Blood Transfusion, Serum Total Iron Binding Capacity and Iron in

Hemodialysis Patients Margono Soekarjo Hospital

Vitasari Indriani

, Aditiawarman

, Yunanto Dwi Nugroho

and Fania Salsabila

Departement of Clinical Pathology, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Indonesia

Department of Internal Medicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Indonesia

3Student of Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Indonesia

Keywords: Chronic kidney disease, hemodialysis, serum iron, TIBC, transfusion

Abstract: In the final stages, chronic kidney disease (CKD) patients require renal replacement therapy like hemodialysis

(HD). Packed Red Cell (PRC) transfusion is an anaemia management therapy that can increase serum Total

Iron Binding Capacity (TIBC) and iron levels. This study analyzed blood transfusions, TIBC serum and iron

serum levels in hemodialysis patients with repeated transfusions at Margono Soekarjo Hospital to assess the

value of TIBC in the iron excess and deficiency diagnosis. An observational analytic design with cross-

sectional findings was used. We investigated 85 hemodialysis patients; (73.3% men and 26.7% women aged

20 to 70 years) visited hemodialysis clinics from January 2018 to 2020. Correlation studies showed a linear

relationship between the number of blood transfusions and the level of iron serum in hemodialysis patients

(value 𝑃: 0.0001), a positive correlation between the number of blood transfusions and TIBC serum

concentration (value 𝑃: 0.04); the significant relationship between TIBC serum and iron serum (value: 0.003).

The prevalence of excess iron was 10.6%, and 2.3% in iron deficiency. Non-iron therapy patients with a

maximum of one transfusion with iron therapy, patients with transfusions who are not on iron therapy, and

patients on oral iron therapy were compared. The Kruskal-Wallis test showed that iron levels varied

significantly between groups (𝑃 value: 0.0001). TIBC serum is not a reliable marker of excess iron. For

patients with regular transfusions, periodical checking of TIBC and iron serum is recommended.

1 INTRODUCTION

Chronic kidney disease (CKD) is a worldwide public

health problem with a high prevalence and an

increasing incidence every year. CKD is the 27th

cause of death in the world in 1990 and increased to

18th in 2010. According to (Hall 2016), globally, the

prevalence of CKD is 13.4% for stage 1-5 patients

and 10.6% for stage 3- patients 5 (Hall et al., 2016;

Urrechage et al., 2013). In Malaysia, 18 million

people, an estimated 1800 new kidney failure cases

per year. The Ministry of Health (2017) reports that

CKD's prevalence reaches 12.5% in Indonesia's adult

population. In Central Java, CKD's prevalence

reached 0.3% of Central Java's population (Depkes,

2017)

https://orcid.org/0000-0001-8563-1781

https://orcid.org/0000-0003-1786-211X

https://orcid.org/0000-0002-7104-7901

https://orcid.org/0000-0002-2825-2571

CKD patients with hemodialysis generally have

low Hb levels, and anaemia is not uncommon. The

indication for transfusion in CKD patients is anaemia

with a Hb level <7 g / dL. CKD anaemia occurs due

to erythropoietin (EPO) deficiency, decreased

intestinal iron absorption, iron deficiency, and iron

loss during HD. During hemodialysis, there is

frequent hemodynamic instability and decreased

oxygen perfusion to body tissues due to a sudden

decrease in blood volume during blood filtration.

CKD also decreases catecholamine hormones'

sensitivity because the damaged kidneys cannot clear

the blood vessels' hormone. The results in a decrease

in heart rate. Combining these two things will reduce

the stroke volume, resulting in hypoperfusion of

organs (McGuire et al., 2018). Hemoglobin is the

284

Indriani, V., Aditiawarman, ., Nugroho, Y. and Salsabila, F.

Blood Transfusion, Serum Total Iron Binding Capacity and Iron in Hemodialysis Patients Margono Soekarjo Hospital.

DOI: 10.5220/0010491502840288

In Proceedings of the 1st Jenderal Soedirman International Medical Conference in conjunction with the 5th Annual Scientiﬁc Meeting (Temilnas) Consortium of Biomedical Science Indonesia

(JIMC 2020), pages 284-288

ISBN: 978-989-758-499-2

blood's oxygen carrier. If the levels decrease, there

can be a decrease in the oxygenation of the body's

organs. Anaemia with a Hb level that is too low (<7 g

/ dL) puts CKD patients at high risk for doing HD

because the patient's hemodynamic function becomes

increasingly unstable, so it is too risky to do HD

(Hider et al., 2013; Kdigo, 2012).

One of the treatments for anaemia in CKD is by

transferring Packed Red Cell (PRC) components so

that the patient's Hb level increases. In the body, after

one erythrocyte life cycle, iron is released from heme.

If it is excess, iron will be stored in the endoplasmic

reticulum tissue as ferritin and hemosiderin, but the

body does not have an active iron secretion system.

As the amount of PRC transfused increases, the serum

iron accumulates. The results in less transferrin,

which is not bound by iron. Simultaneously, levels of

non-transferrin bound iron (NTBI) increased. It can

cause excess iron (Gao et al., 2014).

Chronic renal failure is often associated with

Renal anaemia due to iron-restricted erythropoiesis

(Hall et al., 2016; Urrechaga E., 2013). Kidneys

secrete erythropoietin, a protein that is involved in

erythropoiesis. The secretion of erythropoietin

decreases when kidneys are damaged, resulting in

renal anaemia (Depkes, 2017). Because iron is also

required for erythropoiesis, iron deficiency may also

cause anaemia (Depkes 2017; McGuire et a., 2018).

The principal means to treat renal anaemia in most

settings are Blood transfusion, erythropoietin (EPO),

and iron therapy (Hider et al., 2013; Kdigo, 2012).

Renal anaemia correction in chronic renal failure

patients could carry a risk for iron overload (Gao et

al., 2014; Thavarajah et al., 2019) and increase the

risk of adverse events such as hypertension,

congestive heart failure, myocardial infarction, and

vascular access thrombosis (Depkes, 2019; Milic et

al., 2016). Correction of renal anaemia to be done by

blood transfusions and iron therapy. Although

transfusions are considerably safer nowadays

(Bozhuizen et al., 2019), transfusion reactions must

be prevented as a risk in blood transfusion therapy

(Robinson et al., 2017; Tanhehco et al., 2012; Gao et

al., 2014). These risks include transmission of

infectious agents (robinson et al., 2017; Alla et al.,

2016; Rerambiah et al, 2014), the development of

alloimmunization (Tagny et al., 2013; Baby et al.,

2010) and iron overload (Esther et al., 2018). The

present study aimed to evaluate iron status in patients

with renal failure undergoing hemodialysis and assess

the value of Total Iron Binding Capacity (TIBC) in

diagnosing iron overload and iron deficiency in an

RSUD Prof Dr. Margono Soekarjo Hospital.

2 MATERIALS AND METHODS

We investigated 85 hemodialysis patients (73.3%

male and 26.7% female aged 22 to 73 years) who

attended Prof. Dr. Margono Soekarjo Hemodialysis

Center Hospital from January 2018 to January 2020,

using cross-sectional studies. Patients were divided

into four (4) groups; (1) patients with none or single

transfusion without iron therapy; (2) patients with

none or single under iron therapy; (3) polytransfused

patients without iron therapy; (4) polytransfused

patients with iron therapy. Blood samples were taken

before the hemodialysis session. 3 mL of venous

blood was collected in straight tubes. The collected

blood samples were then centrifuged (3000 rpm for

15 minutes. Iron and TIBC in the serum used Cobas

c501 to interpret. Table 1 shows TIBC and iron

concentration ranges in the serum and interpretation

of the results. Characteristics data and research

variables showed in the form of descriptive analysis.

The independent variables are including blood

transfusion and iron serum. The independent variable

of this study is TIBC.

We used the Spearman test to assess the

correlation between the number of transfusions, iron,

and TIBC levels. The strength of TIBC and iron

serum concentrations compatibility was assessed

based on the Kappa coefficient (𝜅) that was calculated

using the formula 𝜅 = (𝑃𝑜 − 𝑃𝑒)/1 − 𝑃𝑒, where 𝑃𝑜 is

the relative observed agreement among assessor and

𝑃𝑒 is the theoretical probability of chance agreement.

The groups' discrepancy was analyzed using the

Kruskal-Wallis multiple comparison test Dunn's post-

test to assess therapeutic effectiveness. 𝑃 value below

5% was considered as significant. Regarding ethics,

the health research ethics committee of RSUD Prof

Dr. Margono Soekarjo Number 420/01030/I/2020

approved the study. Besides, all patients consented to

participate in the study.

3 RESULTS

It can be seen in Table 1 that the distribution of iron

and TIBC levels and their interpretation in the study

sample population. Univariate analysis can be seen in

Table 2. It is found that most gender is male. The most

blood group is the patient with blood group B, and the

most age group is the patient aged 51-60 years. Figure

1 shows that the number of PRC units received by

CKD patients undergoing HD by repeated

transfusions is 2 - 14, with a maximum average of 4

Blood Transfusion, Serum Total Iron Binding Capacity and Iron in Hemodialysis Patients Margono Soekarjo Hospital

285

kolf. Correlation between transfusion, TIBC, and Iron

levels are shown here.

Table 1. TIBC and Iron range in the serum and

interpretations.

Iron

deficienc

Normal

Iron

overloa

Serum

TIBC

>400µg/dL

245-

400

µg

/dL

<245µg/dL

Serum

Iron

<35µg/dL

35-

140

µg

/dL

˃140µg/dL

Data showed a positive and significant correlation

between the number of transfusions and TIBC levels

(Spearman 𝑟: 0.65; 𝑃 value: 0.0001). Although it was

weak, the correlation between the number of

transfusions and iron serum levels was positive and

significant (Spearman 𝑟: 0.32; 𝑃 value: 0.03).

Table 2. Research Characteristics

Characteristics

N=85 %

Gender

Male 53 73.3

Female 32 26.7

Blood type

A 25 33.3

B 28 33.3

AB 10 11.1

O 22 22.2

Age (year)

–

30 6 7.1

–

40 5 5.8

–

50 29 34.1

–

60 37 43.5

–

70 6 7.1

> 70 2 2.4

Further correlation analysis showed a significant

relationship between TIBC and iron serum

concentration (Spearman 𝑟: 0.32; 𝑃 value: 0.003).

However, the observed Spearman 𝑟 coefficient

suggested that the correlation between TIBC serum

and iron serum concentrations is weak, although

significant. Next is the correlation between TIBC and

Iron serum in excess iron cases. Table 3 shows the

distribution of patients according to TIBC and their

iron levels in this study. The prevalence of excess iron

based on TIBC serum was 46.06%. The prevalence of

excess iron was 15.7% when it was assessed based on

the iron serum levels. The prevalence of excess iron

based on TIBC and the iron concentration in serum

was 10.6%. The prevalence of iron deficiency based

on TIBC serum was 17.4%, while iron deficiency

based on iron serum concentration was 8.9%. The

prevalence of iron deficiency in both TIBC and iron

concentration is 3.3%.

Table 3. Patients Distribution according to their TIBC and

iron levels in serum

Total Iron Binding Capacit

Iron

deficienc

normal Iron

Overloa

Total

Iron

Deficienc

3 5 7 15

Normal 15 19 26 60

Iron

Overloa

1 5 8 14

Total 19 29 41 89

Cohen's Kappa (𝜅) formula used in this study with

0.14 𝜅 coefficient. As a result, the correlation between

TIBC and iron levels in the serum was considered

weak or inadequate. Regarding transfusion, TIBC,

and Iron serum, a comparison was made on patients

in groups 1 and 2 to patients in groups 3 and 4. The

"Kruskal-Wallis test" showed that TIBC levels varied

significantly between the groups (𝑃 value: 0.0001).

Besides, "Dunn's Multiple Comparison Test" also

showed that (1) on patients without iron therapy,

TIBC level was significantly higher in polytransfused

patients than patients with none or single transfusion

(𝑃 value: 0.0001), (2) on patients under iron therapy,

the TIBC level was significantly higher in

polytransfused patients than on patients who had none

or single transfusion (𝑃 value < 0.05), (3)

polytransfused patients on iron therapy had

significantly higher levels of TIBC compared to

patients who had none or one transfusion and without

iron therapy (𝑃 value: 0.001), and (4) polytransfused

patients who were not on iron therapy had

significantly higher levels of TIBC compared to

patients who had none or single transfusion and who

were under iron therapy (𝑃 value < 0.05).

Table 4. Discrepancy between groups

Grou

1 20 < 0.001

2 21

3 22

4 22

Comparing the same groups of patients for their

serum iron concentrations, the "Kruskal-Wallis test"

showed no significant differences between the groups

(table 4).

JIMC 2020 - 1’s t Jenderal Soedirman International Medical Conference (JIMC) in conjunction with the Annual Scientiﬁc Meeting

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286

Figure 1 Distribution of data on the number of respondent

PRC units

4 DISCUSSION

The present study aimed to evaluate iron status in

patients with renal failure undergoing hemodialysis

and assess the value of TIBC in the diagnosis of

excess iron and iron deficiency. In developing

countries such as Indonesia, TIBC serum level in

patients is often used as a marker for excess or

deficiency iron diagnosis in hemodialysis patients.

This is because iron-binding capacity is the

transferrin's capacity to bind with iron. When iron

stores are depleted, the transferrin levels increase in

blood. As only one-third of transferrin is saturated

with iron, so the transferrin present in serum has an

extra binding capacity (67%). It is called unsaturated

iron-binding capacity (UIBC). TIBC is the total of

iron serum and UIBC. Iron status in hemodialysis

patients monitored using serum TIBC may rarely be

performed by hemodialysis service personnel

because confounding factors such as acute, chronic

inflammation, and malnutrition can cause different

TIBC serum value interpretation (Gujja et al., 2010).

This study showed an intense positive linear

relationship between the number of blood

transfusions with TIBC serum levels. It also indicated

a weak association between the number of blood

transfusions and iron concentrations in the serum.

The compatibility level between TIBC and iron levels

in the serum was low. The data suggest that multiple

transfusions increase TIBC serum substantially and at

lower iron serum levels. We found that in

hemodialysis patients, TIBC serum is strongly

overestimated iron level. TIBC serum also

overestimates iron deficiency cases, but on a lower

level. In this study, the prevalence of excess iron

based on TIBC serum was 42.3, whereas the

prevalence of excess iron based on iron serum levels

was 21.2%. The prevalence of iron deficiency based

on TIBC serum and iron serum was, respectively,

17.4% and 10.6%. Based on the data, 65% of patients

had moderately high TIBC serum levels, and 67% of

patients with very high TIBC levels had their iron

serum level within the normal range. High TIBC

serum is not a reliable marker of excess iron (Petkova

et al., 2019; Pfeiffer et al., 2017). Because the use of

TIBC serum as a marker for excess iron or deficiency

could lead to (1) holding iron therapy in patients that

need it and (2) giving iron treatment to patients who

do not require it, accurate assessment of the body iron

load is essential to prevent iron toxicity and to

manage iron chelation therapy. Although we did not

assess liver iron concentration (LIC) by magnetic

resonance imaging (MRI), based on the published

report (Depkes, 2017; Milic et al., 2018; Hoffbrand et

al., 2012).

The Anemia monitoring due to retention in

dialyzers was not possible in this study. This study

also did not monitor the nutritional intake and diet

consumed by patients. The type of food consumed by

the patient can affect iron serum levels. Red meat is

the most effective food (40%) absorbed by the

intestine because it is a heme iron source.

Consumption of vitamin C also increases the

absorption of iron in the intestines.

Meanwhile, intake containing calcium and

tannins inhibits iron absorption, thereby reducing

serum iron levels. Therefore, this can be a

confounding factor in this study. The suggestion is to

do similar research by controlling for confounding

factors such as nutritional intake, Erythropoiesis

Stimulating Agents (ESAs) therapy. Future research

will use the cohort method to see the disease's course

and the effect of transfusion on iron levels in a more

usual manner. We would suggest patients under

regular transfusion therapy to do TIBC and iron

serum measurement periodically in these countries.

5 CONCLUSIONS

TIBC serum is not a reliable marker of excess iron.

For patients with regular transfusions, periodical

checking of TIBC and iron serum is recommended.

ACKNOWLEDGEMENTS

The author would like to acknowledge RSUD Prof

Dr. Margono Soekarjo hemodialysis centre for giving

access to the medical record and hemodialysis

patients.

Blood Transfusion, Serum Total Iron Binding Capacity and Iron in Hemodialysis Patients Margono Soekarjo Hospital

287

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JIMC 2020 - 1’s t Jenderal Soedirman International Medical Conference (JIMC) in conjunction with the Annual Scientiﬁc Meeting

(Temilnas) Consortium of Biomedical Science Indonesia (KIBI )

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