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Erythrocyte Sedimentation Rate (ESR)

The Westergren ESR is a measurement of the distance in millimeters that red blood cells (RBCs) fall within a specified tube over 1 hour. The ESR is an indirect measurement of alterations in acute-phase reactants and quantitative immunoglobulins. Acute-phase reactants are a heterogeneous group of proteins (fibrinogen, haptoglobin, C-reactive protein, alpha-1-antitrypsin, and others) that are synthesized in the liver in response to inflammation. Interleukin-6 (IL-6), an inflammatory cytokine, is an important mediator that stimulates the production of acute-phase reactants. Any condition that causes either a rise in the concentration of these asymmetrically charged acute-phase proteins or hypergammaglobulinemia (polyclonal or monoclonal) will cause an elevation of the ESR by increasing the dielectric constant of the plasma. This dissipates inter-RBC repulsive forces, and leads to closer aggregation of RBCs (i.e., rouleaux formation), which causes them to fall faster, increasing the result of the ESR. Aging, female sex, obesity, pregnancy, and possibly race are noninflammatory conditions that can elevate the sedimentation rate. Alterations in number, size, or shape of erythrocytes may physically interfere with rouleaux formation affecting the ESR. Normal ranges of values therefore vary with patient characteristics.

A rough rule of thumb for the age-adjusted upper limit of normal for ESR (mm/h) is:

Male=age/2; Female=(age+10)/2

Causes of extremely high or extremely low ESR:

  • Markedly elevated ESR (>100 mm/h)
    • Infection, bacterial (35%)
    • Connective tissue disease: giant cell arteritis, polymyalgia rheumatica, SLE, other vasculitides (25%)
    • Malignancy: lymphomas, myeloma, others (15%)
    • Other causes (25%)
  • Markedly low ESR (0 mm/h)
    • Afibrinogenemia/dysfibrinogenemia
    • Agammaglobulinemia
    • Extreme polycythemia (hematocrit >65%)
    • Increased plasma viscosity

Approach to the evaluation of elevated ESR:

  • Complete history and physical examination and routine screening laboratories (complete blood count, chemistries, liver enzymes, urinalysis). Make sure that routine health care maintenance is up-to-date. Repeat ESR to ensure it is still elevated and there was no laboratory error.

  • If there is no clear association after step a, consider the following:

  • Review the medical record to compare with any previously obtained ESR data to determine how long the ESR may have been elevated.

  • Check SPEP, fibrinogen, and CRP for evidence of acute-phase response, as well as to rule out myeloma or polyclonal gammopathy.

  • If still no obvious explanation, recheck the ESR in 1–3 months. Up to 80% of patients will normalize. Follow patient for development of other symptoms or signs of disease if ESR remains elevated.


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