Reference ranges (reference intervals) for blood tests are sets of values used by a health professional to interpret a set of medical test results from blood samples. Reference ranges for blood tests are studied within the field of clinical chemistry (also known as "clinical biochemistry", "chemical pathology" or "pure blood chemistry"), the area of pathology that is generally concerned with analysis of bodily fluids.[1][2][3]
Blood test results should always be interpreted using the reference range provided by the laboratory that performed the test.[4]
Interpretation
A reference range is usually defined as the set of values 95 percent of the normal population falls within (that is, 95% prediction interval).[5] It is determined by collecting data from vast numbers of laboratory tests.[6][7]
Plasma or whole blood
In this article, all values (except the ones listed below) denote blood plasma concentration, which is approximately 60–100% larger than the actual blood concentration if the amount inside red blood cells (RBCs) is negligible. The precise factor depends on hematocrit as well as amount inside RBCs. Exceptions are mainly those values that denote total blood concentration, and in this article they are:[8]
All values in Hematology – red blood cells (except hemoglobin in plasma)
Mass concentration (g/dL or g/L) is the most common measurement unit in the United States. Is usually given with dL (decilitres) as the denominator in the United States, and usually with L (litres) in, for example, Sweden.[citation needed]
Molar concentration (mol/L) is used to a higher degree in most of the rest of the world, including the United Kingdom and other parts of Europe and Australia and New Zealand.[9]
If not otherwise specified, a reference range for a blood test is generally the venous range, as the standard process of obtaining a sample is by venipuncture. An exception is for acid–base and blood gases, which are generally given for arterial blood.[12]
Still, the blood values are approximately equal between the arterial and venous sides for most substances, with the exception of acid–base, blood gases and drugs (used in therapeutic drug monitoring (TDM) assays).[13] Arterial levels for drugs are generally higher than venous levels because of extraction while passing through tissues.[13]
Usual or optimal
Reference ranges are usually given as what are the usual (or normal) values found in the population, more specifically the prediction interval that 95% of the population fall into. This may also be called standard range. In contrast, optimal (health) range or therapeutic target is a reference range or limit that is based on concentrations or levels that are associated with optimal health or minimal risk of related complications and diseases. For most substances presented, the optimal levels are the ones normally found in the population as well. More specifically, optimal levels are generally close to a central tendency of the values found in the population. However, usual and optimal levels may differ substantially, most notably among vitamins and blood lipids, so these tables give limits on both standard and optimal (or target) ranges. In addition, some values, including troponin I and brain natriuretic peptide, are given as the estimated appropriate cutoffs to distinguish healthy people from people with specific conditions, which here are myocardial infarction and congestive heart failure, respectively, for the aforementioned substances.[14][15][16]
References range may vary with age, sex, race, pregnancy,[17] diet, use of prescribed or herbal drugs and stress. Reference ranges often depend on the analytical method used, for reasons such as inaccuracy, lack of standardisation, lack of certified reference material and differing antibody reactivity.[18] Also, reference ranges may be inaccurate when the reference groups used to establish the ranges are small.[19]
Hormones predominate at the left part of the scale, shown with a red at ng/L or pmol/L, being in very low concentration. There appears to be the greatest cluster of substances in the yellow part (μg/L or nmol/L), becoming sparser in the green part (mg/L or μmol/L). However, there is another cluster containing many metabolic substances like cholesterol and glucose at the limit with the blue part (g/L or mmol/L).[citation needed]
The unit conversions of substance concentrations from the molar to the mass concentration scale above are made as follows:
Numerically:
Measured directly in distance on the scales:
,
where distance is the direct (not logarithmic) distance in number of decades or "octaves" to the right the mass concentration is found. To translate from mass to molar concentration, the dividend (molar mass and the divisor (1000) in the division change places, or, alternatively, distance to right is changed to distance to left. Substances with a molar mass around 1000g/mol (e.g. thyroxine) are almost vertically aligned in the mass and molar images. Adrenocorticotropic hormone, on the other hand, with a molar mass of 4540,[20] is 0.7 decades to the right in the mass image. Substances with molar mass below 1000g/mol (e.g. electrolytes and metabolites) would have "negative" distance, that is, masses deviating to the left.
Many substances given in mass concentration are not given in molar amount because they haven't been added to the article.
The diagram above can also be used as an alternative way to convert any substance concentration (not only the normal or optimal ones) from molar to mass units and vice versa for those substances appearing in both scales, by measuring how much they are horizontally displaced from one another (representing the molar mass for that substance), and using the same distance from the concentration to be converted to determine the equivalent concentration in terms of the other unit. For example, on a certain monitor, the horizontal distance between the upper limits for parathyroid hormone in pmol/L and pg/mL may be 7 cm, with the mass concentration to the right. A molar concentration of, for example, 5 pmol/L would therefore correspond to a mass concentration located 7 cm to the right in the mass diagram, that is, approximately 45 pg/mL.
By units
Units do not necessarily imply anything about molarity or mass.
Note: Although 'mEq' for mass and 'mEq/L' are sometimes used in the United States and elsewhere, they are not part of SI and are now considered redundant.
If arterial/venous is not specified for an acid–base or blood gas value, then it generally refers to arterial, and not venous which otherwise is standard for other blood tests.[citation needed]
Acid–base and blood gases are among the few blood constituents that exhibit substantial difference between arterial and venous values.[13] Still, pH, bicarbonate and base excess show a high level of inter-method reliability between arterial and venous tests, so arterial and venous values are roughly equivalent for these.[51]
Autoantibodies are usually absent or very low, so instead of being given in standard reference ranges, the values usually denote where they are said to be present, or whether the test is a positive test. There may also be an equivocal interval, where it is uncertain whether there is a significantly increased level.
^The MCHC in g/dL and the mass fraction of hemoglobin in red blood cells in % are numerically identical in practice, assuming a RBC density of 1g/mL and negligible hemoglobin in plasma.
^Page 19 in: Stephen K. Bangert MA MB BChir MSc MBA FRCPath; William J. Marshall MA MSc MBBS FRCP FRCPath FRCPEdin FIBiol; Marshall, William Leonard (2008). Clinical biochemistry: metabolic and clinical aspects. Philadelphia: Churchill Livingstone/Elsevier. ISBN978-0-443-10186-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
^ abcdBrenden CK, Hollander JE, Guss D, et al. (May 2006). "Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study". American Heart Journal. 151 (5): 1006–11. doi:10.1016/j.ahj.2005.10.017. PMID16644322.
^ abcdefghijklSlon S (2006-09-22). "Serum Iron". University of Illinois Medical Center. Archived from the original on 2006-10-28. Retrieved 2006-07-06.
^ abcLuboldt, Hans-Joachim; Schindler, Joachim F.; Rübben, Herbert (2007). "Age-Specific Reference Ranges for Prostate-Specific Antigen as a Marker for Prostate Cancer". EAU-EBU Update Series. 5 (1): 38–48. doi:10.1016/j.eeus.2006.10.003. ISSN1871-2592.
^ abcdDerived from mass values using molar mass of 288.42g/mol
^ abcdefgDerived from molar values using molar mass of 288.42g/mol
^ abcdMedlinePlus > Testosterone Update Date: 3/18/2008. Updated by: Elizabeth H. Holt, MD, PhD, Yale University. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director
^ abcdDerived from mass values using molar mass of 330.46g/mol
^ abcdefValues taken from day 1 after LH surge in: Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P, Stricker R (2006). "Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer". Clinical Chemistry and Laboratory Medicine. 44 (7): 883–87. doi:10.1515/CCLM.2006.160. PMID16776638. S2CID524952.
^ abcdefgDerived from molar values using molar mass of 272.38g/mol
^ abcdTotal amount multiplied by 0.022 according to 2.2% presented in: Wu CH, Motohashi T, Abdel-Rahman HA, Flickinger GL, Mikhail G (August 1976). "Free and protein-bound plasma estradiol-17 beta during the menstrual cycle". J. Clin. Endocrinol. Metab. 43 (2): 436–45. doi:10.1210/jcem-43-2-436. PMID950372.
^ abDerived from mass values using molar mass of 314.46 g/mol
^ abcdDerived from molar values using molar mass of 362 g/mol
^ abcdefghFriedrich N, Alte D, Völzke H, et al. (June 2008). "Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: results of the Study of Health in Pomerania (SHIP)". Growth Hormone & IGF Research. 18 (3): 228–37. doi:10.1016/j.ghir.2007.09.005. PMID17997337.
^ abcdReusch J, Ackermann H, Badenhoop K (May 2009). "Cyclic changes of vitamin D and PTH are primarily regulated by solar radiation: 5-year analysis of a German (50 degrees N) population". Horm. Metab. Res. 41 (5): 402–07. doi:10.1055/s-0028-1128131. PMID19241329. S2CID260166796.
Washington, Department of Laboratory Medicine. Retrieved Mars 2011
^ abConverted from mass values using molar mass of 360.44 g/mol
^ abcdTiu SC, Choi CH, Shek CC, et al. (January 2005). "The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling". The Journal of Clinical Endocrinology and Metabolism. 90 (1): 72–78. CiteSeerX10.1.1.117.5182. doi:10.1210/jc.2004-1149. PMID15483077.
^Derived from mass values using molar mass of 46g/mol
^ abcdeDerived from mass values using 64,500 g/mol. This molar mass was taken from: Van Beekvelt MC, Colier WN, Wevers RA, Van Engelen BG (2001). "Performance of near-infrared spectroscopy in measuring local O2 consumption and blood flow in skeletal muscle". J Appl Physiol. 90 (2): 511–19. doi:10.1152/jappl.2001.90.2.511. PMID11160049. S2CID15468862.
^ abcdDerived from mass concentration, using molar mass of 64,458 g/mol. This molar mass was taken from: Van Beekvelt MC, Colier WN, Wevers RA, Van Engelen BG (2001). "Performance of near-infrared spectroscopy in measuring local O2 consumption and blood flow in skeletal muscle". J Appl Physiol. 90 (2): 511–19. doi:10.1152/jappl.2001.90.2.511. PMID11160049. S2CID15468862.. Subsequently, 1 g/dL = 0.1551 mmol/L
^ abDemirin H, Ozhan H, Ucgun T, Celer A, Bulur S, Cil H, Gunes C, Yildirim HA (2011). "Normal range of mean platelet volume in healthy subjects: Insight from a large epidemiologic study". Thromb. Res. 128 (4): 358–60. doi:10.1016/j.thromres.2011.05.007. PMID21620440.
^ abLozano M, Narváez J, Faúndez A, Mazzara R, Cid J, Jou JM, Marín JL, Ordinas A (1998). "[Platelet count and mean platelet volume in the Spanish population]". Med Clin (Barc) (in Spanish). 110 (20): 774–77. PMID9666418.
Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., "Coagulation." In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327–58.
^ ab"Home". pathology.bsuh.nhs.uk. Retrieved November 20, 2009.
^ abcdDerived from mass using molar mass of 25,106 g/mol
^ abSipahi T, Kara C, Tavil B, Inci A, Oksal A (March 2003). "Alpha-1 antitrypsin deficiency: an overlooked cause of late hemorrhagic disease of the newborn". Journal of Pediatric Hematology/Oncology. 25 (3): 274–75. doi:10.1097/00043426-200303000-00019. PMID12621252.
^ abDerived from mass values using molar mass of 44324.5 g/mol
^ abDerived from molar values using molar mass of 44324.5 g/mol
^Ageno W, Finazzi S, Steidl L, et al. (2002). "Plasma measurement of D-dimer levels for the early diagnosis of ischemic stroke subtypes". Archives of Internal Medicine. 162 (22): 2589–93. doi:10.1001/archinte.162.22.2589. hdl:2434/51239. PMID12456231.
^ abcdPage 700 in: Richard C. Dart (2004). Medical Toxicology. Lippincott Williams & Wilkins=year=2004. ISBN9780781728454.
^The UK Electronic Medical Compendium recommends 0.4–0.8 mmol/L plasma lithium level in adults for prophylaxis of recurrent affective bipolar manic-depressive illness Camcolit 250 mg Lithium CarbonateArchived 2016-03-04 at the Wayback Machine Revision 2 December 2010, Retrieved 5 May 2011
^ abAmdisen A. (1978). "Clinical and serum level monitoring in lithium therapy and lithium intoxication". J. Anal. Toxicol. 2 (5): 193–202. doi:10.1093/jat/2.5.193.
^ abR. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 851–54.
^One study (Solomon, D.; Ristow, W.; Keller, M.; Kane, J.; Gelenberg, A.; Rosenbaum, J.; Warshaw, M. (1996). "Serum lithium levels and psychosocial function in patients with bipolar I disorder". The American Journal of Psychiatry. 153 (10): 1301–07. doi:10.1176/ajp.153.10.1301. PMID8831438.) concluded a "low" dose of 0.4–0.6 mmol/L serum lithium treatment for patients with bipolar 1 disorder had less side effects, but a higher rate of relapse, than a "standard" dose of 0.8–1.0 mmol/L. However, a reanalysis of the same experimental data (Perlis, R.; Sachs, G.; Lafer, B.; Otto, M.; Faraone, S.; Kane, J.; Rosenbaum, J. (2002). "Effect of abrupt change from standard to low serum levels of lithium: A reanalysis of double-blind lithium maintenance data". The American Journal of Psychiatry. 159 (7): 1155–59. doi:10.1176/appi.ajp.159.7.1155. PMID12091193. S2CID12103424.) concluded the higher rate of relapse for the "low" dose was due to abrupt changes in the lithium serum levels[improper synthesis?]
^ abJohn Marx; Ron Walls; Robert Hockberger (2013). Rosen's Emergency Medicine – Concepts and Clinical Practice. Elsevier Health Sciences. ISBN9781455749874.