Erythrocyte sedimentation rate

The erythrocyte sedimentation rate (ESR), also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test that is a non-specific measure of inflammation. To perform the test, anticoagulated blood is placed in an upright tube, known as a Westergren tube, and the rate at which the red blood cells fall is measured and reported in mm/h.
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 (zeta potential). 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. Rouleaux formation can also occur in association with some lymphoproliferative disorders in which one or more immunoglobulin/s is/are secreted in high amounts. Rouleaux formation can, however, be a normal physiological finding in horses, cats, and pigs.

The ESR is increased by any cause or focus of inflammation. The ESR is increased in pregnancy or rheumatoid arthritis, and decreased in polycythemia, sickle cell anemia, hereditary spherocytosis, and congestive heart failure. The basal ESR is slightly higher in females.
History
This test was invented in 1897 by the Polish doctor Edmund Biernacki. In some parts of the world the test continues to be referred to as the Biernacki Test (Polish abbreviation: OB = Odczyn Biernackiego.) In 1918 the Swedish pathologist Robert Sanno Fåhræus declared the same and along with Alf Vilhelm Albertsson Westergren are eponymously remembered for the Fåhræus-Westergren test (abbreviated as FW test; in the UK, usually termed Westergren test), which uses sodium citrate-anticoagulated specimens.

Uses

Although it is frequently ordered, ESR is of limited use as a screening test in asymptomatic patients. It is useful for diagnosing diseases, such as multiple myeloma, temporal arteritis, polymyalgia rheumatica, various auto-immune diseases, systemic lupus erythematosus, rheumatoid arthritis, 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 a component of the PDCAI, an index for assessment of severity of inflammatory bowel disease in children.
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. There is also a wintrobe method.
The use of the ESR as a screening test in asymptomatic persons is limited by its low sensitivity and specificity. When there is a moderate suspicion of disease, the ESR may have some value as a "sickness index."
An elevated ESR in the absence of other findings should not trigger an extensive laboratory or radiographic evaluation.

Normal Values

Note: mm/hr. = millimeters per hour.

Westergren's original normal values (men 3mm and women 7mm) made no allowance for a person's age and in 1967 it was confirmed that ESR values tend to rise with age and to be generally higher in women. Values are increased in states of anemia, and in black populations.

Adults

The widely used rule for calculating normal maximum ESR values in adults (98% confidence limit) is given by a formula devised in 1983: ESR reference ranges from a large 1996 study with weaker confidence limits:

Age	20	55	90
Men	12	14	19
Women	18	21	23

Children

Normal values of ESR have been quoted as 1 to 2 mm/hr at birth, rising to 4 mm/hr 8 days after delivery,and then to 17 mm/hr by day 14.
Typical normal ranges quoted are:
 Newborn: 0 to 2 mm/hr

• Neonatal to puberty: 3 to 13 mm/hr, but other laboratories place an upper limit of 20.

Relation to C-reactive protein

C-reactive protein is an acute phase protein produced by the liver during an inflammatory reaction. Since C-reactive protein levels in the blood rise more quickly after the inflammatory or infective process begins, ESR is often replaced with C-reactive protein measurement. There are specific drawbacks, however, as they were found to be independently associated with a diagnosis of acute maxillary sinusitis so that the combination of the two measurements improved diagnostic sensitivity and specificity.

The Test

How is it used?

The erythrocyte sedimentation rate (ESR) is an easy, inexpensive, nonspecific test that has been used for many years to help detect conditions associated with acute and chronic inflammation, including infections, cancers, and autoimmune diseases. ESR is said to be nonspecific because increased results do not tell the doctor exactly where the inflammation is in the body or what is causing it, and also because it can be affected by other conditions besides inflammation. For this reason, the ESR is typically used in conjunction with other tests.

ESR is helpful in diagnosing two specific inflammatory diseases, temporal arteritis and polymyalgia rheumatica. A high ESR is one of the main test results used to support the diagnosis. It is also used to monitor disease activity and response to therapy in both of these diseases.

When is it ordered?

An ESR may be ordered when a condition or disease is suspected of causing inflammation somewhere in the body. There are numerous inflammatory conditions that may be detected using this test. For example, it may be ordered when arthritis is suspected of causing inflammation and pain in the joints or when digestive symptoms are suspected to be caused by inflammatory bowel disease.

A physician may order an ESR test (along with other tests) to evaluate a patient who has symptoms that suggest polymyalgia rheumatica or temporal arteritis, such as headaches, neck or shoulder pain, pelvic pain, anemia, unexplained weight loss, and joint stiffness. There are many other conditions that can result in a temporary or sustained elevation in the ESR.

Before doing an extensive workup looking for disease, a doctor may want to repeat the ESR test after a period of several weeks or months. If a doctor already knows the patient has a disease like temporal arteritis (where changes in the ESR mirror those in the disease process), she may order the ESR at regular intervals to assist in monitoring the course of the disease. In the case of Hodgkin's disease, for example, a sustained elevation in ESR may be a predictor of an early relapse following chemotherapy.

What does the test result mean?

Since ESR is a nonspecific marker of inflammation and is affected by other factors, the results must be used along with the doctor's other clinical findings, the patient's health history, and results from other appropriate laboratory tests. If the ESR and clinical findings match, the doctor may be able to confirm or rule out a suspected diagnosis. A single elevated ESR, without any symptoms of a specific disease, will usually not give the physician enough information to make a medical decision. Furthermore, a normal result does not rule out inflammation or disease.

Moderately elevated ESR occurs with inflammation, but also with anemia, infection, pregnancy, and old age.

A very high ESR usually has an obvious cause, such as a marked increase in globulins that can be due to a severe infection. The doctor will use other follow-up tests, such as blood cultures, depending on the patient's symptoms. People with multiple myeloma or Waldenstrom's macroglobulinemia (tumors that make large amounts of immunoglobulins) typically have very high ESRs even if they don't have inflammation. As noted before, those with polymyalgia rheumatica or temporal arteritis may also have very high ESRs.

A rising ESR can mean an increase in inflammation or a poor response to a therapy; a decreasing ESR can mean a good response.

Although a low ESR is not usually a cause for concern, it can be seen with conditions that inhibit the normal sedimentation of RBCs, such as polycythemia, extreme leukocytosis, and some protein abnormalities. Some changes in red cell shape (such as sickle cells in sickle cell anemia) also lower the ESR.

Is there anything else I should know?

ESR and C-reactive protein (CRP) are both markers of inflammation. Generally, ESR does not change as rapidly as does CRP, either at the start of inflammation or as it goes away. CRP is not affected by as many other factors as is ESR, making it a better marker of inflammation. However, because ESR is an easily performed test, many doctors still use ESR as an initial test when they think a patient has inflammation.

If the ESR is elevated, it is typically a result of globulins or fibrinogens. Your doctor may then order a fibrinogen level (a clotting protein that is another marker of inflammation) and a serum protein electrophoresis to determine which of these (or both) is causing the elevated ESR.

Females tend to have a higher ESR, and menstruation and pregnancy can cause temporary elevations.

In a pediatric setting, the ESR test is used for the diagnosis and monitoring of children with rheumatoid arthritis or Kawasaki disease.

Drugs such as dextran, methyldopa, oral contraceptives, penicillamine procainamide, theophylline, and vitamin A can increase ESR, while aspirin, cortisone, and quinine may decrease it.

There is a commercial rapid test available that performs the ESR in 4 minutes by a centrifugal method. It is being used more widely to shorten waiting times for patients, particularly in the Emergency Department.

1.  Should everyone have an ESR done?

The ESR is not a specific test — it does not point to any one condition or disease — and can be affected by many different factors other than inflammation. As such, it is not recommended for use in screening people without symptoms or apparently healthy people.

2.  What other tests might my doctor order besides ESR?

Your doctor may order the CRP test as well as other general tests, such as a comprehensive metabolic panel or a CBC, at the same time as the ESR. Your doctor may also order additional tests based on your symptoms, such as the ANA (antinuclear antibody) and RF (rheumatoid factor) tests for symptoms of arthritis, as well as a fibrinogen or serum protein electrophoresis.

3.  What do changes in my ESR mean?

The ESR may indicate the presence or abatement of infection or inflammation. If you have a chronic inflammatory disease, the ESR may fluctuate with the degree of activity of your condition.

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