | title = Clinical utility of the erythrocyte sedimentation rate | journal = American Family Physician | volume = 60 | issue = 5 | pages = 1443–50 | date = October 1999 | pmid = 10524488 | url = http://www.aafp.org/link_out?pmid=10524488 }}
• [https://www.testing.com/tests/erythrocyte-sedimentation-rate-esr/ ESR] at Lab Tests Online

{{Inflammation}}

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Category:Blood tests

Category:Temporal rates