A. Characteristics
- Measures sedimentation of erythrocytes in plasma (anti-coagulated blood)
- May be increased in some disease processes and in pregnancy
- Often high in myeloproliferative disease: myeloma, macroglobulinemia, cryoglobulinemia
- Infection commonly increases
- Collagen vascular disease, especially with flares
- Erythrocyte pro-aggregrants include proteins relative potency:
- Fibrinogen 10X
- beta-globulin 5X
- alpha-globulin 2X
- gamma-globulin 2X
- Albumin 1X
- C-reactive protein 0X
- Westergren Method
- Venous blood is collected and
- Dilute 4:1 with Na citrate or EDTA (modified method)
- Place in 200mm glass tube (2.5mm internal diameter)
- Measure distance from meniscus to top of column after 1 hour.
- Utility
- ESR elevation is rarely the only indication of serious disease
- Elevated ESR without symptoms should generally not be further evaluated
- Useful in diagnosis temporal (giant cell) arteritis and polymyalgia rheumatica (PMR)
- May be used to follow response to therapy in the above and other diseases
- Elevation >100mm/hr is fairly specific for serious conditions
- In general, C-reactive protein (CRP) is a more objective measure of inflammation [2]
- IL6-driven gene expressed in liver
- General marker for inflammation
- Elevated CRP level carries a 1.5 fold increased risk for coronary artery disease (CAD) [3]
- CRP is the strongest independent nonlipid predictor of systemic atherosclerosis [4]
- Elevations of CRP and ESR in patients with chest pain and normal Troponin T arries a
- 5-7.5X fold increased risk of CV events at 6 months [5]
B. Differential Diagnosis ESR Changes
- ESR > 100mm/hr
- Infection: subacute bacterial endocarditis, osteomyelitis, abscess, Tuberculosis
- Cancers: lymphomas, myeloma, renal cell cancers, other myeloproliferative disease
- Vasculitis: Temporal Arteritis, ANCA+ disease flares, Polymyalgia Rheumatica (PMR)
- Severe systemic lupus erythematosus (particularly with renal disease)
- ESR Elevation
- Infection (Tuberculosis, acute viral hepatitis)
- Tissue Necrosis especially Neoplasms (lymphoma, mammary, colon cancer)
- Acute MI (inflammatory response) and acute coronary syndromes [5]
- Low Serum Albumin, Elevated Serum Globulins
- Arsenic and lead intoxication
- Multiple Myeloma (high IL6, acute phase reactant, positively charged Igs)
- Nephrosis, renal disease with azotemia
- Pregnancy
- Very Low ESR
- Sickle Cell Anemia
- Polycythemia
- Hyperviscosity syndrome
- Macroglobulinemia
- Congestive Heart Failure
- Multiple myeloma (high globulin fraction, negatively charged immunoglobulins)
C. Acute Phase Proteins
- A number of proteins whose serum levels increase with inflammation have been found
- These are called acute phase reactants or proteins (APR)
- Interleukin 6 (IL-6) is the chief stimulator of most acute phase proteins
- Interleukin 1ß (IL-1ß) can also stimulate many of the acute phase proteins
- IL-6 related proteins IL-11, LIF, oncostatin M, ciliary neurotrophic factor may have similar activity to IL-6
- Glucocorticoids generally enhance the effects of cytokines on APP
- Some ARP levels go down with inflammation
- The following APR levels increase with inflammation [2,6]:
- Fibrinogen
- Plasminogen
- Tissue plasminogen activator (TPA)
- Plasminogen activator inhibitor 1 (PAI-1)
- Urokinase
- Protein S
- Vitronectin
- C-Reactive Protein (CRP)
- Serum Amyloid A - chronically high levels cause amyloidosis
- Haptoglobin
- alpha1-Acid Glycoprotein
- Fibronectin
- Ceruloplasmin
- Haptoglobin (moreso than hemopexin)
- Ferritin
- Complement Proteins C3, C4 and C9
- Complement C1 Esterase Inhibitor
- Complement C4b Binding Protein
- Complement Factor B
- Mannose binding protein (lectin)
- alpha1-antichymotrpsin
- Pancreatic secretory trypsin inhibitor
- alpha1-Protease Inhibitor
- alpha2-Macroglobulin
- Phospholipase A2
- Pancreatic secretory trypsin inhibitor aa. Inter-alpha protease inhibitor
- The following ARP levels decrease with inflammation [2,6]:
- Albumin
- Transthyretin (Prealbumin)
- Transferrin
- alpha2-HS Glycoprotein
- alpha-fetoprotein (AFP)
- Thyroxine binding globulin
- IGF-1
- Clotting Factor XII
References
- Brigden M. 1998. Postgrad Med. 103(5): 257
- Gabay C and Kushner I. 1999. NEJM. 340(6):448
- Ridker PM, Hennekens CH, Buring JE, Rifai N. 2000. NEJM. 342(12):836
- Ridker PM, Stampfer MJ, Rifai N. 2001. JAMA. 285(19):2481
- Bholasingh R, Cornel JH, Kamp O, et al. 2003. Am J Med. 115(7):521
- Mackowiak PA. 1998. Arch Intern Med. 158(17):1870