Erythrocyte sedimentation rate
The erythrocyte sedimentation 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 mm at the end of one hour.
Since the introduction of automated analyzers into the clinical laboratory, the ESR test has been automatically performed.
The ESR is governed by the balance between pro-sedimentation factors, mainly fibrinogen, and those factors resisting sedimentation, namely the negative charge of the erythrocytes. When an inflammatory process is present, the high proportion of fibrinogen in the blood causes red blood cells to stick to each other. The red cells form stacks called rouleaux which settle faster, due to their increased density. Rouleaux formation can also occur in association with some lymphoproliferative disorders in which one or more paraproteins are secreted in high amounts. While abnormal in humans, rouleaux formation can be a normal physiological finding in horses, cats, and pigs.
The ESR is increased in inflammation, pregnancy, anemia, autoimmune disorders, infections, some kidney diseases and some cancers. The ESR is decreased in polycythemia, hyperviscosity, sickle cell anemia, leukemia, chronic fatigue syndrome, low plasma protein and congestive heart failure. Although increases in immunoglobulins usually increase the ESR, very high levels can reduce it again due to hyperviscosity of the plasma. This is especially likely with IgM-class paraproteins, and to a lesser extent, IgA-class. The basal ESR is slightly higher in females.
Stages
Erythrocyte sedimentation rate is the measure of ability of erythrocytes to fall through the blood plasma and accumulate together at the base of container in one hour.There are 3 stages in erythrocyte sedimentation:
- Rouleaux formation
- Sedimentation or settling stage
- Packing stage - 10 minutes
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. 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, investigations should be done to find the underlying causes because there is a 90% probability that cause would be found.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. 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.Causes of reduction
An increased number of red blood cells 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.Medical uses
Diagnosis
ESR can sometimes be useful in diagnosing diseases, such as multiple myeloma, temporal arteritis, polymyalgia rheumatica, various auto-immune diseases, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease and chronic kidney diseases. In many of these cases, the ESR may exceed 100 mm/hour.It is commonly used for a differential diagnosis for Kawasaki's disease 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, followed by cancer, kidney disease and noninfectious inflammatory disorders. Yet, in pneumonia the ESR stays under 100.
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.
Disease severity
It is a component of the PCDAI, an index for assessment of the severity of inflammatory bowel disease in children.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.Normal values
Note: mm/h. = millimeters per hour.Westergren's original normal values 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.
Values of the ESR also appear to be slightly higher in normal populations of African-Americans than Caucasians of both genders. Values also appear to be higher in anemic individuals than non-anemic individuals.
Adults
The widely used rule calculating normal maximum ESR values in adults is given by a formula devised in 1983 from a study of ≈1000 individuals over the age of 20: The normal values of ESR in men is age divided by 2; for women, the normal value is age plus 10, divided by 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 :
Children
Normal values of ESR have been quoted as 1 to 2 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.
Relation to C-reactive protein
| High ESR/Low CRP | Low ESR/High CRP |
| Systemic lupus erythematosis Bone and joint infections Ischemic stroke Waldenstrom's macroglobulinemia Multiple myeloma IgG4 related disease Chronic kidney disease Low serum albumin | 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. In some parts of the world the test continues to be referred to as Biernacki's Reaction. In 1918, Dr Robert Fahraeus 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 Fahraeus and Alf Vilhelm Albertsson Westergren are eponymously remembered for the Fåhræus-Westergren test, which uses sodium citrate-anti-coagulated specimens.Research
According to a study released in 2015, a stop gain mutation in HBB gene 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.According to a 2010 study, there is a reverse correlation between ESR and general intelligence in swedish males aged 18-20