†††† The erythrocyte sedimentation rate (ESR) is a test which measures the height of the layer of red blood cells which precipitate and layer in a tube of anticoagulated blood over a specified length of time which is usually one hour.† Two main factors determine the ESR, the degree of cellular aggregation and the hematocrit.† Aggregation is influenced by the concentration of plasma proteins (acute phase reactants) which serve to reduce the negative electrostatic forces between red blood cells and thus enhance aggregation which leads to faster sedimentation.† The test is not very sensitive or specific, but is often used clinically as a marker of underlying inflammation.† The C reactive protein (CRP) is another test used for this purpose but requires more time, equipment and expense.

†††† The normal range for the ESR is 15 mm/hr or less in males and 20 mm/hr or less in females when the patientís age is less than or equal to 50 years.† For males over 50 years of age the upper limit of normal is (age in years)/2 and for females over 50 years of age, (age in years + 10)/2.† Certain medications (NSAIDs and steroids) may lower the ESR.† Several medical conditions may be associated with an excessively low ESR, but most patients with a low ESR and no symptoms do not require further evaluation.† It is of note that when the ESR is elevated in conjunction with a low CRP, a search for a plasma cell dyscrasia (multiple myeloma or macroglobulinemia) should be initiated.

†††† Aspirin therapy may have a variable effect on the ESR, in some cases causing an elevation in the value while in others causing a falsely low value.† Medications known to cause a false elevation on the ESR include anticonvulsants, dexamethasone, hydralazine HCl, oral contraceptives, procainamide, sulfamethoxazole, theophylline, and beta carotene.† Medications associated with a falsely depressed ESR include cortisone acetate, cyclophosphamide, methotrexate, NSAIDs, prednisone, tamoxifen, and trimethoprim.

†††† The ESR is spuriously elevated when there is underlying severe anemia.† Also, the size of the red blood cells will affect the ESR, with macrocytes settling more quickly (increased ESR) and microcytes more slowly (normal or depressed ESR).† The abnormal shape of erythrocytes in sickle cell disease interferes with rouleau formation and spuriously decreases the ESR.† In fact, a low ESR is so common in conjunction with sickle cell disease that a sickle cell patient with an elevated ESR should be suspected of an occult infection, particularly osteomyelitis.

†††† An elevated ESR is generally considered a very nonspecific marker for underlying inflammation; however, a markedly elevated value with the appropriate symptoms is indicative of either temporal arteritis or polymyalgia rheumatica.† In both these conditions a markedly elevated ESR is generally encountered but a normal value in the face of physical symptoms does not exclude the diagnosis.† A mildly elevated ESR in an asymptomatic patient should merely be repeated after several months (consider silent local infections such as gingivitis, sinusitis, urinary tract infection, etc); however, a markedly elevated ESR should prompt a search for a more severe infectious etiology (endocarditis, tuberculosis), collagen vascular disorders (rheumatoid arthritis, vasculitis, etc.), and malignant tumors with metastasis.† The evaluation of an asymptomatic patient with a markedly elevated ESR in excess of 100 mm/hr should include: CBC, BUN/Cr, PPD testing, serum and urine protein electrophoresis, urinalysis, serum liver function studies, stool hemoccult testing and chest radiography.

†††† Another situation in which the ESR is useful is in correcting the acceptable lower limit of the ferritin value in patients with suspected iron deficiency anemia and underlying inflammation.† In this instance the underlying inflammation will be accompanied by an increase in acute phase reactants, of which ferritin is one.† Therefore, the distinction between iron deficiency anemia and anemia of chronic disease in a patient with a microcytic anemia, a low retic count and underlying inflammation is difficult as the ferritin may be spuriously elevated.† In this instance a ferritin greater than 80 ng/mL makes iron deficiency unlikely.† However, if the ferritin is less than 80 ng/mL the acceptable lower limit of normal may be corrected using the ESR via the following equation:

†††††††††††††††††††††††††††††††† ESR/2 + 5 = corrected lower limit of normal for ferritin.

If the actual serum ferritin value is greater than the above corrected value, iron deficiency is unlikely.† However, if the actual serum value is less than the above corrected value, iron deficiency is still a possible etiology for the patientís anemia.