Basics:
The ESR test in performed in the laboratory by placing anticoagulated blood in an upright tube (Westegren's most often). At the end of an hour of this, the rate of the RBC sedimentation is measured.

Normal value:
ESR values tend to rise with age and are generally higher in women. ESR is also elevated in the black population and those with anemia.
A rule of thumb for calculating maximum normal ESR in a person is:

At birth, the ESR is generally low, 1-2 mm/hr, rising to up to 20 mm/hr by puberty.
Mechanism:
ESR is determined by the interaction between factors that promote (fibrinogen) and resist (negative charge of RBCs - that repel each other) sedimentation. Normal RBCs settle slowly as they do not form rouleaux or aggragate together. Instead, they gently repel each other due to the negative charge on their surfaces.
Increased rouleaux formation contributes to high ESR. Rouleaux are stacks of many RBCs that become heavier and sediment faster. Plasma proteins, especially fibrinogen, adhere to the red cell membranes and neutralize the surface negative charges, promoting cell adherence and rouleaux formation.

The aggregated RBCs in the rouleaux formation have a higher ratio of 'mass to surface area' as compared to single RBCs and hence sink faster in plasma.
ESR of more than 100 mm/hr is strongly associated with serious underlying disorders like connective tissue disease, infections and malignancies.
Some conditions with very high (>100 mm/hr) ESR:
- Multiple myeloma
- Connective tissue disorders - SLE, RA and other autoimmune diseases
- Tuberculosis
- Malignancies
- Severe anemia
Some conditions with low ESR:
- Polycythemia
- Severe Leukocytosis
- Sickle cell disease (anemia)
- Hereditary spherocytosis
- Congestive cardiac failure
- Corticosteroid use
- Hypofibrinogenemia
Note that sickle cell anemia and spherocytosis have low ESR unlike other anemias. This is due to reduced rouleaux formation owing to the abnormally shaped RBCs in this condition.
IMPORTANT
Erythrocyte sedimentation rate is a non-specific test and is not diagnostic of any particular disease. It has a high sensitivity but low specificity. Never base a diagnosis solely on an ESR value, either normal or high. Interpretation of the result should always be along with the patient's clinical history, examination findings and results of other tests done.
If high ESR is encountered without any obvious reasons, patient should be reassured and the test repeated after a reasonable amount of time (a couple of months). There is no need to extensively search for an occult disease without repeating it again.




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