A clinicopathological study of severe non-haemolytic
anemia in age group of 0-18 years
Deka
R.1, Hazarika P.2
1Dr. Rasadhar Deka,
Associate Professor, 2Dr. Prabir Hazarika,
Assistant Professor, both authors are affiliated with Department of Pathology,
JMCH, Jorhat, Assam, India
Address for
Correspondence: Dr. Rasadhar Deka, Associate Professor,
Department of Pathology, JMCH, Jorhat, Assam. E-mail: rasadhar.deka@gmail.com
Abstract
Introduction: Anaemia
is typically defined as reduction in the haemoglobin concentration below
certain value.The normal reference value of haemoglobin concentration defined
by W.H.O. is 12.5gm/dl for men and women. Evaluation of the causes of severe
non haemolytic anaemia seems to be important as the various causes would
respond to different treatment modalities. Methods:
This was a hospital based prospective study that was carried out in a
tertiary referral centre for one year, from January to December 2014. A total
of fifty cases were subjected for thorough clinical examination and various
investigations in order to provide information to evaluate their causes. Results: The maximum numbers of cases
were reported in the age group of 3-6 years with male predominance. The maximum
number of cases were diagnosed as Iron Deficiency Anaemia (22%); followed by
Acute Lymphoblastic Leukaemia (20%), Acute Myeloblastic Leukaemia (16%),
Megaloblatic Anemia (16%), Aplastic Anemia (10%), Anemia of Chronic Disease
(8%). Conclusion: Evaluation of the
causes of non haemolyticanemia seems to be important because different causes
would respond to different treatment modalities; thus enabling the physician to
plan out a successful therapeutic outline.
Key words: Clinicopathological,
Severe anaemia, Non-haemolytic, Paediatric age, Haematological malignancies.
Introduction
Anemia,
by modern simple definition, is a condition characterised by an abnormal
reduction in body’s total red cell mass [1]. As routine measurement of red cell
mass is not always easy, anemia is typically defined as reduction in the
haemoglobin concentration below certain value. The normal reference value of
haemoglobin concentration defined by W.H.O. is 12.5gm/dl for men and women [2].
Anemia is accordingly classified as-
10.0-11.9gm/dl—mild
anemia
07.0-09.9gm/dl—moderate
anemia
‹
07.0gm/dl—severe anemia [3]
Anemia
in the group 0-18 years occupies a numerically important group of diseases
which is leading a high morbidity and mortality [4]. Therefore, rapid and
accurate diagnosis of paediatric anemia, including haematological malignancies
have an increasing importance because an early and accurate diagnosis and
treatment can reduce morbidity and can save many lives.
Manuscript
received: 02nd November 2018
Reviewed: 12nd
November 2018
Author Corrected: 17th November 2018
Accepted for
Publication: 23th November 2018
If the easily diagnosable blood loss and
hemolytic group of anemia are excluded, the nutritional deficiency is the
leader of severe anemia. Thus, Iron Deficiency Anemia, Megaloblastic Anemia,
Aplastic Anemia, the malignant diseases including leukaemia, lymphoma and anemia
of chronic diseases are the distinct causes of non haemolyticanemia [5,6,7].
Keeping in mind all the facts
delineated, the present study had been undertaken- to analyse the different
causes of severe non haemolytic anemia among the children of 0-18 yrs with
their relative incidence.
Materials and Methods
Study
design: This is a hospital based prospective study. This
study was conducted with 50 patients of age 0-18 years referred from the
paediatric and medical units of a tertiary referral centre with clinical
presentation of severe anemia.
Aim and Objectives
a) To
evaluate the different causes and incidence of severe non haemolytic anemia
among the age group 0-18 years.
b) To
make an analytical study of important clinical presentation and the
haematological findings in different pattern of anemia.
Exclusion
criteria: Patients with obvious blood loss, haemolytic group
of anemia and patients with haemoglobin concentration of 7 gm/dl and above were
excluded from this study.
A provisional diagnosis based on clinical
findings was recorded. Complete haematological examination was done including
bone marrow and additional examinations (where necessary) - Serum iron
estimation, vitamin B12 & folate estimation, serum billirubin, Hb
electrophoresis, Pearl’s stain cytological stain and BM trephine biopsy were
included.
FNAC & histopathology for cervical
and abdominal mass and radiological studies like Chest X-ray, USG, CT scan etc.
were done in selected cases.
MGG stain was done for PBS and BM
examination. MPO, PAS were used as cytochemical stain in BM aspiration.
Results
A total of fifty cases were subjected
for thorough investigations. The most common physical finding apart from pallor
was hepatomegaly and fever. Majority of the patients in the study were male in
the age group of 3-6 years (28%).
Table-1:
Demographic distribution of
cases
Age in
years |
Male |
Female |
No of
cases |
Percentage |
0 to 3 |
7 |
0 |
7 |
14.00 |
3+ to 6 |
6 |
8 |
14 |
28.00 |
6+ to 9 |
2 |
3 |
5 |
10.00 |
9+ to 12 |
4 |
6 |
10 |
20.00 |
12+ to 15 |
3 |
2 |
5 |
10.00 |
15+ to 18 |
4 |
5 |
9 |
18.00 |
Total |
26 |
24 |
50 |
100 |
The
majority of the cases were between the age group of 3 to 6 years, followed by
the group between 9 to 12 years.Between 0-3 years of age no female cases were
found. In this study male slightly outnumbered the female.
Table-2:
Haemoglobin level of the
cases
Hb level
(gm/dl) |
Number of cases |
Percentage (%) |
‹ 3 |
5 |
10 |
3 to ‹ 5 |
16 |
32 |
5 to ‹ 7 |
29 |
58 |
Total |
50 |
100 |
Majority
of the cases had haemoglobin level between 5 to ‹ 7 gm/dl and 5 cases had
haemoglobin level below 3gm/dl.
The causes of anemia under this study
were found as –Iron deficiency anemia -22% cases, Acute lymphoblastic
leukaemia-20%, Acute myeloblastic leukaemia-16%, Megaloblastic anemia-16%,
Aplastic anemia-10%, Anemia of chronic diseases-8%, Juvenile CML-04% ,
Lymphoma-04% and Anemia of mixed deficiency -02%.
Aetiology |
No of Cases |
Percentage (%) |
IDA |
11 |
22.0 |
Megaloblastic Anemia |
08 |
16.0 |
Mixed Deficiency Anemia |
01 |
02.0 |
Aplastic Anemia |
05 |
10.0 |
Anemia of chronic diseases |
04 |
08.0 |
Acute LymphoblaticLeukemia |
10 |
20.0 |
Acute Myeloblastic Leukemia |
08 |
16.0 |
Juvenile Chronic Myelocytic Leukemia |
02 |
04.0 |
Lymphoma–NHL |
02 |
04.0 |
Total |
50 |
100.0 |
It
was found that iron deficiency anemia was the most common cause of severe non
haemolytic anemia followed by malignant causes (ALL). Among the non malignant
cases iron deficiency anemia was followed by megaloblastic anemia and aplastic
anemia. And in malignant group acute lymphoblaticleukemia was the leader; followed by acute
myeloblastic leukemia.
Discussion
In developed countries, a steady decline
in prevalence of anemia in childhood age has been observed [8]. A study
conducted in 2001-2002 in Nindura Block, Barabanki District, North India found
severely anemic children in 3 subcentres as 2.73%; 2.25% and 5.29% [9].
In another study, done by Deeksha Kapur
et al (2001) found severe anemia as 7.8% among children. In this study, the
severely anemic patients were found 8.5% within the specified age group.
A peak incidence of age distribution was
found to be similar as compared to other studies like Harbans Lal et al and
Sharma D K et al which showed 3-6 years
as the commonest and second commonest age group respectively [10, 11].
Studies conducted worldwide, sex
incidence varied from place to place. Hasanbegovic E et al found 49.33% male
and 50.67% female. Similarly Rahim Fazlur et al found 66.27% male and 33.73%
female which corresponds well to our study [12, 13].
Amongst the non malignant haematological
disorders, nutritional anemia constituted 44% of which IDA is the most common
(22%), followed by megaloblastic anemia (16%) and 2% cases had mixed deficiency
causes.Similar observations were found by other authors.
White K. C et al (2005) found IDA as the
major cause. In Amritsar, Harbans Lal et al studied 210 cases and found IDA as
the major cause (24.5%) [14,15].
Regarding Megaloblastic anemia, Gera et
al found 7.8% and Choudhury et al found 27.1% and present study concordance
with these two results (16%) [16,17].
Incidence of Aplastic anemia were
18.7% and 12.8% in two separate studies
done by Fazlur et al (2005) and S.P. Shah et al (1999) which is slightly higher
than the present study [18]. This may be due to higher sample number and better
facilities of BM evaluation.
Among the 44% of malignant causes of
anemia, ALL is the most common (20%) followed by AML (16%) JCML (4%) and NHL
(4%).
Fazlur et al reported 23.6% ALL, and
08.4% AML [19]. In a separate study by Vandana Jain et al ALL cases found in
27.2% and AML in 04% cases [20]. The higher incidence of AML in our study may
be due to the higher age range.
In a comparative study with Fazlur R et
al found Megaloblastic anemia to be most common followed by Aplastic anemia. In
our study IDA is found to be most common cause followed by Megaloblastic anemia
among non malignant causes.
The difference of the incidence may be
due to factor like geographic variation, bigger sample size and age variation.
This study is conducted in an area with more BPL population where nutritional
deficiency is more common. More cases of Aplastic anemia could have been
diagnosed had BM biopsy been undertaken.
Among the malignant causes slightly
higher incidence in AML than the Fazlur R et al study is found. But similar
findings with that of Dube et al is found.
And about JCML and NHL, the incidence is almost similar to the findings
of the other workers.
Table-3: Showing correlation between
provisional clinicaldiagnosis andconsistency with haematological diagnosis
Hematological
Diagnosis (No. of cases) |
Provisional
clinical Diagnosis (No of cases) |
Number of
consistent cases |
Number of
inconsistent cases |
IDA(11) |
Severe anemiawith hepatosplenomegaly–(2) Nutritional anemia– (9) |
9 |
2 |
Megaloblastic Anemia(7) |
?Viral encephalitis with severe anemia– (1); Severe anemia with hepatosplenomegaly and bleeding
manifestation– (1) Severe anemia with hepatosplenomegaly -(2); Nutritional anemia– (3) |
3 |
4 |
Mixed Defi. Anemia (1) |
Severe anemia. ? Nutritional with viral
hepatitis-(1) |
1 |
0 |
Anemia of Chronic Disease (4) |
Anemia of chronic diseases– (3) TB intestine with nutritional anemia(1) |
3 |
1 |
Aplastic Anemia(5) |
Severe anemia for evaluation– (3) Anemia of nutritional origin– (2) |
3 |
2 |
ALL (10) |
Anemia with lymphadenopathy and hepatosplenomegaly –
(9) Severe anemia with hepatomegaly – (1) |
9 |
1 |
AML (8) |
Anemiawith hepatosplenomegaly andbleeding
manifestation |
8 |
0 |
NHL (2) |
Anemia with generalized lymphadenopathy
andhepatosplenomegaly-(2) |
2 |
0 |
Juvenile CML (2) |
Severe anemiawithhepatosplenomegaly and
lymphadenopathy-(2) |
2 |
0 |
Percentage of accuracy of
provisional clinical diagnosis in the diagnosis of severe on
haemolytic anemia by haematological analysis:
Total
Anemia Cases (studied) :
50
Consistent
Results
:
40
Inconsistent
Results
:
10
Percentage
of Accuracy :
80%
Fig-1A: IDA-PBS
of a 6 Yrs Boy shows Severe Hypochromia with Poikilocytosis, Numerous
Microcytic Cells with Adequate Platelets and White Blood Cells (Case 3). Fig 1B-PERL’S
STAIN- Bone Marrow Smear of a 10 Yrs Boy showing Perls’ Stain in a Diagnosed
Case of JCML with Score ‘2’ (normal iron particles, Case 49)
Fig-2: MA Bone Marrow
Picture of a 14 Yrs Boy Shows Numerous Basophilic and Orthochromatic
Megaloblasts with Open Lacy Chromatin (Case 30)
Fig-3A:
AML
M1 BM smear of an 11 Yrs Girl Shows Blast Cells with Large, Somewhat Irregular
Nuclei with 1 or more Nucleoli. Cytoplasm Is Eccentric and Mostly Agranular.
Very Few Cells Showed MPO Positivity (Case27). Fig 3B-AML M2Bone Marrow Smear
of a Patient Showing MPO Positivity (Case X1)
Fig-4A:
ALL:
(FAB–ALL L1) BM Picture of a 16 Yrs Male Shows Small, Uniform Blast Cells with
Scanty Cytoplasm and Mostly Single Nucleolus. MPO was Negative (Case40). Fig
4B- JCML: Peripheral Blood Smear of a 10 Yrs Boy Shows Occasional Blast Forms,
Atypical Agranular Bands And SegmentedNeutrophils (Case49).
Conclusion
Evaluation
of the causes of non-haemolyticanemia
seems to be important as the various causes would respond to different
treatment modalities; thus enabling the physician to plan out a successful
therapeutic outline that increase the patient’s longevity.
The investigation of a case of severe
non haemolyticanemia should include thorough clinical, haematological and
related specific investigations. The causes of anemia varies from place to
place depending on geographical variation, ethnicity, economy, food habits etc.
Authors’ contributions:
Rsasdhar
Deka designed, searched data and literature and gave a critical view of
manuscript writing. Prabir Hazarikagave critical view of manuscript writing.
Both the authors’ read and approved the final manuscript.
Acknowledgements: We
acknowledge the support provided by the head of the department and the
laboratory staffs of pathology department and also the clinician colleagues for
sending the cases to us.
Financial support and sponsorship: Nil.
Conflicts of Interest: There are no conflicts of interest.
References
How to cite this article?
Deka
R., Hazarika P. A clinicopathological study of severe non-haemolytic
anemia in age group of 0-18 years. Trop J Path Micro 2018;4(7):539-544.doi:10.17511/
jopm. 2018.i7.10.