The erythrocyte sedimentation rate (ESR) is determined by filling a calibrated tube of standard diameter with anticoagulated whole blood and measuring the rate of red blood cell (RBC) sedimentation during a specified period, usually 1 hour. When the RBCs settle toward the bottom of the tube, they leave an increasingly large zone of clear plasma, which is the area measured. Most changes in RBC sedimentation rate are caused by alterations in plasma proteins, mainly fibrinogen, with a much smaller contribution from alpha-2 globulins. Fibrinogen increases 12-24 hours after onset of an acute inflammatory process or acute tissue injury. Many conditions cause abnormally great RBC sedimentation (rate of fall in the tube system). These include acute and chronic infection, tissue necrosis and infarction, well-established malignancy, rheumatoid-collagen diseases, abnormal serum proteins, and certain physiologic stress situations such as pregnancy or marked obesity. The ESR is frequently increased in patients with chronic renal failure, with or without dialysis. In one study, 75% had Westergren ESRs more than 30 mm/hour, and some had marked elevations. One study found elevated ESR in 50% of patients with symptomatic moderate or severe congestive heart failure, with elevation correlating directly with plasma fibrinogen valves. Low ESR was found in 106 of the patients and was associated with severe CHF. Marked elevation of the Westergren ESR (defined as a value > 100 mm/hour) was reported in one study to be caused by infectious diseases, neoplasia, noninfectious inflammatory conditions, and chronic renal disease. This degree of ESR abnormality was found in about 4% of patients who had ESR determined.

ESR determination has three major uses: (1) as an aid in detection and diagnosis of inflammatory conditions or to help exclude the possibility of such conditions, (2) as a means of following the activity, clinical course, or therapy of diseases with an inflammatory component, such as rheumatoid arthritis, acute rheumatic fever or acute glomerulonephritis, and (3) to demonstrate or confirm the presence of occult organic disease, either when the patient has symptoms but no definite physical or laboratory evidence of organic disease or when the patient is completely asymptomatic.

The ESR has three main limitations: (1) it is a very nonspecific test, (2) it is sometimes normal in diseases where usually it is abnormal, and (3) technical factors may considerably influence the results. The tubes must be absolutely vertical; even small degrees of tilt have great effect on degree of sedimentation. Most types of anemia falsely increase the ESR as determined by the Wintrobe method. The Wintrobe method may be “corrected” for anemia by using a nomogram, but this is not accurate. The Westergren method has a widespread reputation for being immune to the effects of anemia, but studies have shown that anemia does have a significant effect on the Westergren method (although not quite as much as the Wintrobe method). Although no well-accepted method is available to correct the Westergren ESR for effect of anemia, one report included a formula that is easy to use and provides a reasonable degree of correction: Corrected (Westergren) ESR = ESR – [(Std. Ht – Actual Ht) x 1.75], where Std. Ht (standard hematocrit) is 45 for males and 42 for females.

Besides anemia and changes in fibrinogen and alpha-2 globulins, other factors affect the ESR. Changes in serum proteins that alter plasma viscosity influence RBC sedimentation. A classic example is the marked increase in ESR seen with the abnormal globulins of myeloma. Certain diseases such as sickle cell anemia and polycythemia falsely decrease the ESR. The majority of (but not all) investigators report that normal values are age related; at least 10 mm/hour should be added to young adult values after age 60. Some use a formula for Westergren values: for men, age in years x 2; for women, (age in years + 10) x 2.