Beruflich Dokumente
Kultur Dokumente
ORIGINAL ARTICLE
Department of Clinical
Biochemistry, Tepecik Training
and Research Hospital, Izmir,
Turkey
Correspondence:
Burak Toprak, Department of
Clinical Biochemistry, Tepecik
Training and Research Hospital,
Gaziler Cad., No:468, Yenisehir,
Izmir 35183, Turkey.
Tel.: +90-232-4696969;
Fax: +90-232-4330756;
E-mail: beiot@hotmail.com
doi:10.1111/ijlh.12158
S U M M A RY
Introduction: Anemia and macrocytosis are well-defined expected
hematologic findings of vitamin B12 and folate deficiency; however, some previous studies did not show a significant association
of subnormal B12 with anemia and macrocytosis.
Methods: We retrospectively analyzed 17 713 laboratory patient
records to evaluate vitamin B12 and folate levels in relation to
anemia and macrocytosis.
Results: In an age- and sex-adjusted logistic regression model, low
B12 status but not marginal B12 status was significantly associated
with anemia [ORs respectively, 1.291 (95% CI, 1.1821.410),
1.022 (95% CI, 0.9431.108)] and macrocytosis [ORs, respectively,
3.853 (95% CI, 3.1214.756), 1.031 (95% CI, 0.7701.381)]. Also
low folate status but not marginal folate status was significantly
associated with anemia [adjusted ORs, respectively, 1.819 (95% CI,
1.3722.411), 1.101 (95% CI, 0.9311.301)] and macrocytosis
[adjusted ORs, respectively, 2.945 (95% CI, 1.7474.965), 1.228
(95% CI, 0.7951.898)].
Conclusion: Our results show that increased anemia and macrocytosis are observed at values below commonly used B12 lower-reference thresholds. Determining a hematologic cutoff value may help
physicians in clinical practice.
INTRODUCTION
Vitamin B12 and folate are important cofactors in the
DNA synthesis. Deficiency of both of these water soluble vitamins is frequent health problems particularly
in the elderly [1, 2]. Common causes of cobalamin
deficiency are food-cobalamin malabsorbtion, pernicious anemia, and dietary deficiency [36]. A number
of biomarkers have been used for cobalamin deficiency diagnosis, including serum cobalamin,
2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 409414
methylmalonic acid (MMA), homocystein, and holotranscobalamin II. The most common biomarker used
for diagnosis is serum cobalamin. Older studies used
lower cobalamin cutoff values <90 pM (121 pg/mL)
for defining deficiency [7]. The cutoff value <148 pM
(200 pg/mL) was frequently used, and WHO suggested <150 pM (203 pg/mL) as a cutoff for defining
deficiency [8]. Utility of more sensitive biomarkers
MMA and homocystein showed that many patients
with normal cobalamin levels may be deficient;
409
410
M AT E R I A L S A N D M E T H O D S
We retrospectively analyzed serum folate, vitamin
B12, hemoglobin and MCV records of 1885 years
aged outpatients attending Tepecik Training and
Research Hospital during the period January 2007
December 2011. Only first results of the patients were
included in the study to exclude patients taking cobalamin or folate therapy. Four parameters investigated
were ordered by physicians in a 1-week period. The
results of 17 713 patients were included in the analysis. Tepecik Training and Research Hospital Ethics
Committee approved the study.
Serum vitamin B12 and folate were measured on
Immulite XPI 2000 system (Siemens Healthcare Diagnostics, Eschborn, Germany). MCV and hemoglobin
R E S U LT S
A total of 17 713 vitamin B12, folate, hemoglobin,
and MCV results were investigated. There were
12 870 female and 4843 male subjects. The results
show that 14.7% of the subjects have vitamin
B12 150 pg/mL (111 pM) and 34.1% have vitamin
B12 200 pg/mL (148 pM). Only 1.1% of the subjects
have folate 2.2 ng/mL (5 nM) and 4.7% have folate
3.0 ng/mL (6.8 nM). There were 35% anemic subjects, and 2.5% of the subjects have macrocytosis
(Table 1).
In an age- and sex-adjusted logistic regression
model, low B12 status but not marginal B12 status
was significantly associated with anemia [ORs, respectively, 1.291 (95% CI, 1.1821.410), 1.022 (95% CI,
0.9431.108)] and macrocytosis [ORs, respectively,
3.853 (95% CI, 3.1214.756), 1.031 (95% CI, 0.770
1.381)]. Low B12 status and marginal B12 status were
significantly related to male sex [age-adjusted ORs,
respectively, 1.300 (95% CI, 1.1831.427), 1.134
(95% CI, 1.0411.237)] (Table 2).
Also low folate status but not marginal folate status
was significantly associated with anemia [adjusted
2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 409414
DISCUSSION
411
49 18
27.3%
72.7%
14.7%
34.1%
1.1%
4.7%
35%
12.60 2.05
2.5%
84.7 9.8
Male
Anemia
Macrocytosis
Marginal
(n = 3439)
Low
(n = 2599)
Normal
(n = 11 675)
(%)
(%)
OR (95% CI)
(%)
OR (95% CI)
26.1
34.2
1.7
28
34.3
1.8
1.134 (1.0411.237)*
1.022 (0.9431.108)
1.031 (0.7701.381)
0.004
0.595
0.835
32.1
39.5
6.9
1.300 (1.1831.427)
1.291 (1.1821.410)
3.853 (3.1214.756)
<0.001
<0.001
<0.001
Normal B12 status was reference. Normal B12 (>200 pg/mL); marginal B12 (151200 pg/mL); low B12 (<151 pg/mL).
*Adjusted for age.
Adjusted for age and sex.
Anemia: hemoglobin <13 g/dL (men) <12 g/dL (women).
Macrocytosis: MCV > 100 fL.
2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 409414
412
26.6
34.8
2.4
Marginal
(n = 640)
Low
(n = 201)
(%)
OR (95% CI)
(%)
OR (95% CI)
42
35
3.6
2.026 (1.7202.386)*
1.101 (0.9311.301)
1.228 (0.7951.898)
<0.001
0.262
0.355
40.8
47.3
8.5
1.804 (1.3502.409)*
1.819 (1.3722.411)
2.945 (1.7474.965)
<0.001
<0.001
<0.001
Normal folate status was reference. Normal folate (>3 ng/mL); marginal folate (2.23 ng/mL); low folate (<2.2 ng/mL).
*Adjusted for age.
Adjusted for age and sex.
Anemia: hemoglobin <13 g/dL (men) <12 g/dL (women).
Macrocytosis: MCV > 100 fL.
Table 4. Low folate and vitamin B12 status in different age groups
Low vitamin B12
Low folate
Age
OR (95% CI)
OR (95% CI)
1850
5160
6170
7180
8185
13.8
14.2
14.4
17.7
19.4
1.0
1.033
1.048
1.338
1.500
1
0.8
1
1.7
2.7
1.0
0.815
0.959
1.725
2.705
(0.9151.167)
(0.9231.189)
(1.1831.513)**
(1.2211.843)**
(0.5171.286)
(0.6131.503)
(1.1872.507)*
(1.6064.556)**
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AU T H O R C O N T R I B U T I O N S
BT designed the study and wrote the paper. HZY
obtained data, drafted the paper, and provided critical
revisions. AC substantially contributed to analyses and
interpretation of the data.
2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 409414
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2013 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2014, 36, 409414