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Normal values:
ESR values tend to rise with age and are generally higher in women. ESR is also elevated in the
African - American population.
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 are:
o Newborn: 0 to 2 mm/hr
o Neonatal to puberty: 3 to 13 mm/hr, but other laboratories place an upper limit of 20.
o Men: 3-9 mm/h
o Women: 6-12 mm/h
o Alert values: > 50 mm/h
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 aggregate 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.
Fig. 2. Rouleaux
2
Any condition that elevates fibrinogen (e.g., pregnancy, diabetes mellitus, end-stage renal
failure, heart disease, collagen vascular diseases, malignancy) may also elevate the ESR.
Anemia and macrocytosis increase the ESR. In anemia, with the hematocrit reduced, the
velocity of the upward flow of plasma is altered so that red blood cell aggregates fall faster. Macrocytic
red cells with a smaller surface-to-volume ratio also settle more rapidly.
Some conditions with very high (>100 mm/hr) ESR:
Malignancies e.g. multiple myeloma
Connective tissue disorders - autoimmune diseases
Tuberculosis
Severe anemia
A decreased ESR is associated with a number of blood diseases in which red blood cells have an
irregular or smaller shape that causes slower settling.
In patients with polycythemia, too many red blood cells decrease the compactness of the rouleau
network and artifactually lower the ESR.
Some conditions with low ESR:
Polycythemia
Severe leukocytosis
Sickle cell disease (anemia)
Hereditary spherocytosis
Hypofibrinogenemia
Corticosteroid use
2. Acute-phase proteins
Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acutephase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response
is called the acute-phase reaction (also called acute-phase response).
In response to injury, local inflammatory cells (neutrophil granulocytes and macrophages) secrete a
number of cytokines into the bloodstream, most notable of which are the interleukins IL-1, IL-6 and
IL-8, and TNF-.
The liver responds by producing a large number of acute-phase reactants. At the same time, the
production of a number of other proteins is reduced; these are, therefore, referred to as "negative"
acute-phase reactants.
Positive" acute-phase proteins:
C-reactive protein
Alpha 1-antitrypsin
Alpha 1-antichymotrypsin
Ferritin
Ceruloplasmin
Haptoglobin
Fibrinogen
Low levels of fibrinogen can indicate a systemic activation of the clotting system, with
consumption of clotting factors faster than synthesis. This excessive clotting factor
consumption condition is known as disseminated intravascular coagulation.
Figure 5. Neutrophilia