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ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 307-310  

Megaloblastic anemia - A clinical spectrum and a hematological profile: The day-to-day public health problem


Department of Pathology, Prathima Institute of Medical Sciences, Karimnagar, Hyderabad, Telangana, India

Date of Web Publication17-May-2016

Correspondence Address:
S Srikanth
Department of Pathology, Prathima Institute of Medical Sciences, Karimnagar, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.182497

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  Abstract 

Aims and Objectives: To know the various parameters and diagnostic approach of megaloblastic anemia. To know the age incidence and sex ratio. Materials and Methods: A hospital-based retrospective and prospective study was done for a period of 1-year. Totally, 21 cases were analyzed, and we correlated signs, symptoms, and hematological investigations. Results: Totally, 21 children with megaloblastic anemia in the above said period were studied. The patients age group was ranged from 2 months to 15 years. Megaloblastic anemia was observed in all the cases. Conclusion: Megaloblastic anemia is one of the common causes of undiagnosed anemia, and the treatment is simple and easily affordable. If left untreated, it can lead to morbidity both because of anemia and attendant neurological involvement.

Keywords: Megaloblastic anemia, neurological involvement, neutropenia


How to cite this article:
Srikanth S. Megaloblastic anemia - A clinical spectrum and a hematological profile: The day-to-day public health problem. Med J DY Patil Univ 2016;9:307-10

How to cite this URL:
Srikanth S. Megaloblastic anemia - A clinical spectrum and a hematological profile: The day-to-day public health problem. Med J DY Patil Univ [serial online] 2016 [cited 2021 Dec 3];9:307-10. Available from: https://www.mjdrdypu.org/text.asp?2016/9/3/307/182497


  Introduction Top


Megaloblastic anemias are a group of disorders characterized by the presence of distinctive morphological appearances of the developing red cells in the bone marrow. The cause is usually deficiency of either cobalamin or folate, but megaloblastic anemia may arise because of inherited or acquired abnormalities affecting the metabolism of these vitamins or because of defects in DNA synthesis not related to cobalamin or folate. Macrocytosis is found in 2.5-4% of adults who have a routine complete blood count. In up to 60% of cases, macrocytosis is not accompanied by anemia; however, isolated macrocytosis should always be investigated. Macrocytosis without anemia may be an indication of early folate or cobalamine deficiency, as macrocytosis preceded development of anemia. The average Indian vegetarian diet is deficient in cobalamine. [1]


  Materials and Methods Top


A hospital-based retrospective analysis of case records of all patients admitted and diagnosed as megaloblastic anemia was done. Those with a diagnosis of aplastic anemia were excluded from the study. The study period is for 1-year and all the patients admitted from the age group of 2 months to 15 years were included in the study. The data were collected, and multivariate analysis was done to determine the correlation between symptoms, signs, and hematological investigations.


  Results Top


Twenty-one children with megaloblastic anemia in the above said period were studied. There was a bimodal distribution with 66.6% of patients being between 2 months and 3 years and 33% being in the age group of 13-15 years. There were no patients in the age group of 3-13 years. Megaloblastic anemia was more common in female children with the ratio being 1.6:1 in favor of females. The most common symptoms were pallor, fatigue, and neurological involvement. The frequency of symptoms and signs are as listed in [Table 1] and [Table 2] respectively.
Table 1: Frequency of symptoms

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Table 2: Frequency of signs

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The number of patients who had severe anemia (hemoglobin <7 g%) was 14 (66.6%). Macrocytosis was found in 81% of peripheral smears [Figure 1] and bone marrow confirmed megaloblastic anemia in 92.99%. Bone marrow was performed using Salah's needle after giving 5 mL of 5% local anesthesia. All the marrows were performd on the iliac crest only. Vitamin B 12 assay that was done in eight patients showed low levels (<100 pg/mL). Resolution of anemia was seen with treatment in 10 patients who subsequently followed-up (47.6%). The mean time taken for resolution of anemia was 42.5 days. There was a resolution of the neurological signs, most importantly apathy in all the seven patients who had neurological signs.
Figure 1: Smear showing macrocytes along with few normocytes (Leishman, ×100)

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  Discussion Top


Megaloblastic anemia is a panmyelosis, even though its name suggests a disorder limited to red cells and erythroid hyperplasia is a prominent feature. Indeed, the immature appearance of megaloblastic nuclei and occasionally intense myeloid proliferation in the marrow has led to a misdiagnosis of leukemia in rare cases. The morphologic hallmark is nuclear-cytoplasmic dissociation, which is the best appreciated in precursor cells in the bone marrow aspirate.

There are various causes for the deficiency of both Vitamin B 12 and folate that include parasitic infections like Diphyllobothrium latum, alcoholism, vegetarianism, gastrectomy drugs like oral contraceptives and anticonvulsants. With achlorhydria and loss of pepsin secretion, Vitamin B 12 is not readily released from proteins in food. With gastrectomy and pernicious anemia, intrinsic factor is not available for transport to the ileum. The only dietary sources of Vitamin B 12 are foods of animal protein origin such as kidney, liver, heart, muscle meats, fish, eggs, cheese and milk. In contrast to folate, vegetables contain practically no Vitamin B 12 . Cooking has little effect on its activity. Vitamin B 12 is synthesized in the human large bowel by microorganisms but is not absorbed from this site and thus, the humans are entirely dependent upon dietary sources. Vegetarians are more prone for megaloblastic anemia as compared to that of nonvegetarians.

Megaloblastic nuclei are larger than normoblastic nuclei, and their chromatin appears abnormally dispersed due to its retarded condensation [Figure 2]. Giant band forms and metamyelocytes [Figure 3]a with unusually large and often mishappen nuclei along with mitotic activity are typically seen. Perl's stain was also done, and it was positive for iron [Figure 3]b.
Figure 2: Bone marrow aspiration smear showing megaloblasts with open sieve like chromatin and royal blue cytoplasm (Leishman, ×100)

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Figure 3: (a) Bone marrow aspiration smears showing megaloblasts, mitotic figures, and giant metamyelocytes (Leishman, ×100). (b) Smears showing positive for Perl's stain (Perl's, ×40)

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The common feature of all megaloblastic anemias is a defect in DNA synthesis that affects rapidly dividing cells in the bone marrow and other tissues. Many symptomless patients are detected through the finding of a raised mean corpuscular volume on a routine blood count. The main clinical feature in more severe cases is those of anemia. Anorexia is usually marked, and there may be weight loss, diarrhea or constipation. Other features include glossitis, angular cheilosis, a mild fever in the more severely anemic patients, unconjugated jaundice and reversible melanin skin hyperpigmentation. Thrombocytopenia sometimes may lead to bruising. The anemia and low leucocyte count may predispose to infections, particularly of the respiratory or urinary tracts.

Neutrophils with characteristic hypersegmented nuclei appear in the blood early in the course, but they do not arise directly from the giant metamyelocytes [Figure 4]. The mechanism of hypersegmentation and why it persists in the blood for more than a week after therapy are unknown. As megaloblastic anemia progresses, neutropenia and thrmocytopenia develop. These can be severe in advanced cases but are uncommon when anemia is mild. Some studies show that 40% of normal Indian subjects with normal hemograms were cobalamin deficient. [2]
Figure 4: Smear showing hypersegmented neutrophil and macro ovalocytes (Leishman, ×100)

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The onset of megaloblastic anemia is usually insidious with typical anemic symptoms of lethargy, weakness, and a yellow or waxy pallor. Dyspeptic symptoms are common. Glossitis with a beefy red tongue or more commonly a smooth pale tongue is characteristic. Loss of weight and loss of appetite are common complaints. Atrophy of the gastric parietal cells causes decreased secretion of intrinsic factor and hydrochloric acid. Bouts of diarrhea may be the result of epithelial changes in the gastrointestinal tract. In obstetric practice supplementation of iron and folate is the norm. Folate supplementation alone in the presence of occult cobalamin deficiency may precipitate neurological complications. [3]

Neurologic disturbances occur only in cobalamin deficiency, not in folic acid deficiency. These are the most serious and dangerous clinical signs because neurological damage may be permanent if the deficiency is not treated promptly. The bimodal nature of the disease can be due to the vulnerability of the age groups. The infants rely on the breast milk of the mother. A child breast fed by a mother who is a strict vegetarian has a higher risk of developing megaloblastic anemia. In the present study all the blood films were stained by the Leishman stain [4] and evaluated for red cell morphology, platelet count and white cell count by two hematologists. [Table 3] shows the various hematological profile.
Table 3: Hematological profile

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To conclude megaloblastic anemia is one of the common causes of undiagnosed anemia, and the treatment is simple and easily affordable. If left untreated, it can lead to morbidity both because of anemia and attendant neurological involvement. The commonest manifestations in megaloblastic anemia include triad of pallor, hyperpigmented skin, and neurological involvement. Neutropenia is a common concomitant finding in megaloblastic anemia and can be associated with leucopenia in a small number of patients. A correct diagnosis and prompt therapy lead to a complete and an eventful recovery.

 
  References Top

1.
Antony AC. Vegetarianism and vitamin B-12 (cobalamin) deficiency. Am J Clin Nutr 2003;78:3-6.  Back to cited text no. 1
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2.
Khanduri U, Sharma A, Joshi A. Occult cobalamin and folate deficiency in Indians. Natl Med J India 2005;18:182-3.  Back to cited text no. 2
    
3.
Antony AC. Megaloblastic anemia. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, et al., editors. Hematology. Basic Principles and Practice. 4 th ed. Edinburgh: Churchill Livingstone; 2005. p. 519-56.  Back to cited text no. 3
    
4.
Bain BJ, Lewis SM. Preparation and staining methods for blood and bone marrowfilms. In: Lewis SM, Bain BJ, Bates I, editors. Practical Haematology by Dacie and Lewis. 9 th ed. Edinburgh: Churchill Livingstone; 2001. p. 47-64.  Back to cited text no. 4
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]


This article has been cited by
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[Pubmed] | [DOI]



 

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