What Does a High Esr Level Mean

The erythrocyte sedimentation rate (ESR) blood test checks for chronic inflammation, but it's not sensitive. Often called the "sickness index," doctors can also use it to track the progress of specific diseases. Read on to find out how ESR works, what can impact ESR levels in your body, and how this lab marker relates to your health.

What Is the Erythrocyte Sedimentation Rate (ESR)?

Definition

Erythrocyte sedimentation rate (ESR) was discovered in 1987 [1, 2].

The ESR is the rate at which red blood cells (erythrocytes) sink to the bottom (sedimentation) of a tube in one hour [3, 4].

The main factors affecting ESR are hematocrit (percentage of red blood cells in your blood) and blood proteins, such as fibrinogen [5].

Erythrocyte Sedimentation Rate (ESR) Blood Test

Erythrocyte sedimentation rate (ESR) test or "sed rate test", is a blood test that checks for inflammation. It measures the distance in millimeters that red blood cells fall in one hour (mm/hr) [6, 7].

There are a few ways that this is measured, such as the Westergren method, Wintrobe Method, MicroESR, and automated methods [8, 9, 10].

Westergren Method

The Westergren method is considered the gold standard in measuring ESR [11].

The blood sample is mixed with sodium citrate (4:1). Then it is mixed into a Westergren-Katz tube (2.5 mm diameter) until the 200 mm mark.

Next, the tube is set vertically, at room temperature (18 – 25 °C), for one hour.

At the end of an hour, they measure how far the red blood cells have settled. This distance is ESR.

In the modified Westergren method, edetic acid is used instead of sodium citrate [8, 9, 10].

Other Methods

The Wintrobe method is less sensitive than the Westergren method and the maximal values may be misleading [12, 13].

The micro ESR method is quick (20 min) and popular for babies, as the test requires very little blood. It is also useful for diagnosing neonatal sepsis [14, 15, 16].

Automated methods are faster, easy to use, and could be better predictors for autoimmune diseases. Yet, their sensitivity to technical procedures (blood mixing, tube sizes, etc.) could influence the test results [17, 18, 19, 20, 21, 22, 23, 24].

ESR is most commonly measured using the Westergren method. Micro ESR can be used in newborns and it requires only a small amount of blood.

When to Get a Sed Rate Test

Your doctor may order an ESR test if you have the following symptoms [25]:

Headache
Fever
Joint or shoulder pain
Abnormal weight loss
Anemia

What Can The ESR Test Reveal?

Factors and disease shown here are commonly associated with abnormal ESR values. Work with your doctor or other health care professional for an accurate diagnosis.

1) Inflammation

The ESR test checks if you have an inflammation [3].

In inflammation, certain proteins will appear in the blood, such as fibrinogen. These proteins cause red blood cells to cling together and form clumps. This makes them heavier, so they fall faster, which increases the ESR [5, 26, 3].

Therefore, high ESR shows inflammation. The higher the ESR level, the higher the inflammation [5, 26, 3].

But, the ESR test is not very sensitive (so it can't pick up all inflammation) nor specific, so it can not diagnose specific diseases [6].

2) Screening for Specific Diseases

The ESR test could help with the diagnosis of certain diseases:

Polymyalgia rheumatica (an inflammatory disease which causes muscle pain and stiffness) [27, 28, 29]
Giant cell arteritis (inflammation of blood vessels) [30, 31, 32, 33, 34]
Cancer [35, 36]
Bone infections [37, 38, 39]
Subacute thyroiditis (inflammation of the thyroid) [40, 41, 42]
Ulcerative colitis [43]

3) Progression of Specific Conditions

The ESR test cannot diagnose diseases, but it can track the progress of specific conditions [44]:

Heart disease [45, 46, 47]
Cancer [48, 5, 49]
Rheumatoid arthritis [50, 51, 52]
Systemic lupus erythematosus (SLE) [53, 54]
Sickle-cell disease [55, 56, 57]

4) Serious Conditions

ESR levels higher than 100 mm/hr could suggest a serious disease, such as infection, heart disease, or cancer [58, 5, 3, 6].

ESR levels higher than normal may predict cancer or cancer progression, like metastasis [59, 60, 61, 62, 63].

Your doctor may order an ESR test to check for specific inflammatory or chronic conditions, along with other tests. ESR is considered a non-specific, non-sensitive marker of chronic inflammation.

Normal ESR Levels

Age	Men	Women
Younger than 50	0-15 mm	0-20 mm
Older than 50	0-20 mm	0-30 mm

Children should have an ESR lower than 10mm [3].

A low ESR is normal and does not cause any symptoms [25].

Factors That Increase ESR Levels

Disorders and diseases:

Inflammation, infection, or malignant diseases can increase ESR rates [3, 5, 26, 64, 65, 66]
Women tend to have higher ESR rates [3, 6, 5, 67]
Old age [3, 6, 5, 67, 68]
Anemia; reduced hematocrit increases ESR levels [3, 5, 6, 65]
Macrocytosis (large red blood cells) [3, 5]
Polycythemia (increased production of red blood cells) [3, 5, 69, 8, 70]
Increased fibrinogen levels [3, 5]
Pregnancy [71, 72]
Diabetes [3, 5, 73]
Kidney failure [74]
Chronic heart failure [75]
Obesity [6, 5]
Hyperlipidemia (high concentrations of fats in the blood) [76]
Heart disease [77, 45, 46]
Polymyalgia rheumatica (an inflammatory disorder where there is muscle pain around the shoulders and hips) [78, 28, 79]
Subacute thyroiditis [40]
Alcoholic liver disease, which can cause decreased albumin production, and thus increase ESR [80]
Crohn's disease and ulcerative colitis [81, 82]
Kidney failure [74]
Temporal/giant cell arteritis (inflammation in blood cells around the scalp) [83, 84]
Multiple myeloma [85]
Waldenstrom's macroglobulinemia (tumors that make large amounts of immunoglobulins) [86, 87]
Atherosclerosis (plaque buildup in the arteries) and stroke [88]
Cancer risk, progression, and death [35, 89, 90]

Many inflammatory disorders and chronic diseases are associated with high ESR values.

Drugs and supplements:

Iodine, when it causes thyroid problems [91]
High ginger consumption, when it's linked to subacute thyroiditis [92]
Birth control [93]
Smoking [94, 95, 96, 97]
Alcohol [80, 98]
Dextran [99]

Technical errors during the test such as a tilted tube or dilution error can also give a false high ESR result [3].

Factors That Decrease ESR Levels

When red blood cells are smaller, they will drop slower, hence a lower ESR.

Red blood cells diseases: extreme leukocytosis, polycythemia, microcytosis, sickle cell disease, spherocytosis, acanthocytosis, and anisocytosis [3, 5, 69, 8, 55]
Protein abnormalities: hypofibrinogenemia, hypogammaglobulinemia, and dysproteinemia with hyperviscosity state [3, 5, 8, 65, 100, 70]
NSAIDs, cortisone, anesthetic drugs, levamisole, and prednisone [101, 5, 8, 102, 84]

Low ESR is usually normal, but some factors that excessively lower red blood cells have also been linked to low ESR values.

ESR Genetics

Genes That Affect ESR

These SNPs/genes are associated with a higher ESR:

rs3750996 (G/G) [103], rs3750996 (G-C) [103]
rs2066865 (C>T) (minor allele) [104]
rs3750994 (G-C) is related to higher ESR levels [103]

High fibrinogen levels make the red blood cells heavier and increase the ESR. So, genes increasing fibrinogen production could theoretically increase ESR levels. These include:

rs2070006 (T>C) [105]
rs2070011 (T>C) [105, 106]
rs6050 (G>A) (major allele) [107, 108]
rs1800790 (G>A) (minor allele) [107, 109, 110, 105]
rs1800791 (G>A) [111, 106]
rs2227399 (G>T) [105]
rs4220 (G>A) [105, 106]
rs7439150 (G>A) [111, 112]
rs1049636 (T>C) [111, 106]

These SNPs/genes are associated with lower ESR levels:

rs630337 (T/C) [113]
rs11117956 (T/G) [113]
rs11549407 (A/G) [113]
rs650877 (G/A) [114]
rs11118131 (T/C) [114]
rs677066 (G/A) [114]
rs6691117 (G/A) [114]
rs12034383 (G/A) [114]
rs1043879 [114]
rs3091242 [114]
rs873308 [114]
rs10903129 [114]
rs7527798 [114]

Low fibrinogen levels make the red blood cells lighter and decrease the ESR. So, genes decreasing fibrinogen production may theoretically reduce ESR levels:

rs1800787 (C>T) is associated with low fibrinogen, slow initiation of the coagulation cascade, and possibly childhood pneumonia [106, 115].
rs148685782 (G>C) is associated with low blood fibrinogen levels and hypofibrinogenemia [116, 117].

ESR and C-Reactive Protein (CRP)

In inflammation, the liver is producing a protein called C-reactive protein (CRP). The CRP blood test checks whether you have inflammation or infection. CRP levels higher than 10 mg/dL show infection [118, 119, 120].

CRP test is used most times together with the ESR test [121, 122, 123].

C-reactive protein is more sensitive than ESR and produces less false negative/false positive results than ESR [25].

CRP is better for checking and tracking the progress of acute inflammations, and infections [25, 121, 122].

ESR is better for checking and tracking the progress of chronic inflammations, and infections [25, 121, 122].

Both ESR and CRP can increase with inflammation, but CRP may be a better marker of acute and ESR of chronic inflammation and infection.

Limitations and Caveats

While there are many studies examining ESR, almost all of them are population-based, which means they can associate high or low ESR values with certain conditions but not establish them as their cause. Additional limitations of some of these studies include being based on older data or only conducted with men.

More clinical trials investigating ESR should be undertaken.

Takeaway

Erythrocyte sedimentation rate (ESR) test or "sed rate test" is a blood test that checks for inflammation.

It is most commonly measured using the Westergren method, the gold standard in assessing ESR. Micro ESR is another method that can be used in newborns that requires only a small amount of blood.

Your doctor may order an ESR test if you show signs or symptoms of infection or inflammation, such as fever, headache, and pain. They may also order this test to screen for specific diseases or to monitor chronic autoimmune diseases like lupus and rheumatoid arthritis.

The normal ESR range should be below 15 or 30 mm, depending on gender and age.