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International Journal of Laboratory Hematology

The Official journal of the International Society for Laboratory Hematology

ORIGINAL ARTICLE INTERNAT IONAL JOURNAL OF LABORATO RY HEMATO LOGY

Empty iron stores in children and young adults—the diagnostic


accuracy of MCV, MCH, and MCHC
A. E. 
ASBERG*, G. MIKKELSEN † , M. W. AUNE ‡ , A. 
ASBERG †

*Department of Pediatrics, S U M M A RY
Trondheim University Hospital,
Trondheim, Norway Introduction: Erythrocyte mean cell volume (MCV) is used clinically

Department of Clinical to classify anemia, and normal values may be used to exclude iron
Chemistry, Trondheim
University Hospital, Trondheim, deficiency. We have studied the diagnostic accuracy of MCV and
Norway the related measures mean cell hemoglobin (MCH) and mean cell

Department of Immunology hemoglobin concentration (MCHC) in diagnosing empty iron stores
and Transfusion Medicine,
in children and young adults.
Trondheim University Hospital,
Trondheim, Norway Methods: Diagnostic accuracy of MCV, MCH, and MCHC was studied
by ROC curve analysis in 6443 ambulant patients aged 0.5–
Correspondence: 25 years, of which 476 were anemic. In all patients, blood hemoglo-
Ann Elisabeth  Asberg, Depart- bin, MCV, MCH, and serum ferritin were measured in specimens
ment of pediatrics, St. Olavs
Hospital, 7006 Trondheim, sampled at the same time. MCHC was calculated as MCH divided by
Norway. MCV. The gold standard of empty iron stores was s-ferritin <10, 15,
Tel.: +47 72574846; or 20 lg/L. The cutoff limit of MCV giving 90% sensitivity in diag-
Fax: +47 72575501;
nosing serum ferritin <15 lg/L was constructed using quantile
E-mail: ann.asberg@stolav.no
regression.
doi:10.1111/ijlh.12132
Results: Generally, MCH was slightly more accurate than MCV and
MCHC. In the whole study population, the area under the ROC
Received 5 March 2013; curve was 0.68–0.93 for MCV, 0.73–0.96 for MCH, and 0.68–0.87
accepted for publication 9 July for MCHC; and 0.70–0.86, 0.71–0.89, and 0.68–0.88, respectively,
2013 in the anemic subpopulation. At the cutoff limits of MCV giving a
sensitivity of 90% at all ages in anemic patients, the specificity was
Keywords
about 50%.
Erythrocyte indexes,
hypochromic anemia, iron Conclusion: Mean cell hemoglobin, MCH, and MCHC are only mod-
deficiency anemia, mean cell erately accurate in diagnosing empty iron stores in children and
volume, mean corpuscular young adults, and normal values of these tests do not exclude
hemoglobin, mean corpuscular
empty iron stores in anemic patients.
hemoglobin concentration

of iron-deficient children have iron deficiency anemia,


INTRODUCTION
which is supposed to be microcytic [2]. Reading diag-
Iron deficiency is common in children in Norway [1] as nostic guidelines, one gets the impression that iron
well as in other parts of the world [2]. About one-third deficiency anemia is always microcytic [3,4], although

98 © 2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 98–104
A. E. 
ASBERG ET AL. | DIAGNOSTIC ACCURACY OF ERYTHROCYTE INDEXES 99

we have known for decades that it may very well be specimens on either Abbott CELL-DYN 4000, Siemens
normocytic [5]. In fact, the diagnostic accuracy of Bayer ADVIA 120 or ABX Micros 60, with reagents
mean cell volume (MCV) in diagnosing iron deficiency from the manufacturers. Sysmex XE-2100 was the
is fairly moderate in adults with anemia [6] and very main instrument; however, in certain cases, when
little investigated in children. In this study, we evalu- the main instrument did not yield valid results for
ated the diagnostic accuracy of MCV in diagnosing some parameters, another instrument would be used.
empty iron stores in Norwegian children and young The laboratory secured that b-hemoglobin, MCV, and
adults with and without anemia, using s-ferritin as the MCH from the different instruments were directly
gold standard. We compared the diagnostic accuracy of comparable, using fresh blood specimens analyzed on
MCV and the related measures mean cell hemoglobin Sysmex XE-2100 to calibrate the other instruments.
(MCH) and mean cell hemoglobin concentration Specimens from three patients were assayed on each
(MCHC). instrument every weekday to check agreement
between the instruments. On the Sysmex XE-2100,
b-hemoglobin was measured using the sodium lauryl
METHODS
sulfate (SLS)-hemoglobin method with a calibrator
traceable to the reference method recommended by
Population
the International Council for Standardization in Hae-
We used laboratory data from the Clinics of Laboratory matology (ICSH). B-hematocrit was measured using
Medicine at Trondheim University Hospital. These labo- the erythrocyte aperture–impedance pulse height
ratories serve nearly all inpatient and outpatient activi- detection method, MCV was calculated as b-hemato-
ties in the hospital and receive specimens from primary crit divided by blood erythrocyte particle concentra-
care physicians and other healthcare facilities for outpa- tion, MCH as b-hemoglobin divided by blood
tients in the County of Sør-Trøndelag. The hospital is a erythrocyte particle concentration, and MCHC as MCH
tertiary care centre for about 6 88 000 inhabitants and divided by MCV. MCV was calibrated with a calibrator
a secondary care centre for about 2 98 000 inhabitants. traceable to reference methods that follow the recom-
Specimens sent to the hospital for analysis are mostly mendations of ICSH and The Clinical and Laboratory
from primary care centers. Standards Institute (CLSI) standards for MCV. Using
We collected data between October 10, 2005, and Sysmex XE-2100, we have previously found MCV to
March 19, 2012, from ambulant patients that were be sufficiently stable in specimens kept at room tem-
<25 years old at the time of specimen sampling and perature (20 °C) for 14 h. If pre-analytical storage time
kept only records for patients with complete data sets exceeded 14 h, MCV was analyzed using the instru-
on serum ferritin (s-ferritin), blood hemoglobin ment ABX Micros 60. In this way, MCV could be reli-
(b-hemoglobin), MCV, and MCH analyzed in speci- ably analyzed in specimens kept at room temperature
mens sampled at the same time. Then all duplicate for up to 48 h. Between-day coefficients of variation
records were deleted, so that the data file only con- for b-hemoglobin, MCV, and MCH were 0.8% at
tained one (the oldest) record for each individual. 12.3 g/dL, 0.8% at 82 fL, and 0.9% at 28 pg/L, respec-
Finally, to secure that as many as possible of the tively. In classifying patients as anemic, we used the
records represented a new clinical event and not a following local b-hemoglobin lower reference limits
control situation, we deleted all records from 2005 (in g/dL) in healthy persons: 0–1 days, 14.5; 1–2 days,
and 2006. As a result, the record used for all patients 14.0; 2–7 days, 14.3; 1–2 weeks, 13.5; 2–4 weeks,
was the first record to satisfy the criteria since October 10.8; 1–2 months, 9.0; 2–12 months, 10.0; 1–4 years,
2005, so even for patients registered with a record 10.5; 4–8 years, 10.8; 8–14 years, 11.1; girls >14 years,
from January 2007, at least 14 months had gone. 11.7; boys >14 years, 13.4. For MCV, MCH, and
MCHC, we used the following local lower reference
limits in healthy persons: MCV (in fL): 0–5 days, 95;
Laboratory analysis
5 days-2 months, 87; 2–12 months, 72; 1–7 years, 75;
B-hemoglobin, MCV, and MCH were mostly analyzed 7–14 years, 77; >14 years 82. MCH (in pg): 0–7 days,
on Sysmex XE-2100 (Sysmex, Kobe, Japan) and few 31.0; 1–4 weeks, 28.0; 1–2 months, 29.0; 2–4 months,

© 2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 98–104
100 A. E. 
ASBERG ET AL. | DIAGNOSTIC ACCURACY OF ERYTHROCYTE INDEXES

27.0; 4–12 months, 24.0; 1–4 years, 23.9; 4–12 years,

(32–35)

(32–35)

(32–35)

(32–36)

(32–36)
MCHC
24.1; 12–18 years, 25.0; >18 years, 27.1. MCHC (in g/
dL): 0–2 months, 25.8; 2 months-4 years, 27.1;

33

34

34

34

34
Table 1. Population characteristics for age groups of 5-year intervals. Median values are given for s-ferritin (lg/L), b-hemoglobin (b-Hb) (g/dL),
4–9 years, 30.6; 9–12 years, 31.2; >12 years, 31.7.

(23–29)

(25–30)

(25–31)

(26–32)

(27–32)
All biochemical analyses were carried out on a

MCH
Roche Modular P system (Roche Diagnostics GmbH,

27

28

28

30

30
Mannheim, Germany), with reagents from the manu-
facturer (s-ferritin, s-iron and s-transferrin and s-CRP)

(71–85)

(76–88)

(76–90)

(78–93)

(82–94)
and Diagnostic Systems GmbH, Holzheim, Germany

MCV
(s-CRP). S-ferritin was measured using a ‘sandwich’

79

82

84

87

88
immunological method with electrochemilumines-
cence detection. The calibrator was traceable to WHO

(10.6–13.4)

(11.5–14.3)

(11.9–15.1)

(13.0–16.6)

(13.7–16.9)
Ferritin 80/602 First International Standard. Between-
day coefficients of variation were 6.9% at 5.0 lg/L

B-Hb
and 4.1% at 50 lg/L.

12.1

12.8

13.5

14.8

15.2
All analyses were monitored using appropriate
internal and external quality control systems.

(20–191)

(35–318)
Males (n = 2450)

(12–94)

(14–84)
S-ferritin

(9–85)
MCV (fL), MCH (pg), and MCHC (g/dL). The number in parenthesis is 5 and 95 percentiles
Statistical analysis

120
26

34

37

67
The diagnostic accuracy of the various tests was stud-

189

352

508

667

734
ied using receiver operating characteristic (ROC) curve

n
analysis [7]. We did separate ROC curve analysis for

(31–35)

(32–35)

(32–35)

(31–35)

(32–35)
females and males, using different cutoff values of
MCHC

s-ferritin, 10, 15, and 20 lg/L, as gold standards for 33

34

34

33

33
empty iron stores. These analyses were repeated in
the subgroup of anemic patients. We made 12 statisti-
(21–29)

(25–30)

(25–31)

(24–32)

(25–32)
cal comparisons between the diagnostic accuracy of
MCH

different tests, so we considered P-values <0.05/


27

28

29

29

30
12 = 0.0042 as statistically significant. To investigate
the influence of age and gender on certain percentiles
(69–85)

(75–89)

(78–92)

(77–94)

(78–95)
of MCV in anemic patients, we used quantile regres-
MCV

sion with multivariable fractional polynomials [8] to


80

83

85

88

89

find the simplest nonlinear transformation (if any) of


continuous variables. Medians were compared using
(10.2–13.5)

(11.4–14.0)

(11.3–14.6)

(11.0–14.7)

(11.2–14.8)

the Wilcoxon rank sum (Mann–Whitney) test. For all


statistical analyses, we used the Stata software (http://
B-Hb

12.1

12.9

13.3

13.3

13.3

www.stata.com/), version 12.


The study was approved by The Regional Commit-
Females (n = 3993)

tee for Medical and Health Research Ethics (case no


(6–109)

(7–129)
(11–99)
S-ferritin

(8–82)

(8–94)

2012/160/REK midt).
26

33

32

33

38

R E S U LT S
107

289

601

1273

1723

Characteristics of the study population of 6 443


n

patients are given in Tables 1 and 2. S-CRP was mea-


10–14

15–19

20–24

sured in 1 460 patients and was <10 mg/L in 1321


Age

0–4

5–9

(90.5%). Median s-ferritin was 42 lg/L in the group

© 2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 98–104
A. E. 
ASBERG ET AL. | DIAGNOSTIC ACCURACY OF ERYTHROCYTE INDEXES 101

Table 2. The number of patients with anemia and s-ferritin below 10, 15, and 20 lg/L is given for age groups of 5-
year intervals. The number in parenthesis is percentages of total for each interval

Females (n = 3993) Males (n = 2450)

S-ferritin below S-ferritin below

Age Total Anemia 10 lg/L 15 lg/L 20 lg/L Total Anemia 10 lg/L 15 lg/L 20 lg/L

0–4 107 9 (8.4) 9 (8.4) 21 (19.6) 35 (32.7) 189 7 (3.7) 10 (5.3) 24 (12.7) 46 (24.3)
5–9 289 9 (3.1) 8 (2.8) 25 (8.7) 49 (17.0) 352 5 (1.4) 7 (2.0) 26 (7.4) 53 (15.1)
10–14 601 31 (5.2) 34 (5.7) 75 (12.5) 124 (20.6) 508 52 (10.2) 12 (2.4) 26 (5.1) 59 (11.6)
15–19 1273 127 (10.0) 134 (10.5) 215 (16.9) 334 (26.2) 667 56 (8.4) 12 (1.8) 23 (3.5) 32 (4.8)
20–24 1723 153 (8.9) 146 (8.5) 240 (13.9) 361 (21.0) 734 27 (3.7) 6 (0.8) 14 (1.9) 14 (1.9)

Table 3. Diagnostic accuracy of MCV, MCH, and MCHC in diagnosing empty iron stores in all 6443 patients

Area under the ROC curve (95% confidence


Number of patients interval)
Limit of s-ferritin
defining empty With empty Without empty
iron stores iron stores iron stores Total MCV MCH MCHC

Females
<10 lg/L 331 3662 3993 0.810 0.857* 0.819
(0.782–0.838) (0.834–0.881) (0.794–0.845)
<15 lg/L 576 3417 0.741 0.787* 0.729
(0.718–0.765) (0.766–0.808) (0.705–0.754)
<20 lg/L 903 3090 0.680 0.725* 0.682
(0.660–0.702) (0.706–0.745) (0.661–0.703)
Males
<10 lg/L 47 2403 2450 0.929 0.959* 0.865
(0.902–0.956) (0.943–0.975) (0.804–0.926)
<15 lg/L 113 2337 0.805 0.847* 0.744
(0.760–0.851) (0.811–0.884) (0.697–0.791)
<20 lg/L 204 2246 0.804 0.834* 0.685
(0.774–0.834) (0.809–0.859) (0.645–0.724)

*The area under the ROC curve of MCH is statistically significantly larger than the area under the ROC curve of the
second most accurate test (P < 0.002).

of 1 321 patients with s-CRP <10 mg/L compared females and males, MCH had a statistically sign-
with 65 lg/L in the 139 patients with higher s-CRP ificantly larger area under the ROC curve than the
(P < 0.0001). Median s-ferritin was 40 lg/L in those second most accurate test (P < 0.002 for all compari-
4983 patients, where s-CRP was not measured, not sons). All tests showed a better diagnostic accuracy in
significantly different from the group with s-CRP males than in females. Table 4 gives corresponding
<10 mg/L (P = 0.19). S-creatinine was measured in results for the anemic subpopulation of 476 patients.
4565 patients and found to be normal in 4539 In this subpopulation, MCH showed better diagnostic
(99.4%). accuracy than the second most accurate test in all
Table 3 gives the area under the ROC curve of groups, but the differences did not reach statistical
MCV, MCH, and MCHC for three cutoff values of the significance.
gold-standard s-ferritin in the whole study population. In the anemic subpopulation of 476 patients, using
For all definitions of empty iron stores and in both the lower, age-specific reference limits as cutoff limits,

© 2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 98–104
102 A. E. 
ASBERG ET AL. | DIAGNOSTIC ACCURACY OF ERYTHROCYTE INDEXES

Table 4. Diagnostic accuracy of MCV and MCH in diagnosing empty iron stores in the subgroup of 476 anemic
patients

Area under the ROC curve


Number of patients (95% confidence interval)
Limit of s-ferritin
defining empty With empty Without empty
iron stores iron stores iron stores Total MCV MCH MCHC

Females
<10 lg/L 178 151 329 0.757 0.774 0.726
(0.702–0.811) (0.721–0.826) (0.671–0.780)
<15 lg/L 208 121 0.719 0.737 0.700
(0.659–0.780) (0.678–0.796) (0.643–0.758)
<20 lg/L 230 99 0.700 0.714 0.680
(0.633–0.768) (0.649–0.780) (0.618–0.742)
Males
<10 lg/L 29 118 147 0.856 0.894 0.881
(0.790–0.923) (0.843–0.946) (0.814–0.947)
<15 lg/L 40 107 0.790 0.823 0.805
(0.709–0.872) (0.745–0.902) (0.726–0.884)
<20 lg/L 49 98 0.766 0.792 0.756
(0.685–0.847) (0.714–0.870) (0.674–0.837)

the sensitivity and specificity (95% confidence


DISCUSSION
interval) of MCV were 71.8% (66.2–77.4%) and
66.7% (60.5–72.8%), respectively, when empty iron Eighty years after its introduction [9], MCV is still
stores were defined as s-ferritin <15 lg/L. The corre- used to classify anemia into micro-, normo- and mac-
sponding figures for MCH were 71.4% (65.7–77.0%) rocytic forms, while MCH and MCHC are seldom
and 74.1% (68.4–79.8%), and for MCHC 51.6% mentioned in this context. We show that MCH gener-
(45.4–57.8%) and 82.9% (78.0–87.8%), respectively. ally is more accurate than MCV in diagnosing empty
Figure 1 shows the 90 percentile of MCV of anemic iron stores, while MCHC is less accurate. Interestingly,
patients with empty iron stores defined as s-ferritin the tests are less accurate in the subpopulation of ane-
<15 lg/L. Choosing the 90 percentile as cutoff limit mic patients where they are supposed be most useful
for diagnosing empty iron stores implies choosing a (Table 4). In fact, MCV, MCH, and MCHC are only
sensitivity of 90%. The 90 percentile increases from moderately accurate in diagnosing empty iron stores
78 fL in children at 1 year of age to 90 fL in adults at in the anemic subpopulation, with an area under the
25 years of age. The lower reference limits are below ROC curve of 0.7–0.8 when empty iron stores are
the 90 percentiles at all ages, indicating a lower than defined as s-ferritin <15 lg/L. For MCV, our findings
90% sensitivity if the lower reference limits are used are close to the results found by Guyatt in a meta-
as cutoff limits. Also shown in Figure 1 is the 50 per- analysis of 436 anemic patients above 18 year of age
centile of MCV in anemic patients without empty iron where iron deficiency was determined by bone mar-
stores, which is close to the 90 percentile of MCV in row examination [6]. They estimated the area under
anemic patients with empty iron stores. Choosing a the ROC curve for MCV to be 0.76.
sensitivity of 90% therefore implies choosing a speci- When using MCV to classify anemia, we ought not
ficity of about 50%. These percentiles were not statis- to falsely classify iron-deficient anemic patients as iron
tically significantly associated with neither gender nor replete. Normal MCV does not exclude iron defi-
an interaction factor between gender and age, and ciency, as shown by Beutler several decades ago [5]
there was no statistically significant nonlinear associa- and verified also in our study where values from
tion with age. many patients with empty iron stores are higher than

© 2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 98–104
A. E. 
ASBERG ET AL. | DIAGNOSTIC ACCURACY OF ERYTHROCYTE INDEXES 103

definitive tests. Our study was not designed to evalu-


ate whether MCV is a useful criterion for deciding on
further tests.
Why MCH performed better than MCV in our
study is not clear and a bit surprising. MCH may be a
more robust measure, depending on b-hemoglobin
and b-erythrocytes, which both are accurate and
precise, while MCV may increase during prolonged
specimen storage before analysis [11]. However, this
problem should be minimized by the standard proce-
dures in the laboratory (Materials and Methods). Any-
way, the difference between the diagnostic accuracy
of MCV and MCH was small, which is to be expected
given the close correlation between the two measures
Figure 1. MCV in 248 anemic patients with empty (spearman correlation coefficient of 0.872 in this
iron stores (green dots) and 227 anemic patients population).
without empty iron stores (red dots) plotted against Likewise, we have no explanation why MCV, MCH,
age. Empty iron stores were defined as s-ferritin and MCHC were more accurate in males than females,
<15 lg/L. The upper green line is the 90 percentile a phenomenon not mentioned in the meta-analysis of
of MCV in patients with empty iron stores, while the
Guyatt et al.[6] This phenomenon seems to be age
red line is the 50 percentile of MCV in patients
without empty iron stores. The stepped black line dependent, as we found no differences between boys
indicates lower reference limits of MCV in healthy and girls below 10 years of age (data not shown).
persons above 6 months. Choosing the 90 percentile We used s-ferritin as a gold standard to determine
(upper green line) as cutoff limit for empty iron empty iron stores and tried different cutoff values
stores means choosing a sensitivity of 90%. The 90
between 10 and 20 lg/L. In this range of cutoff values,
percentile in patients with empty iron stores is close
to the 50 percentile in patients without empty iron s-ferritin is a rather specific and less sensitive test [6]. It
stores, indicating that a cutoff limit with 90% may be argued that s-ferritin is not a valid gold stan-
sensitivity has close to 50% specificity. The results dard, because it increases in several inflammatory con-
from one patient without empty iron stores and ditions. We did find a higher median s-ferritin in the
MCV of 124 fL were omitted from the figure. 139 patients with elevated s-CRP. However, the
patients in this study were ambulant, and s-CRP was
<10 mg/L in 90% of those examined, so most of them
the lower reference limit (Figure 1). To exclude empty probably did not have any inflammation. Furthermore,
iron stores, ideally the sensitivity should be 100% and median s-ferritin in the majority with no s-CRP result
definitely not <90%. The decision limit giving 90% was not statistically significantly different from those
sensitivity, that is, the 90 percentile in the population with normal s-CRP. Also s-ferritin may have less accu-
with empty iron stores is above the normal lower ref- racy in patients with kidney failure, but more than
erence limits (Figure 1). However, higher sensitivity 99% of the patients had normal s-creatinine. At the
comes at the cost of lower specificity, which is about moment, s-ferritin is the single best test for diagnosing
50% because the 90 percentile of MCV in anemic iron deficiency when iron content in bone marrow is
patients with empty iron stores is quite close to the 50 used as a gold standard [6]. Even bone marrow iron
percentile of anemic patients without empty iron may not always reflect the storage iron [12,13]. Any-
stores (Figure 1). In adults, Seward et al.[10] found way, s-ferritin was the only gold standard that could be
that MCV at a cutoff limit of 88 fL had a sensitivity of applied in this study. For MCV, MCH, and MCHC the
88% and specificity of 39% in diagnosing s-ferritin diagnostic accuracy increased as the gold-standard limit
<15 lg/L. Their findings are similar to ours, and they decreased, probably because a more stringent (lower)
concluded that MCV was not sufficiently accurate to limit isolated a more severely iron-deficient population.
be a useful criterion for the selection of more We used a s-ferritin limit of 15 lg/L when estimating

© 2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 98–104
104 A. E. 
ASBERG ET AL. | DIAGNOSTIC ACCURACY OF ERYTHROCYTE INDEXES

the percentile functions of MCV in anemic patients. local lower b-hemoglobin reference limit of healthy
This choice was somewhat of a compromise, as we persons as cutoff limits to define anemia. These lim-
thought 10 lg/L might be too low (low sensitivity) and its may not be applicable in other populations and
20 lg/L might be too high (low specificity). Using bone health care systems.
marrow iron as the gold standard, Hallberg et al.[14] In conclusion, MCV, MCH, and MCHC are only
found that s-ferritin ≤15 ug/L was the optimal limit for moderately accurate in diagnosing empty iron stores
an assay calibrated against WHO Ferritin 80/602 First in children and young adults. These tests are no more
International Standard. accurate in anemic than in nonanemic patients. It
The findings in this clinical population may not should once again be pointed out that normal values
be transferable to other populations. First, the popu- of MCV, MCH, and MCHC do not exclude empty iron
lation is mostly northwest European, with a very stores in anemic patients.
low prevalence of thalassemia, so iron deficiency is
by far the most prevalent cause of microcytic
AC K N OW L E D G E M E N T S
anemia. In a population with an appreciable num-
ber of thalassemia, MCV, MCH, and MCHC may We thank Frode Width Gran for valuable assistance
show even lower accuracy. Secondly, we used the with data extraction.

REFERENCES diagnosis of iron-deficiency anemia: an the hematology analyser used: a stability


overview. J Gen Intern Med 1992;7:145– study with Bayer Advia 120, Beckman
1. Hay G, Sandstad B, Whitelaw A, Borch- 53. Coulter LH 750 and Sysmex XE 2100. Clin
Iohnsen B. Iron status in a group of 7. Metz CE. Basic principles of ROC analysis. Chim Acta 2008;397:68–71.
Norwegian children aged 6-24 months. Semin Nucl Med 1978;8:283–98. 12. Ganti AK, Moazzam N, Laroia S, Tendulkar
Acta Paediatr 2004;93:592–8. 8. Royston P, Sauerbrei W. Building multivar- K, Potti A, Mehdi SA. Predictive value of
2. Mahoney DH. Iron deficiency in infants iable regression models with continuous absent bone marrow iron stores in the clin-
and young children: screening, prevention, covariates in clinical epidemiology–with an ical diagnosis of iron deficiency anemia. In
clinical manifestations, and diagnosis. In: emphasis on fractional polynomials. Meth- Vivo 2003;17:389–92.
UpToDate. Basow DS (ed). Waltham: UpTo- ods Inf Med 2005;44:561–71. 13. Thomason RW, Almiski MS. Evidence that
Date, 2012. 9. Wintrobe MM. Classification of the Anemias stainable bone marrow iron following par-
3. Janus J, Moerschel SK. Evaluation of ane- on the Basis of Differences in the Size and enteral iron therapy does not correlate with
mia in children. Am Fam Physician Hemoglobin Content of the Red Corpuscles. serum iron studies and may not represent
2010;81:1462–71. Proc Soc Exp Biol Med 1930;27:1071–3. readily available storage iron. Am J Clin
4. Irwin JJ, Kirchner JT. Anemia in chil- 10. Seward SJ, Safran C, Marton KI, Robinson Pathol 2009;131:580–5.
dren. Am Fam Physician 2001;64:1379– SH. Does the mean corpuscular volume 14. Hallberg L, Bengtsson C, Lapidus L, Lind-
86. help physicians evaluate hospitalized stedt G, Lundberg PA, Hulten L. Screening
5. Beutler E. The red cell indices in the diag- patients with anemia? J Gen Intern Med for iron deficiency: an analysis based on
nosis of iron-deficiency anemia. Ann Intern 1990;5:187–91. bone-marrow examinations and serum fer-
Med 1959;50:313–22. 11. Imeri F, Herklotz R, Risch L, Arbetsleitner ritin determinations in a population sample
6. Guyatt GH, Oxman AD, Ali M, Willan A, C, Zerlauth M, Risch GM, Huber AR. Sta- of women. Br J Haematol 1993;85:787–98.
McIlroy W, Patterson C. Laboratory bility of hematological analytes depends on

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