A clinicopathological study of severe non-haemolytic anemia in age group of 0-18 years

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.


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. 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.

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%). 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. Majority of the cases had haemoglobin level between 5 to ‹ 7 gm/dl and 5 cases had haemoglobin level below 3gm/dl.
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].  [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].
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.
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.

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.