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A. Characteristicsnavigator

  1. Measures sedimentation of erythrocytes in plasma (anti-coagulated blood)
  2. May be increased in some disease processes and in pregnancy
    1. Often high in myeloproliferative disease: myeloma, macroglobulinemia, cryoglobulinemia
    2. Infection commonly increases
    3. Collagen vascular disease, especially with flares
  3. Erythrocyte pro-aggregrants include proteins relative potency:
    1. Fibrinogen 10X
    2. beta-globulin 5X
    3. alpha-globulin 2X
    4. gamma-globulin 2X
    5. Albumin 1X
    6. C-reactive protein 0X
  4. Westergren Method
    1. Venous blood is collected and
    2. Dilute 4:1 with Na citrate or EDTA (modified method)
    3. Place in 200mm glass tube (2.5mm internal diameter)
    4. Measure distance from meniscus to top of column after 1 hour.
  5. Utility
    1. ESR elevation is rarely the only indication of serious disease
    2. Elevated ESR without symptoms should generally not be further evaluated
    3. Useful in diagnosis temporal (giant cell) arteritis and polymyalgia rheumatica (PMR)
    4. May be used to follow response to therapy in the above and other diseases
    5. Elevation >100mm/hr is fairly specific for serious conditions
  6. In general, C-reactive protein (CRP) is a more objective measure of inflammation [2]
    1. IL6-driven gene expressed in liver
    2. General marker for inflammation
    3. Elevated CRP level carries a 1.5 fold increased risk for coronary artery disease (CAD) [3]
    4. CRP is the strongest independent nonlipid predictor of systemic atherosclerosis [4]
    5. Elevations of CRP and ESR in patients with chest pain and normal Troponin T arries a
  7. 5-7.5X fold increased risk of CV events at 6 months [5]

B. Differential Diagnosis ESR Changesnavigator

  1. ESR > 100mm/hr
    1. Infection: subacute bacterial endocarditis, osteomyelitis, abscess, Tuberculosis
    2. Cancers: lymphomas, myeloma, renal cell cancers, other myeloproliferative disease
    3. Vasculitis: Temporal Arteritis, ANCA+ disease flares, Polymyalgia Rheumatica (PMR)
    4. Severe systemic lupus erythematosus (particularly with renal disease)
  2. ESR Elevation
    1. Infection (Tuberculosis, acute viral hepatitis)
    2. Tissue Necrosis especially Neoplasms (lymphoma, mammary, colon cancer)
    3. Acute MI (inflammatory response) and acute coronary syndromes [5]
    4. Low Serum Albumin, Elevated Serum Globulins
    5. Arsenic and lead intoxication
    6. Multiple Myeloma (high IL6, acute phase reactant, positively charged Igs)
    7. Nephrosis, renal disease with azotemia
    8. Pregnancy
  3. Very Low ESR
    1. Sickle Cell Anemia
    2. Polycythemia
    3. Hyperviscosity syndrome
    4. Macroglobulinemia
    5. Congestive Heart Failure
    6. Multiple myeloma (high globulin fraction, negatively charged immunoglobulins)

C. Acute Phase Proteinsnavigator

  1. A number of proteins whose serum levels increase with inflammation have been found
  2. These are called acute phase reactants or proteins (APR)
    1. Interleukin 6 (IL-6) is the chief stimulator of most acute phase proteins
    2. Interleukin 1ß (IL-1ß) can also stimulate many of the acute phase proteins
    3. IL-6 related proteins IL-11, LIF, oncostatin M, ciliary neurotrophic factor may have similar activity to IL-6
    4. Glucocorticoids generally enhance the effects of cytokines on APP
  3. Some ARP levels go down with inflammation
  4. The following APR levels increase with inflammation [2,6]:
    1. Fibrinogen
    2. Plasminogen
    3. Tissue plasminogen activator (TPA)
    4. Plasminogen activator inhibitor 1 (PAI-1)
    5. Urokinase
    6. Protein S
    7. Vitronectin
    8. C-Reactive Protein (CRP)
    9. Serum Amyloid A - chronically high levels cause amyloidosis
    10. Haptoglobin
    11. alpha1-Acid Glycoprotein
    12. Fibronectin
    13. Ceruloplasmin
    14. Haptoglobin (moreso than hemopexin)
    15. Ferritin
    16. Complement Proteins C3, C4 and C9
    17. Complement C1 Esterase Inhibitor
    18. Complement C4b Binding Protein
    19. Complement Factor B
    20. Mannose binding protein (lectin)
    21. alpha1-antichymotrpsin
    22. Pancreatic secretory trypsin inhibitor
    23. alpha1-Protease Inhibitor
    24. alpha2-Macroglobulin
    25. Phospholipase A2
    26. Pancreatic secretory trypsin inhibitor aa. Inter-alpha protease inhibitor
  5. The following ARP levels decrease with inflammation [2,6]:
    1. Albumin
    2. Transthyretin (Prealbumin)
    3. Transferrin
    4. alpha2-HS Glycoprotein
    5. alpha-fetoprotein (AFP)
    6. Thyroxine binding globulin
    7. IGF-1
    8. Clotting Factor XII


References navigator

  1. Brigden M. 1998. Postgrad Med. 103(5): 257 abstract
  2. Gabay C and Kushner I. 1999. NEJM. 340(6):448 abstract
  3. Ridker PM, Hennekens CH, Buring JE, Rifai N. 2000. NEJM. 342(12):836 abstract
  4. Ridker PM, Stampfer MJ, Rifai N. 2001. JAMA. 285(19):2481 abstract
  5. Bholasingh R, Cornel JH, Kamp O, et al. 2003. Am J Med. 115(7):521 abstract
  6. Mackowiak PA. 1998. Arch Intern Med. 158(17):1870 abstract