Serum Ferritin Levels In 41 Multiple-Transfused Sickle
Cell Patients at the Yaound¨¦ Central Hospital, Cameroon,
Africa: A Pilot Study
Claude
Tayou Tagny, Martine E Oloume, Bernard Chetcha, Dora Mbanya
Claude
Tayou Tagny, Martine E Oloume, Bernard Chetcha, Dora Mbanya, Faculty of
Medicine and Biomedical Sciences/University of Yaound¨¦ I, Cameroon
Claude
Tayou Tagny, Dora Mbanya, Department of Hematology and Blood Transfusion,
University Teaching Hospital Yaound¨¦, Cameroon
Bernard Chetcha, Department of Hematology and Medical
Oncology at the Yaound¨¦ Central Hospital, Cameroon
Correspondence to: Claude Tayou Tagny, Department of
Hematology and Blood Transfusion, University Teaching Hospital Yaound¨¦,
Cameroon.
Email: tayouclaude@yahoo.fr
Telephone: +237-93-060083
Received: December 25,
2014
Revised: January 25, 2015
Accepted: January 25, 2015
Published online: April 30, 2015
ABSTRACT
AIM: Serum ferritin is widely used to
assess iron load. Transfusion is usually indispensable in management of sickle
cell disease. Iron overload is a major factor associated with morbidity in
these patients when they benefit from repeated blood transfusions. We assessed
serum ferritin levels of multiple transfused sickle cell patients using an
Enzyme-Linked Immuno-Sorbent Assay in order to determine the frequency of hypo
and hyperferritinemia. C-reactive protein was determining to find an acute
inflammatory process.
Results: A total of 41
patients received a minimum of two blood transfusions. Their ages ranged from
15 to 59 years with a mean of 27.2¡À9.8 years. Females represented 64.3% of
patients. Each patient received about 2 to 18 red blood cell transfusions. All
patients received transfusion for anaemia management; serum ferritin levels
ranged from 31 to 1,255 µg/L, with high levels (>150 ¦Ìg/L for female and
>200 ¦Ìg/L for male) found in 46.3% of patients. In our study population
34.1% had normal C-reactive protein. There were 17% of patients with elevated
serum ferritin levels without an associated inflammatory process. Our study
showed weak correlation between ferritin levels and number of blood
transfusions in patients with normal CRP (r =0.02), as well as in the
whole studied population (r = 0.14).
Conclusion: Hyperferritinemia
is frequent in sickle cell disease patients having history of transfusion.
However, it does not seem to be associated to frequency of blood transfusions
in Cameroon.
© 2015 ACT. All
rights reserved.
Key words: Ferritin;
Transfusion; Sickle cell disease; Iron overload
Tagny CT, Oloume
ME, Chetcha B, Mbanya D. Serum Ferritin Levels In 41 Multiple-Transfused Sickle Cell Patients at
the Yaound¨¦ Central Hospital, Cameroon, Africa: A Pilot Study. International Journal of Hematology Research 2015; 1(1): 24-26
Available from: URL: http://www.ghrnet.org/index.php/ijhr/article/view/996
INTRODUCTION
Homozygous sickle cell disease (SCD) is an autosomal recessive genetic
disease that results from the substitution of valine for glutamic acid at
position 6 of the ¦Â-globin gene, leading to production of a defective form of
hemoglobin, hemoglobin S (HbS). It is the most frequent genetic disorder in the
world. In Cameroon the prevalence of sickle cell trait is about 25% and the
disease affects about 2% of the population[1]. This disorder is
still an incurable disease and improving the quality of life of those affected
remains a major challenge. Blood transfusion is an important element in the
management of sickle cell disease. It remains an essential component of care
for SCD, but associated complications include iron overload, transfusion
reactions, infections, acute lung injury, pain crisis, stroke,
immunomodulation, anaphylaxis, and alloimmunization. Transfused red cells will
significantly increase oxygen-carrying capacity, blood viscosity, potentially
reducing blood flow. However, it increases the risk of iron overload. Then,
iron overload is a major factor associated with morbidity in these patients
when they benefit from repeated blood transfusions, because the body has no
regulatory process for eliminating excess iron[2]. Serum ferritin is
the most accessible marker to explore of iron stores. This study was conducted
to assess ferritin levels of multiple-transfused sickle cell in order to
determine the frequency of hypo and hyperferritinemia. The relation of serum
ferritin to iron load estimated from transfusion history was examined.
METHODS
It was a descriptive and cross-sectional study. Sickle cell patients
were targeted for this study. Selection criteria were all patients who ever
received more than two blood transfusions. Patients were recruited from Monday
to Saturday during two months (January-February 2013) in the hematology and
oncology department of the Yaound¨¦ Central Hospital, Cameroon. It was a
consecutive sampling. All patients who fulfilled selection criteria were
included in the study. The minium sample size of this study was determined
based on the prevalence of
hypoferritinemia reported by Hafsia & al[2]. The
exclusion criteria were: non-consent, the lack of medical records, patients
whose last transfusion was less than three months, vaso-occlusive crisis that
occurred during or within eight days of blood collection, a fever during
sampling (temperature>38¡ãC), undocumented transfusions, bleeding disorders,
pregnant women, and documented liver disease. Medical records and a
questionnaire were used to investigate transfusion history. To calculate the
amount of iron received, 1 mL of red blood cells was estimated to contain 1 mg
of iron[3]. Patient weights were recorded. To calculate transfusion
iron load, cumulative iron load received was divided by the weight.
4 mL of venous
blood was collected in a dry tube. This was to determine serum ferritin by
enzyme immunoassay (ELISA Biorex United kingdom ISO 13485), and C-reactive
protein (CRP) by latex particle agglutination. These laboratory tests were
performed in the hematology laboratory of the University Teaching Hospital of
Yaound¨¦, Cameroon. We considered normal range of serum ferritin between 15-200 ¦Ìg/L
for male and 15-150 ¦Ìg/L for female.
Each
participant signed a consent form at the recruitment. The national Ethical
committee provides a clearance for this study as well as the Central Hospital
of Yaound¨¦. Statistical analyzes were performed using Epi Info 6 software, SPSS
12 (Statistical Package for the Social Sciences) and Microsoft Excel 2007. The
correlation between ferritin levels and the volume of transfusions received was
tested using the Pearson correlation coefficient "r". The statistical
significance was set at 5%.
RESULTS
A total of 41 patients were recruited. The age ranged between 15 and 59
years, with an average age of 27.2¡À9.8 years. Female gender was the most
represented (64.3%). Each patient received between 2 and 18 transfusions since
their births. The date of the last transfusion was between March 2005 and
September 2012. All patients received whole blood transfusion mainly to deal
with severe anemia. Hemoglobin levels during the last transfusion ranged
between 2.9 and 5.8 g/dL with a mean of 4.4¡À0.8 g/dL. Sixteen patients had
received 1 to 3 sessions of exchange transfusions during pregnancy, stroke,
cardiomyopathy and priapism. Only one patient had exchange transfusion twice to
prevent stroke. The evaluation of iron administered in transfusions varies
between 500 and 4,500 mg/per patient, with an average of 1,774¡À960 mg, knowing
that blood bag contains approximately 250 mg of iron (250 mL red blood cells).
The estimating cumulative iron load received was divided by the weight. It
appears that patients received doses ranging from 7.2 mg/kg to 76.0 mg/kg, with
an average of 31.4¡À17.6 mg/kg. Serum ferritin levels ranged from 31 to 1,255 ¦Ìg/L.
High serum ferritin levels (>150 ¦Ìg/L for female and >200 ¦Ìg/L for male)
were found in 19 patients (46.3%). CRP was negative (<6 mg/L) in 14 patients
(34.1%). It was found that 7 patients (17%) had high ferritin levels without an
associated acute inflammatory process, with values ranged from 242 to 1,240 ¦Ìg/L.
This study shows weak correlation between serum ferritin levels and number of
transfusions received in patients with a negative CRP (r =0.02) (Figure
1, table 1).
DISCUSSIONS
Sickle cell disease causes a chronic hemolytic anemia generally well
tolerated; blood transfusions are used mainly in case of severe anemia[4].
If the goal is an acute reduction in the proportion of sickled red cells in
addition to an increase in oxygen-carrying capacity, exchange transfusion is
the therapy of choice. The indications for exchange transfusion include acute
stroke, acute chest syndrome with severe hypoxia, acute multi-organ failure,
and possibly acute severe priapism. Partial exchange transfusion is indicated
for hemoglobin SC patients undergoing major surgery. Transfusion requirements
in sickle cell patients have not been established precisely in
resources-limited context, although in practice, blood transfusion seems to be
frequent. This is due to a lack of traceability and h¨¦movigilance data related
to poor documentation and archiving.
The female
gender was predominant in our study. This female predominance also found in the
study of Hafsia et al[2] emphasizes the hypothesis that
female sickle cell patients could be more transfused, since in addition to
chronic hemolytic anemia, menstrual blood loss and pregnancy increase iron
needs. However, these observations were not evident in the current study.
Hemoglobin levels were all very low when patients were transfused. Indeed,
severe anemia has been reported to be one of the most frequent condition
related to blood transfusion during
sickle cell anemia crisis[5]. Only sixteen patients had
received 1 to 3 sessions of exchange transfusions. This is probably due to the
lack of equipment and the fact that exchange transfusion requires large amounts
of blood products.
Iron stores
are normally saturated after 20 transfusions or 5,000 mL of red blood cells[6],
which corresponds to an intake of 5,000 mg of iron. Here, the maximum volume
was 4,500 mL of packed RBC, or 4,500 mg of iron brought to the body. It means
that in theory, none of the patients had an iron overload, although high
ferritin levels were found. The estimate of the iron intake based on the weight
gives the maximum value of 76.0 mg/kg. Complications of iron overload appear at
doses of 400 to 500 mg/kg[7].
Iron stores in
the body are mainly in the form of ferritin. The references values are 15-200 ¦Ìg/L
for men, and 15-150 ¦Ìg/L in women[8]. Normally ferritin presents a
close correlation with iron stores. According to World Health Organization
recommendations on the interpretation of serum ferritin during inflammatory
processes[8], none of patients had an iron deficiency.
The mechanism
is different in inflammation and infection, where the iron is transferred
directly from hemoglobin to reticulo-histiocytic reserves, serum ferritin may
be normal or even increased[9]. It is also an acute phase protein
and increases in inflammatory process. It complicates the analysis of normal or
elevated serum ferritin values in areas where infectious or inflammatory
diseases are widespread. In the absence of inflammation or liver disease, high
serum ferritin level indicates iron overload[10]. The lack of
exploration of liver function does not suggest those results are only due to
transfusions. Ferritin increases significantly with CRP (r =0.57).
When we
excluded individuals with acute inflammation (CRP>6 mg/L), it remains seven
patients with high ferritin levels. However sickle cell anemia is a disorder
with common inflammatory processes. Such an exclusion mechanism could
artificially weaken high ferritin levels. It emerged naturally weak correlation
between serum ferritin and blood volume received (r =0.14) in the whole
population. It is the same result in patients with a negative CRP (r
=0.02). This goes against the results indicated by Hafsia et al in which
a significant strong correlation (r =0.74) was found. Nevertheless our
results are similar to the study of Hamartz et al[10] in who
assessed 20 sickle cell patients with chronic transfusions.
In fact, this
study found weak correlation between serum ferritin and the number of
transfusions (r =0.30, p=0.200), although the results of liver
biopsy iron stores increase with the duration of transfusion. Similarly, in the
study of Brown et al concerning 27 children subjected to chronic transfusions
without chelating therapy[11], there was no correlation between
serum ferritin and volume of transfusions, although the correlation between the
volume of transfusions and liver iron concentration was established. However, a
study done by Fung et al[12] on 199 sickle cell transfused
patients and 64 non-transfused SCD has noted a significant difference in serum
ferritin (3459 mg/L) in the first group versus 90 mg/L. Multiple transfusions
lead undeniably increased iron stores. But this lack of correlation highlights
the limitations of serum ferritin as a faithful marker of iron stores,
especially in sickle cell disease in which hemolysis influences iron
metabolism. We have not assessed serum ferritin level according to period of
transfusion in this pilot study since patients were transfused in a very
irregular intervals.
Hyperferritinemia is frequent in sickle cell disease patients having
history of transfusion. However, it does not seem to be associated to frequency
of blood transfusions in Cameroon. Hyperferritinemia should be assessed in all
patients with past history of multiple transfusions regardless of number of
transfusions received.
ACKNOWLEDGMENTS
Our sincere thanks go to the place
of all those who contributed to this study, and in particular: To all sickle
cell patients who agreed to the study, the team of the Department of Hematology
and Medical Oncology at the Yaound¨¦ Central Hospital, all the staff of
Hematology and Blood Transfusion Service of the University Hospital Yaound¨¦.
CONFLICT OF INTERESTS
The authors have no conflicts of interest to declare.
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Peer reviewers: Ernesto de Meis, Universidade Federal do Rio de Janeiro
Campus Maca¨¦ -Av. do Alo¨ªzio, 50 - Granja dos Cavaleiros, Maca¨¦ - RJ, Brazil;
Imen MOUMNI, Laboratory of Molecular and Cellular Hematology, Pasteur Institute
of Tunis, Tunisia; Olufemi AKODU, P.O.Box 11950, GPO Ikeja, Lagos, Nigeria.
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