The erythrocyte sedimentation rate (ESR) represents the rate (space/time) at which red blood cells sediment in the blood sample after collection in a tube with anticoagulant. It is expressed in millimeters of sediment produced in 1 hour.
Under physiological conditions, red blood cells in sus pension sediment little if they remain separated from each other. In contrast, if they aggregate and form cellular clusters, they sediment much more quickly. The aggregation of red blood cells is hindered by the electrical charges of their membranes and favored by inflammation proteins. The negative charge of the red blood cell surface causes erythrocytes to repel each other; however, this negative charge can be neutralized by positively charged plasma proteins, which therefore promote erythrocyte aggregation. Thus, ESR is regulated by the balance between pro-sedimentation factors (proteins, in particular, fibrinogen, CRP, IgM, and alpha 1- macroglobulin) and anti-sedimentation factors (negative membrane charge of erythrocytes). The aggregates that form are called rouleaux and consist of erythrocytes stacked on each other. The sedimentation process occurs in three stages:
1. Formation of rouleaux
2. Aggregation of rouleaux which tend to settle
3. Acceleration of sedimentation, with the accumulation of the rouleaux at the bottom of the tube
ESR indirectly indicates the degree of inflammation.
Generally, ESR is determined by quantitative capillary photometry and the value is obtained by dynamic measurement of the formation process of erythrocyte clusters.
ESR is a laboratory test commonly ordered in clinical practice but is highly nonspecific. ESR can increase in numerous pathological conditions. Moreover, the ESR value is not proportional to the extent and severity of the disease and its course. Finally, a negative ESR value does not rule out any disease. ESR is in great demand in clinical practice and represents a first-level test because its determination is easy to perform, is inexpensive, and provides a general indication of an inflammatory alteration. In clinical practice, high ESR values represents an “alarm signal” that should lead to more in-depth investigations.
Reference ESR values are reported in Table 1; since women and the elderly tend to have higher ESR values, these should be differentiated according to age and sex.

Table1. Normal values of erythrocyte sedimentation rate (ESR)
Table 2 shows the main pathological conditions associated with altered ESR values.

Table2. Conditions associated with altered erythrocyte sedimentation rate values