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Year : 2014  |  Volume : 1  |  Issue : 1  |  Page : 10-14

Clinical laboratory tests: Right choice of the test for the benefit of the patient

1 Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, International Medical University, Kuala Lumpur, Malaysia
2 Department of Biochemistry, Faculty of Medicine, Benghazi University, Benghazi, Libya

Date of Web Publication21-Oct-2014

Correspondence Address:
Dhastagir Sultan Sheriff
Faculty of Medicine, Benghazi University, Benghazi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2394-2010.143319

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Clinical laboratory tests form one of the major components of evidence-based medicine. Results obtained for the cases referred carry variations due to biological parameters including the effect of age, pre-analytical errors, analytical errors, as well as interpretation of the results obtained. In the present study, some of these concerns have been addressed with a view to prepare the physician to understand, interpret, as well as choose the required tests for a specific case in question.

Keywords: Analytical variation, biological variation, clinical laboratory tests, elderly patients, pre-analytical variation

How to cite this article:
Sheriff SO, Sheriff DS. Clinical laboratory tests: Right choice of the test for the benefit of the patient. J Health Res Rev 2014;1:10-4

How to cite this URL:
Sheriff SO, Sheriff DS. Clinical laboratory tests: Right choice of the test for the benefit of the patient. J Health Res Rev [serial online] 2014 [cited 2022 Sep 26];1:10-4. Available from: https://www.jhrr.org/text.asp?2014/1/1/10/143319

  Introduction Top

Clinical laboratory tests form one of the major components of evidence-based medicine. Results obtained for the cases referred carry variations due to biological parameters including the effect of age, pre-analytical errors, analytical errors, as well as interpretation of the results obtained.

While test-related variables may be factors, intra-individual biological variation is much more common and may be the explanation for discrepant results. For this reason, physicians need to know which laboratory tests are associated with significant intra-individual biological variation as well as the magnitude of possible changes.

When serial tests are performed on a patient, there are many possible reasons for unanticipated discrepant results. [1],[2],[3] Some are associated with preparations for and conditions of testing (pre-analytical variation), some with the test procedures themselves (analytical variation), and some with biological variations in the individual patient. Therefore, physicians need to be aware of the factors associated with biological or age-related variations in test results before requesting for further investigations.

  Pre-Analytical Variation Top

Pre-analytical factors that may influence the test results include patient preparation and positioning, type of sample (venous or capillary), type of collection tube used, and specimen transport and storage. [1],[2],[4] Leaving a phlebotomy tourniquet in place for a few minutes longer than usual during blood sampling may cause standard tests to vary significantly. For example, when tourniquet use is prolonged, cholesterol levels increase by 1.5% after 2 min of wear and by 10-15% after 5 min. [1],[5]

Simple factors such as position of the patient (sitting vs. lying), movement, or exercise can also cause the laboratory values of some analytes to differ significantly. [1],[2] For example, vigorous exercise shortly before blood collection has been associated with up to a 6% increase in total cholesterol level. A change in position between sitting and lying can produce a 15% variation in total cholesterol and high-density lipoprotein (HDL) cholesterol determinations. [1],[5] As a result of these interactions, the National Cholesterol Education Program has recommended that lipid profiles be drawn in a consistent fashion after the patient has been either lying or sitting quietly for at least 5 min. [1],[2]

For some types of analyses, there can also be marked differences between venous and capillary finger-stick determinations. Studies comparing hematologic parameters in venous and capillary blood samples obtained from healthy adults have shown up to a 32% decrease in platelet count, up to a 10% increase in hemoglobin level, and up to a 23% increase in total leukocyte count for the capillary specimens. [4],[5]

  Analytical variation Top

As modern fully automated analyzers have replaced manual test procedures, analytical variation has become a relatively minor cause of test variation compared with biological variation. Generally, it is expected to contribute half or less than half as much to total test variation as does biological variation. [1],[2]

  Biological variation Top

Biological variation may refer to an individual patient's results over a period of time relative to a group mean (inter-individual variation) or relative to the patient's own mean (intra-individual variation). In some circumstances, inter-individual biological variation may be explained and partitioned according to recognized demographic factors, such as age, sex, race, pregnancy, or history of smoking. [1],[2] Intra-individual variation tends to be smaller than inter-individual variation.

Analytes that display considerable intra-individual biological variation are listed in [Table 1]. The typical biological variation is given as a percentage of the value of the analyte in question, as well as the critical difference that would represent a true difference between serial determinations in 95% of instances (95% confidence interval). [6],[7],[8],[9] This table also provides the reference ranges used in our laboratory. The terms "reference range" and "reference interval" refer to the 95% distribution (mean plus two standard deviations) of test results in the reference population and are preferred to the term "normal range." When the percent of critical difference is multiplied by the upper limit of the reference range, the absolute value that would constitute a critical difference between serial determinations is obtained. [10] The values given in [Table 1] are for the reference ranges adopted in our laboratory, but a similar table can be easily constructed for the reference ranges of any other laboratory or institution. Intra-individual variation can occur within the same day or from one day to another. For instance, serum bilirubin concentrations show a pronounced downward trend in the afternoon; the mean value after 6 p.m. is 30% lower than the mean value in the morning. [11] Triglyceride, phosphate, urea, and creatinine levels are lowest in the morning and highest in the early evening. Hemoglobin, hematocrit, and red blood cell count fluctuations usually repeat on a regular diurnal basis, the morning values typically being the highest. Mean leukocyte counts are usually highest in the afternoon. Surveys of physicians' attitudes regarding the clinical significance of changes in serial test results in individual patients have repeatedly shown that most physicians require a substantial change before they alter diagnosis or treatment. [1],[2],[3] For example, the individual variation in total leukocyte count was shown to as much as 3.0 × 10 3 /μl within a single day and as much as 5.0 × 10 3 /μl over a 3-day period. As would be expected, inter-individual variations were even greater. Similarly, the hemoglobin values showed an intra-individual shift of as much as 1.5 g/dl during the course of a single day and as much as 2.0 g/dl over 3 days. [7]
Table 1: Analytes with considerable intra-individual biological variation

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In other studies, a proportionately similar magnitude of change has been noted for platelet counts; intra-individual shifts were at least 75 × 10 3 /μl in a single day and up to 125 × 10 3 /μl over several days. Among the different cell types that compose the leukocyte differential, the greatest changes are usually seen in the absolute neutrophil, monocyte, and eosinophil counts. Only the basophil and lymphocyte populations tend to remain relatively constant. [8],[10]

  Laboratory date in the elderly Top

Reference ranges of laboratory tests for the elderly may differ from those for the general population, the differences representing the normal aging processes. Adequate reference ranges for laboratory testing in the elderly are generally lacking, as is specific information on persons over age 75, who, ironically, constitute the fastest-growing segment of the geriatric population. [3],[12],[13] Ideally, the geriatric population would be well defined in terms of race, sex, age, and health status. However, many confounding factors may be present in the elderly, such as known comorbid illness, occult disease, malnutrition, drug therapy, and environmental factors. [14]

The fact that a variety of parameters change with age may be attributed to the effect of aging on various organ systems. Although there is considerable variation from one person to the other, the physiologic decline in cardiac, renal, pulmonary, and other organ systems generally begins between the third and fourth decades of life and subsequently follows a linear progression into old age. [2],[3],[13] What is surprising is the extent to which some laboratory values change with age while other values do not [Table 2]. Although anemia is common in the elderly, it is most often associated with a variety of chronic diseases. Most investigators have dismissed the notion of senile anemia. Thus, any degree of anemia in the elderly that is outside of the usual reference ranges must be explainable on a clinical basis. The World Health Organization has defined an abnormal haemoglobin value as less than 13 g/dl in men and less than 12 g/dl in women. However, some authorities accept reference values as low as 11 g/dl in elderly women and as low as 11.5 g/dl in elderly men as not meriting an extensive workup. [2],[3] The leukocyte count appears to be slightly lower in the elderly than in the general population, a difference usually attributed to a slight decrease in the total lymphocyte count. [12] Serum vitamin B 12 levels may decrease slightly with age. The low end of the normal range is considered to be 150 pg/ml in older adults as opposed to 190 pg/ml in younger adults. [13]
Table 2: Laboratory values that do and do not change with age (over 65 years unless otherwise specified)

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Erythrocyte sedimentation rate (ESR) increases with age, and the annual rate of increase has been quantified at 0.22 mm/h. For the elderly, the reference range for the ESR includes values up to 40 mm/h in men and 45 mm/h in women. [14],[15] Thus, the clinical finding of an elevated ESR in an elderly patient can be problematic, since it may or may not reflect the presence of underlying disease. In general, an ESR less than or equal to 40 to 45 mm/h has little importance, unless an abnormal clinical correlation can be made. By comparison, an ESR greater than 100 mm/h is almost always associated with serious underlying systemic disease. [16]

  Biochemical tests Top

An elevated alkaline phosphatase level may be present in more than 10% of the elderly, most often in women. [2],[3] The 20-37% increase that occurs between the ages of 30 and 80 years has been attributed to extrahepatic sources, such as malabsorption, bone disorders or renal insufficiency. An absolute value of 140 U/l has been suggested by some authorities as an upper limit of the reference range for elderly patients. [13]

Total cholesterol level increases by 30-40 mg/dl by age 55 in women and age 60 in men. In men, HDL cholesterol level increases 30% between ages 30 and 80, whereas in women it decreases by 30% during the same period. [2],[13] Triglyceride level increases by 30% in men and 50% in women between ages 30 and 80. [2],[3]

Though the slight decline in serum albumin noted with age is generally not felt to be of clinical significance, one of its consequences is that the reference range for substances bound to albumin may be altered, even though the unbound fraction remains constant. For instance, while the total serum calcium level falls slightly with age, the ionized, or free, serum calcium level remains unchanged. [12]

Laboratory values of serum creatinine do not change with age. However, they still have important clinical significance because despite significant decreases in creatinine clearance with increasing age, serum creatinine does not necessarily increase, since muscle mass from which creatinine is derived also declines with aging. [2],[3] Thus, in the elderly, a normal serum creatinine value does not necessarily mean that renal function is normal; the creatinine clearance is much more important than the absolute serum creatinine value. Such potential changes in creatinine clearance must be considered when treating the elderly because of the possibility of drug toxicity when standard dosing is prescribed for therapeutic agents that are excreted by the kidney, such as digoxin (Lanoxin) or aminoglycosides. Fortunately, a relatively accurate estimate of creatinine clearance can be made on the basis of the patient's age, serum creatinine value, and weight. Individual formulas are provided in [Table 3]. [3],[13]
Table 3: Formulas for calculating various laboratory values in the elderly

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  Pulmonary tests Top

With regard to pulmonary function, PaO 2 decreases by 25% between the third and eighth decades of life, reflecting decreased lung elasticity as well as decreased alveolar surface area. For interpretation of blood gas results, the PaO 2 of a 75-year-old generally should be 75 mm Hg or higher. A formula for calculating the PaO 2 in relation to age is provided in [Table 3]. [2],[3]

  Endocrine tests Top

Both triiodothyronine (T 3 ) and thyrotropin (TSH) values may decrease slightly with age, while the thyroxine (T 4 ) level tends to remain constant. A small increase in fasting blood glucose level occurs with age, amounting to about 2 mg/dl for each decade of life after the age of 30. [12] However, the 1 h postprandial blood glucose level increases by 10 mg/dl per decade of life after the age of 30. The 2 h postprandial blood glucose level, as a general rule of thumb, should not exceed 140 mg/dl for patients under the age of 40 and should not exceed 100 mg/dl plus the patient's age in years for patients over the age of 40. [2],[3],[13]

  Conclusion Top

Therefore, when confronted with unexpected differing test results from repeated testing in the same individual, physicians should be aware of explanations other than laboratory error and change in the patient's clinical status. Intra-individual biological changes and age-associated physiological changes influence the laboratory results, and therefore, a physician must be educated of such influences by laboratory consultants. [17]

There has to be a good communication between the physician and clinical laboratory services. Such a relationship will be mutually beneficial for the physician as well as the laboratory personnel to provide the best services to the needy patient.

  References Top

1.Rock RC. Interpreting laboratory tests: A basic approach. Geriatrics 1984;39:49-50, 53-4.  Back to cited text no. 1
2.Cavalieri TA, Chopra A, Bryman PN. When outside the norm is normal: Interpreting lab data in the aged. Geriatrics 1992;47:66-70.  Back to cited text no. 2
3.Kelso T. Laboratory values in the elderly: Are they different? Emerg Med Clin North Am 1990;8:241-54.  Back to cited text no. 3
4.Daae LN, Halvorsen S, Mathisen PM, Mironska K. A comparison between haematological parameters in 'capillary' and venous blood from healthy adults. Scand J Clin Lab Invest 1988;48:723-6.  Back to cited text no. 4
5.Greenland P, Bowley NL, Meiklejohn B, Doane KL, Sparks CE. Blood cholesterol concentration: Fingerstick plasma vs venous serum sampling. Clin Chem 1990;36:628-30.  Back to cited text no. 5
6.Costongs GM, Janson PC, Bas BM, Hermans J, van Wersch JW, Brombacher PJ. Short-term and long-term intra-individual variations and critical differences of clinical chemical laboratory parameters. J Clin Chem Clin Biochem 1985;23:7-16.  Back to cited text no. 6
7.Statland BE, Winkel P, Harris SC, Burdsall MJ, Saunders AM. Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers. Am J Clin Pathol 1978;69:48-54.  Back to cited text no. 7
8.Costongs GM, Janson PC, Bas BM, Hermans J, van Wersch JW, Brombacher PJ. Short-term and long-term intra-individual variations and critical differences of haematological laboratory parameters. J Clin Chem Clin Biochem 1985;23:69-76.  Back to cited text no. 8
9.Lassen JF, Brandslund I, Antonsen S. International normalized ratio for prothrombin times in patients taking oral anticoagulants: Critical difference and probability of significant change in consecutive measurements. Clin Chem 1995;41:444-7.  Back to cited text no. 9
10.Franzini C. Relevance of analytical and biological variations to quality and interpretation of test results: Examples of application to haematology. Ann Ist Super Sanita 1995;31:9-13.  Back to cited text no. 10
11.Pocock SJ, Ashby D, Shaper AG, Walker M, Broughton PM. Diurnal variations in serum biochemical and haematological measurements. J Clin Pathol 1989;42:172-9.  Back to cited text no. 11
12.Tietz NW, Shuey DF, Wekstein DR. Laboratory values in fit aging individuals-sexagenarians through centenarians. Clin Chem 1992;38:1167-85.  Back to cited text no. 12
13.Hurwitz J. Interpreting laboratory tests in the elderly. Clin Biochem 1993;26:433-4.  Back to cited text no. 13
14.McPherson K, Healy MJ, Flynn FV, Piper KA, Garcia-Webb P. The effect of age, sex and other factors on blood chemistry in health. Clin Chim Acta 1978;84:373-97.  Back to cited text no. 14
15.Sharland DE. Erythrocyte sedimentation rate: The normal range in the elderly. J Am Geriatr Soc 1980;28:346-8.  Back to cited text no. 15
16.Brigden M. The erythrocyte sedimentation rate. Still a helpful test when used judiciously. Postgrad Med 1998;103:257-62, 272-4.  Back to cited text no. 16
17.Burtis CA, Ashwood E, Bruns D. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. St. Louis MO, USA: Saunders, Elsevier Health Sciences Publications; 2012.  Back to cited text no. 17


  [Table 1], [Table 2], [Table 3]


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Analytical variation
Biological variation
Laboratory date ...
Biochemical tests
Pulmonary tests
Endocrine tests
Pre-Analytical V...
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