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When to collect blood specimens: midmorning vs fasting samples.

Laboratory data are routinely expressed numerically without comments on their uncertainty. Furthermore, the specimens may have been collected any time during the working day for convenience and to equalize the need for personnel during working hours. However, insufficient data exist on the optimal quality:cost ratio of such elective routine specimen collection. Our study was designed to determine the magnitude of changes induced by deviating from the recommended and standardized procedures of collecting fasting specimens early in the morning. The purpose of this study was to provide a rational basis for deciding the regimen for routine specimen collection.

Materials and Methods

ANALYTES

The analytes studied were the 32 most common blood tests (excluding HbA1c) according to the laboratory statistics of the Helsinki City Hospitals, which perform ~3 000 000 laboratory studies yearly. These 32 analytes account for >50% of the total amount.

The analytes were as follows: the blood picture (leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, and platelet counts) and leukocyte differential count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils); erythrocyte sedimentation rate; thromboplastin time; the serum concentrations of total calcium, potassium, sodium, creatinine, glucose, total cholesterol, triglycerides, thyrotropin (S-TSH) [3] free thyroxine (S-[T.sub.4]F), and C-reactive protein; and the serum activities of aspartate aminotransferase, alkaine aminotransferase, alkaline phosphatase, [Gamma]-glutamyltransferase, total creatine kinase (S-CK), and subunit B of creatine kinase (S-CK-B). Inorganic phosphate was measured only on inpatients.

SUBJECTS

The study was performed on consenting subjects. The protocol of the study was approved by the ethics committee of Helsinki City Hospital, and we obtained written informed consent from every subject. The subjects formed two groups: group 1 (ambulatory subjects corresponding to outpatients) consisting of subjectively healthy individuals with no medication other than oral contraceptives for 1 week before the experiment (n = 51; 31 women, ages 18-60 years; mean, 36.7 years; 20 men, ages 23-63 years; mean, 42.4 years). Group 2 (inpatients) consisted of inpatients in different wards in Maria Hospital, Helsinki (n = 51; 13 women, ages 65-87; mean, 75.2 years; 38 men, ages 32-80; mean, 58.6 years.). The nature of the inpatients' illnesses was not recorded because the study was performed explicitly on a general inpatient population to assess practical guidelines for specimen collection in general hospitals. However, there were equal numbers of patients from surgical and medical wards. No pediatric or gynecological patients were included. All inpatients had to be conscious and oriented to obtain informed consent.

STUDY PROTOCOL AND SPECIMEN COLLECTION

The study protocol consisted of three collections of specimens and a meal, all during the same day:

(a) 0800, first specimen from fasting subjects (specimen 1);

(b) breakfast;

(c) 0930, second specimen (40-80 min after breakfast; specimen 2);

(d) sitting or walking around indoors, no eating, smoking, intake of liquid, or exercise; the inpatients were mostly supine; and

(e) 1100, third specimen (specimen 3).

All specimens from ambulatory subjects were collected by an experienced laboratory technician, according to the Scandinavian recommendations (1), i.e., the subject sat for at least 15 min before venipuncture with no tourniquet, whereas inpatients were mostly supine. Blood was collected from a cubital vein with Venoject needles (20 G) in vacuum serum and EDTA tubes (Terumo Co.). No serum-separator tubes were used. The outpatients were instructed to have a breakfast similar to that of a routine working day from a selection of foodstuffs commonly used in Finland (corresponded roughly to a continental breakfast). The energy intake was <500 kJ for 11 participants, 500-1000 kJ for 20 participants, and >1000 kJ for 20 participants. The inpatients were given a routine hospital breakfast (1500 kJ).

ANALYSIS

The thromboplastin time and erythrocyte sedimentation rate were analyzed immediately after specimen collection (thromboplastin time with ACL1000, Instrumentation Laboratory Spa; and erythrocyte sedimentation rate with the vacuum tube method, Terumo). The complete blood count and differential count were analyzed within 3 h with a Coulter Max M analyzer (Coulter Corp.). For serum samples, the tubes were left to stand at room temperature for 30 min and then centrifuged at 16008 for 10 min. The serum was separated and frozen (-20[degrees]C) for 2-5 days and then analyzed with a Hitachi 704 (Hitachi Ltd.) analyzer using routine procedures in the clinical chemistry laboratory of Maria Hospital. Cholesterol and triglycerides were analyzed with Kone Progress Plus (Kone Instruments Oy). All the samples of one patient were analyzed in the same series, and routine quality-control procedures were carried out. S-TSH and S-[T.sub.4]F were analyzed in the laboratory of Laakso Hospital, Helsinki, 5-T4F with an Axsym analyzer (Abbott Laboratories) and S-[T.sub.4]H with Delfia (Wallac Oy).

DATA PROCESSING AND STATISTICS

The data obtained were analyzed by ANOVA for repeated measurements and by the Scheffe test for calculating statistically significant changes. The multicomparison significance level was at 99%. The analytical CV ([CV.sub.anal]) was calculated with the same analyzers as the patient samples by analyzing a sample in the middle of the health-related reference interval 20 times in the same analytical run. The total CV ([CV.sub.total]) was calculated as the average of the individual within-person CVs from the three measurements performed per subject. The clinical significance of the observed changes was estimated by comparing them to previously published data (2-4). For the experimentally derived critical difference, the "ultra-short-term biological variation' of Costongs and co-workers (2, 3) and the 95% level for individual changes were chosen for comparison. The homogeneity of data was estimated by calculating the index of heterogeneity (i) according to Harris and Fraser (5, 6).

Results

The results show statistically significant changes occurring in 22 of the 32 analytes studied. The within-person CVs were systematically greater (up to 14-fold) than the analytical CVs (Tables 1 and 2).

The results of C-reactive protein for the outpatients (group 1) are not shown because the values were below the detection limit (10 mg/L) in all subjects. The leukocyte count was higher in inpatients, and both populations showed a similar, constant rise during the study. The differential count revealed a similar behavior in both groups, with increasing neutrophil and decreasing lymphocyte and monocyte counts. The hemoglobin and hematocrit values were stable in inpatients but increased in outpatients. The total calcium concentration rose in outpatients and was stable in inpatients. Sodium, creatinine, aspartate aminotransferase, alanine aminotransferase, [gamma]-glutamyltransferase, cholesterol, and S-[T.sub.4]F all revealed a change in the opposite direction in the two test groups, with the outpatient group showing more statistically significant changes. Similar changes of means in both groups were observed in 5-CK, glucose, triglyceride, and 5-TSH concentrations.

In >50% of the analytes, some individual changes exceeded the level of clinical significance (Table 3). It should be noted that diabetics were also included in the inpatient population, which explains the higher mean fasting glucose concentration.

Discussion

Quality control and quality assurance are necessary and inextricable parts of laboratory work. To ensure the quality of laboratory results, all factors having an effect on the results should be minimized. Traditionally, this is (or should be) done by quality control and perhaps by issuing standing rules concerning specimen collection. The collection should, for example, be done after 15 min of sitting (1), without a tourniquet, and preferably in the morning and fasting. The timing of specimen collection and the physiological state of the patient during the specimen collection session are unfortunately often neglected, and many of the recommendations are based on an "educated guess". Furthermore, in a cost-effective laboratory, the collection of specimens should be allocated to working hours as evenly as possible. Circadian intraindividual variations are known for a number of analytes (e.g., iron and 5-TSH); however, most of the analytes studied here are considered to be stable enough to be measured any time of day. Circadian rhythms are reported to be related to several aspects of daily life (7) but, according to some authors (6), are of no interest for most of the common analytes. Unfortunately, it is very unlikely that the patients are still fasting if the specimens are collected late in the morning or during the lunch break.

Our data now establish the consequences of deviating from the traditional morning fasting-state sample collection procedure. Especially worth noting is that the magnitude of the within-person CV caused by delaying specimen collection for 3 h may be up to 14-fold compared with the analytical CV. Although the absolute changes are relatively small, the focus of quality-control procedures should be reconsidered.

Clinical and statistical significance are different concepts and should not be mixed. However, the existence of statistically significant changes of the means in this study prompts one to take a stand in regard to the matters of timing and fasting status when issuing standing rules concerning specimen collection. In addition, the desired level of precision must be defined separately for different clinical situations. The concept of laboratory imprecision also must include patient-derived factors to be clinically useful. Clinical usefulness relates to clinical decision limits. There are several approaches to these decision limits, on the basis of interviews with clinicians (4) and different calculations (2, 3, 8, 9). The validity of these approaches has been discussed (10-12). However, the main question remains: who should decide what is considered a significant clinical change? From a practical point of view, the opinions of clinicians should be more pragmatic; however, they often are stricter (4) than those based on statistics of the within-person or total biological variation. Clinicians are to judge what kind of change in the value of a laboratory test is medically important. However, they are usually unaware of the magnitude of biological variation. On the other hand, the biologically derived critical difference is calculated for 95% of the population. Therefore, when multiple univariate measurements are analyzed, there is an increased risk of getting a significantly deviating result [for 1 measurement the risk is 5%,for n measurements the risk is 100 X (1 - 0.95n)%]. However, this approach has been useful for adaptive forecasting based on models that describe time-related biological processes such as tumor growth (13). It should also be noted that most of the published biological variations are based on the variability in healthy persons and therefore may not be valid in sick subjects.

In the present study, most of the changes observed were below the biological (experimental) and medically derived clinical decision limits; however, individual results exceeded them in >50% of the analytes investigated. The percentages of individuals exceeding the critical differences (Table 3), however, were not more than the 5% expected from the data of Costongs and co-workers (2, 3). In the majority of cases, the experimentally derived critical differences were broader than the clinically derived critical differences of Skendzel et al. (4).

All volunteers (outpatients) considered themselves healthy and had C-reactive protein values <10 mg/L. One of the volunteers had an 5-CK value of 11 500 U/L (upper reference limit, 270 U/L), which was the only result excluded from the data processing. The reason for the high enzyme activity was found to be strenuous physical exercise on the day before specimen collection, and the 5-CK had returned to the health-related reference interval 2 weeks later. The age of the inpatient population was higher than in the ambulant (outpatient) population. However, according to Fraser and co-workers (8, 9), the estimates of within-subject biological variation are similar in old and young subjects, indicating that this aspect of homeostasis is not compromised in the elderly. Therefore, the smaller change in hematological indicators of inpatients most likely reflects the lack of physical exercise and upright posture in comparison with outpatients. This difference underlines the sensitivity of the changes, because the outpatients were instructed to sit or walk indoors and to avoid physical stress during the test session. However, the concentrations of the blood components showed no clear differences between the two groups. In the outpatient group, we found one undiagnosed case of hypercholesterolemia and one case of subclinical hypothyroidism. These results were included in the calculations because such patients are also encountered in the laboratory routine. These deviating results did not have an effect on the statistical significance of the differences; however, the index of heterogeneity was affected. Therefore, the indexes calculated without these "outliers" are shown in the tables.

The preanalytical phase has a greater effect on the outcome of laboratory results than the analysis itself. We feel that quality control for a laboratory should include preanalytical factors more than is the current practice. International standards such as I5025 do not comment on the pathophysiological state or preparation of the patient before obtaining (blood) specimens in sufficient detail. The clinician should know that a change in the laboratory results does not necessarily imply a change in the health status of the patient. Different medical specialities and different clinical situations may require different standards and procedures. Thus, the appropriate level of precision for laboratory tests should be better defined for different situations in patient care. Clinical decision making should be based on facts more than experience and educated guesses.

This research was supported by the Signe and Ane Gyllenberg, the Ella and Georg Ehrnrooth, the Magnus Ehrnrooth, the Oskar Oflund, and the Yrjo Jahnsson Foundations (B.D.). We thank the volunteers and the personnel of Maria Hospital. We also thank Brigitta Kuronen for supervising the assays and Ralph Grasbeck, head of the Biochemistry group at the Minerva Institute, for critical assistance in preparing the manuscript.

References

(1.) Alstrom T, Grasbeck R, Lindblad B, Solberg H, Winkel P, Viinikka L. Establishing reference values from adults: recommendation on procedures for the preparation of individuals, collection of blood, and handling and storage of specimens. Stand J Clin Lab Investig 1993; 53:649-52.

(2.) Costongs G, Janson P, Bas B. Short-term and long-term intraindividual variations and critical differences of clinical chemistry laboratory parameters. J Clin Chem Clin Biochem 1985;23:7-16.

(3.) Costongs G, Janson P, Bas B, Hermans J, Brombacher P, Van Wersch J. Short-term and long-term intra-individual variations and critical differences of haematology laboratory parameters. J Clin Chem Clin Biochem 1985;23:69-76.

(4.) Skendzel L, Barnett R, Platt R. Medically useful criteria for analytic performance of laboratory tests. Am J Clin Pathol 1985;83:200-5.

(5.) Harris E. Statistical aspects of reference values in clinical pathology. Prog Clin Pathol 1981;8:45-66.

(6.) Fraser C, Harris E. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27: 409-37.

(7.) Solberg HE, Grasbeck R. Reference values. Adv Clin Chem 1989; 27:1-79.

(8.) Fraser CG, Wilkison S, Neville R, Knox J, King J, MacWalter R. Biological variation of common hematologic laboratory quantities in the elderly. Am J Clin Pathol 1989;92:465-70.

(9.) Fraser CG, Cummings S, Wilkison S, Neville RG, Knox JD, Ho 0, MacWalter RS. Biological variability of 26 clinical chemistry analytes in elderly people. Clin Chem 1989;35:783-6.

(10.) Werner M. Linking analytic performance goals to medical outcome. Clin Chim Acta 1997;260:99-115.

(11.) Doumas B. The evolution and limitations of accuracy and precision standards. Clin Chim Acta 1997;260:145-62.

(12.) Fraser C, Petersen P, Ricos C, Haeckel R. Proposed quality specifications for the imprecision and inaccuracy of analytical systems for clinical chemistry. Eur J Clin Chem Clin Biochem 1992;30:311-7.

(13.) Winkel P. Application of time series analysis in the clinical setting. Stand J Clin Lab Investig 1995;55(Suppl 222):11-6.

ESA LEPPANEN [1], [2] and BENOTT DUGUE [2] *

[1] Helsinki City Health Department, Maria Hospital, 00180 Helsinki, Finland, and [2] Minerva Foundation Institute for Medical Research, Tukholmankatu 2, FIN-00250 Helsinki, Finland.

[3] Nonstandard abbreviations: S-TSH, serum thyrotropin; S-T4F, serum free thyroxine; and S-CK, serum creatine kinase.

* Author for correspondence. Fax 358-9-4771025.

Received July 6, 1998; revision accepted September 10, 1998.
Table 1. Hematological analytes from samples obtained from the same
subjects (a) during the morning. (b)

Analytes Mean, S1 (c)

Leukocytes, IN (d) 8.0
 [10.sup.9]/L OUT (d,e) 5.5
Neutrophils, % IN (d,e) 65.3
 OUT (d,e) 50.0
Lymphocytes, % IN (d,e) 21.1
 OUT (d,e) 35.6
Monocytes, % IN (e) 10.1
 OUT (d,e) 9.6
Eosinophils, % IN (d,e) 3.2
 OUT (d,e) 4.4
Basophils, % IN 0.3
 OUT 0.3
Erythrocytes, IN 4.28
 [10.sup.12]/L OUT (e) 4.50
Hemoglobin, g/L IN 131
 OUT (e) 136
Hematocrit, vol. IN 0.383
 fraction OUT (e) 0.399
MCV, fL IN 89.5
 OUT 89.0
MCH, pg IN 30.6
 OUT 30.4
MCHC, g/L IN 341
 OUT 341
Platelets, IN 264
 [10.sup.9]/L OUT (d) 257
Sedimentation IN 35
 rate, mm/h OUT 7
TT, % IN 89
 OUT 111

 Distribution of changes, mean (extreme values)

Analytes [[DELTA].sub.(2-1)] [[DELTA].sub.(3-1)]

Leukocytes, 0.2 (-1.3; 2.3) 0.4 (-1.7; 2.5)
 [10.sup.9]/L 0.6 (-0.8; 3.5) 0.7 (-1.1; 3.0)
Neutrophils, % 3.2 (-3.3; 10.3) 3.2 (-6.9; 18.6)
 6.2 (-3.2; 17.5) 5.1 (-6.3; 18.5)
Lymphocytes, % -2.0 (-11.4; 4.3) -2.4 (-14.7; 3.9)
 -4.1 (-17.6; 4.3) -3.2 (-14.1; 6.9)
Monocytes, % -0.7 (-4.7; 2.7) -0.3 (-4.0; 2.7)
 -0.9 (-2.7; 18.7) -0.7 (-3.1; 1.4)
Eosinophils, % -0.4 (-2.7; 0.6) -0.6 (-2.8; 0.6)
 -1.0 (-3.9; 0.1) -1.2 (-4.3; 0.3)
Basophils, % 0.0 (-1.9; 0.8) 0.0 (-2.2; 2.6)
 -0.1 (-1.4; 0.8) 0.0 (-1.3; 5.8)
Erythrocytes, -0.01 (-0.29; 0.45) -0.02 (-0.55; 0.48)
 [10.sup.12]/L 0.1 (-0.3; 0.3) -0.1 (-0.3; 0.2)
Hemoglobin, g/L 0 (-8; 12) -1.0 (-15; 13)
 1.8 (-9; 10) 0.9 (-3; 11)
Hematocrit, vol. 0.00 (-0.03; 0.04) 0.00 (-0.04; 0.04)
 fraction 0.01 (-0.03; 0.03) 0.00 (-0.01; 0.02)
MCV, fL 0.1 (-2.3; 2.4) 0.2 (-2.3; 2.4)
 0.2 (-1.4; 1.5) 0.1 (-1.9; 1.8)
MCH, pg -0.1 (-1.5; 1.4) -0.2 (-1.2; 1.2)
 0.1 (-0.6; 1.5) 0.1 (-1.2; 1.2)
MCHC, g/L -1 (-24; 14) -3 (-18; 15)
 0 (-8; 14) 0 (-12; 15)
Platelets, 7 (-34; 63) 5 (-57; 53)
 [10.sup.9]/L 5 (-34; 45) 11 (-58; 76)
Sedimentation 1 (-12; 14) 0 (-20; 19)
 rate, mm/h 0.2 (-3; 4) 0.3 (-2; 6)
TT, % -4 (-63; 60) -3 (-42; 76)
 -0.7 (-20; 9) -0.3 (-14; 16)

 [CV.sub.total] i
 %, mean
Analytes (maximum)

Leukocytes, 6.9 (16.9) 1.31
 [10.sup.9]/L 9.1 (21.3) 1.42
Neutrophils, % 4.3 (15.4) 1.35
 7.9 (22.6) 1.06
Lymphocytes, % 11.3 (39.5) 1.51
 10.1 (21.0) 1.20
Monocytes, % 11.2 (26.8) 1.22
 10.2 (59.0) 5.40 (f)
Eosinophils, % 16.0 (34.6) 1.76
 23.2 (63.2) 1.42
Basophils, % 92 (173) 3.05
 102 (173) 0.66
Erythrocytes, 2.6 (6.7) 1.17
 [10.sup.12]/L 1.4 (4.3) 0.70
Hemoglobin, 2.7 (6.6) 1.11
 g/L 1.5 (4.3) 1.33
Hematocrit, 2.8 (6.6) 1.04
 vol. 1.5 (4.7) 1.13
 fraction
MCV, fL 0.7 (1.6) 1.17
 0.5 (1.3) 1.03
MCH, pg 0.9 (2.6) 1.32
 0.7 (2.9) 1.93
MCHC, g/L 1.2 (3.7) 1.29
 0.9 (2.5) 1.06
Platelets, 5.8 (22.5) 0.99
 [10.sup.9]/L 4.2 (9.5) 1.45
Sedimentation 11.6 (35.2) 2.04
 rate, mm/h 12.4 (49.5) 2.74
TT, % 6.3 (27.2) 3.09
 3.1 (8.3) 1.23

 [[CV.sub.anal], [[CV.sub.total],
Analytes % (level) [[CV.sub.anal],

Leukocytes, 1.2 (6.9) 5.8
 [10.sup.9]/L 7.6
Neutrophils, % 1.0 (58.2) 4.3
 7.9
Lymphocytes, % 1.9 (27.1) 5.9
 5.3
Monocytes, % 4.5 (11.1) 2.5
 2.0
Eosinophils, % 7.1 (2.8) 2.3
 3.3
Basophils, % 23.1 (0.8) 4.0
 4.4
Erythrocytes, 0.8 (4.46) 3.3
 [10.sup.12]/L 1.8
Hemoglobin, 0.5 (125) 5.4
 g/L 3.0
Hematocrit, Calc. value
 vol.
 fraction
MCV, fL 0.6 (85.3) 1.2
 0.8
MCH, pg Calc. value

MCHC, g/L Calc. value

Platelets, 3.1 (316) 1.9
 [10.sup.9]/L 1.4
Sedimentation ND
 rate, mm/h
TT, % 1.65 3.8
 1.9

(a) n = 51 for outpatients; n = 51 for inpatients.

(b) Statistical analysis was performed with ANOVA for repeated
measurements and the Scheffe test. The multicomparison significance
level is at 99%.

(c) S1, blood specimen collected at 0800, fasting; [[DELTA].sub.(2-1),
change between blood specimen collected at 0930, after breakfast, and
S1; [[DELTA].sub.(3-1), change between blood specimen collected at
1100 and S1; i, index of heterogeneity; IN, inpatients; OUT,
outpatients; calc., calculated; MCV, mean cell volume; MCH, mean
corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin
concentration; ND, not determined; TT, thromboplastin time.

(d) Significant change between sample taken at 1100 and S1.

(e) Significant change between sample taken at 0930 and S1.

(f) Removing outliers gives i <1.80.

Table 2. Serum components obtained from the same subjects (a) during
the morning.

Analyte Mean, S1 (b)

Total calcium, mmol/L IN 2.24
 OUT (c,d) 2.34
Potassium, mmol/L IN 4.3
 OUT (d) 4.1
Sodium, mmol/L IN (c,d) 140
 OUT (c,d) 143
Creatinine, [micro] mol/L IN 100
 OUT (c,d) 90
ASAT, U/L IN 38
 OUT 21
ALAT, U/L IN 41
 OUT (c,d) 24
ALPP, U/L IN 176
 OUT (c,d) 140
GT, U/L IN 61
 OUT (d) 27
CK, U/L IN 239
 OUT 120
CK-B, U/L IN 8
 OUT 5
Glucose, mmol/L IN (c,d) 7.0
 OUT (c,d) 4.9
Cholesterol, mmol/L IN 4.7
 OUT (c,d) 5.0
Triglycerides, mmol/L IN (d) 1.51
 OUT 1.30
Free [T.sub.4], pmol/L IN 17
 OUT (d) 16
TSH, mU/L IN (c,d) 2.01
 OUT (c,d) 2.13
[P.sub.i], mmol/L IN (c,d) 1.04
CRP, g/L IN 60

 Distribution of changes, mean
 (extreme values)

Analyte [[DELTA].sub.(2-1)] [[DELTA].sub.(3-1)]

Total calcium, mmol/L -0.01 (-0.15; 0.13) -0.01 (-0.16; 0.13)
 0.05 (-0.05; 0.16) 0.04 (-0.05; 0.17)
Potassium, mmol/L -0.1 (-1.1; 0.6) 0.1 (-0.9; 0.9)
 0.1 (-0.6; 0.7) 0.1 (-0.5; 0.6)
Sodium, mmol/L -1 (-7; 2) -1 (-5; 3)
 1 (-2; 3) 1 (-3; 5)
Creatinine, [micro] mol/L 2 (-7; 34) 2 (-11; 34)
 -2 (-10; 4) -3 (-12; 2)
ASAT, U/L 0 (-21; 10) -1 (-42; 9)
 0 (-8; 4) 1 (-4; 18)
ALAT, U/L 0 (-15; 8) -1 (-21; 7)
 1 (-2; 6) 2 (-2; 8)
ALPP, U/L 1 (-19; 47) 0 (-32; 29)
 5 (-8; 20) 5 (-12; 32)
GT, U/L 0 (-10; 14) -1 (-21; 14)
 0 (-4; 4) 1 (-2; 4)
CK, U/L 11 (-78; 258) -3 (-139; 94)
 1 (-18; 42) -4 (-82; 12)
CK-B, U/L 1 (-3; 4) 0 (-7; 3)
 0 (-2; 2) 0 (-3; 3)
Glucose, mmol/L 1.9 (-2.0; 6.6) 0.7 (-4.2; 6.1)
 0.4 (-1.5; 4.0) 0.1 (-0.9; 1.0)
Cholesterol, mmol/L -0.05 (-1.0; 0.5) -0.10 (-1.0; 0.9)
 0.10 (-0.4; 1.2) 0.13 (-0.2; 1.6)
Triglycerides, mmol/L 0.02 (-0.57; 0.57) 0.09 (-0.57; 0.71)
 0.05 (-0.49; 0.85) 0.09 (-0.48; 0.74)
Free [T.sub.4], pmol/L 0.0 (-1; 9) 0.0 (-3; 2)
 -0.1 (-2; 2) -0.4 (-2; 2)
TSH, mU/L -0.25 (-2.25; 1.71) -0.39 (-2.29; 0.23)
 -0.62 (-2.90; -0.07) -0.65 (-3.31; 0.08)
[P.sub.i], mmol/L -0.08 (-0.46; 0.36) -0.05 (-0.47; 0.29)
CRP, g/L 0 (-20; 11) -1 (-17; 22)

 [CV.sub.total],
 %, mean
Analyte (maximum) i

Total calcium, mmol/L 1.8 (4.2) 0.95
 1.7 (3.8) 1.00
Potassium, mmol/L 4.5 (13.3) 1.24
 3.5 (8.7) 1.13
Sodium, mmol/L 0.8 (2.5) 1.28
 0.8 (1.8) 1.05
Creatinine, [micro] 3.8 (15.5) 2.40
 mol/L 2.7 (6.8) 1.07
ASAT, U/L 5.9 (15.7) 4.45
 4.9 (31.5) 4.55
ALAT, U/L 5.6 (16.5) 2.40
 5.4 (15.8) 1.76
ALPP, U/L 3.9 (10.0) 2.27
 3.1 (7.9) 1.47
GT, U/L 4.1 (12.4) 2.44
 3.4 (11.7) 1.37
CK, U/L 7.0 (27.7) 4.26
 3.8 (32.4) 4.18
CK-B, U/L 18.8 (86.6) 2.92
 16.2 (78.1) 1.00
Glucose, mmol/L 17.8 (37.0) 1.22
 11.2 (32.7) 1.89 (e)
Cholesterol, mmol/L 4.4 (11.1) 1.22
 2.8 (14.8) 2.39 (e)
Triglycerides, mmol/L 8.1 (21.2) 1.71
 9.5 (30.0) 1.79
Free [T.sub.4], 3.8 (13.0) 3.55
 pmol/L 3.2 (9.1) 0.98
TSH, mU/L 17.5 (57.8) 1.96
 24.0 (44.5) 1.88 (e)
[P.sub.I], mmol/L 9.0 (29.0) 1.4
CRP, g/L 7.6 (51.2) 1.34

 [CV.sub.anal], [CV.sub.total],:
Analyte %, (level) [CV.sub.anal]

Total calcium, mmol/L 1.29 (2.02) 1.4
 1.3
Potassium, mmol/L 0.98 (4.08) 4.5
 3.5
Sodium, mmol/L 0.28 (140.8) 2.9
 2.9
Creatinine, [micro] 1.71 (102.2) 2.2
 mol/L 1.6
ASAT, U/L 0.96 (47.3) 6.1
 5.1
ALAT, U/L 1.02 (48.6) 5.5
 5.3
ALPP, U/L 1.12 (212) 3.5
 2.8
GT, U/L 1.28 (104) 3.2
 2.7
CK, U/L 1.05 (235) 6.7
 3.6
CK-B, U/L 3.89 (8.1) 4.8
 4.2
Glucose, mmol/L 1.26 (6.65) 14.1
 8.7
Cholesterol, mmol/L 1.31 (5.47) 3.4
 2.1
Triglycerides, mmol/L 2.86 (0.98) 2.8
 3.3
Free [T.sub.4], 2.55 (15) 1.5
 pmol/L 1.3
TSH, mU/L 3.30 (2.00) 5.3
 7.3
[P.sub.I], mmol/L 1.94 (0.93) 4.6
CRP, g/L 2.76 (94) 2.8

(a) n = 51 for outpatients; n = 51 for inpatients. Statistical
analysis was performed as described in Table 1.

(b) S1, blood specimen collected at 0800, fasting; [[DELTA].sub.(2-1)],
change between blood specimen collected at 0930, after breakfast, and
S1; [[DELTA].sub.(3-1)], change between blood specimen collected at
1100 and S1; i, index of heterogeneity; IN, inpatients; OUT,
outpatients; ASAT, aspartate aminotransferase; ALAT, alanine
aminotransferase; ALPP, alkaline phosphatase; GT,
[gamma] -glutamyltransferase; CRP, C-reactive protein; [P.sub.i],
inorganic phosphate.

(c) Significant change between specimen taken at 0930 and S1.

(d) Significant change between specimen taken at 1100 and S1.

(e) Removing outliers gives i <1.80.

Table 3. Comparison of the individual CVs obtained from three
measurements in the morning with the experimentally (a) and
clinically derived (4) critical differences.

 of cases exceeding level of clinical significance

 Inpatients Outpatients

 Exp. (b) Clin. Exp. Clin.
 crit. crit. crit. crit.
Analyte difference difference difference difference

Leukocytes 0 8 0 20
Neutrophils 2 ND 4 ND
Lymphocytes 8 ND 0 ND
Hemoglobin 0 14 0 0
Hematocrit 0 10 0 0
Platelets 2 ND 0 ND
TT ND 6 ND 0
Potassium 0 8 0 0
Sodium 0 4 0 2
Creatinine 0 6 0 0
ASAT 4 2 2 2
ALAT 4 ND 2 ND
CK 2 ND 2 ND
CK-B 8 ND 4 ND
Glucose 0 76 4 46
Triglycerides 0 10 0 8
Free [T.sub.4] 0 4 0 2

 Experimentally Clinically
 derived derived
 critical critical
Analyte difference, % difference, %

Leukocytes 33.4 14.0-16.4
Neutrophils 18.8 ND
Lymphocytes 28.7 ND
Hemoglobin 8.0 4.9
Hematocrit 8.2 5.4
Platelets 19.8 ND
TT ND 15.2
Potassium 13.3 9.6
Sodium 2.4 1.7-2.7
Creatinine 10.6 10.1-19.8
ASAT 13.5 14.3-26.3
ALAT 15.2 ND
CK 24.0 ND
CK-B 40.1 ND
Glucose 37.9 11.2-17.2
Triglycerides 41.2 16.10
Free [T.sub.4] 17.0 8.3-28.7

(a) Derived from ultra-short-term variation and the 95% level for
individual changes (2, 3).F~cp., experimentally derived; crit.,
critical; Clin., clinically derived; ND, no data available; TT,
thromboplastin time; ASAT, aspartate aminotransferase; ALAT,
alanineaminotransferase.
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Title Annotation:Laboratory and Management
Author:Leppanen, Esa; Dugue, Benott
Publication:Clinical Chemistry
Date:Dec 1, 1998
Words:4989
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