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REVIEW ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 63-66

Megaloblastic anemia: An updated review


NIMS College of Paramedical Technology, NIMS University, Jaipur, Rajasthan, India

Date of Submission23-May-2022
Date of Decision16-Aug-2022
Date of Acceptance29-Aug-2022
Date of Web Publication16-Nov-2022

Correspondence Address:
Atul Khajuria
Medical Laboratory Technology, NIMS College of Paramedical Technology, NIMS University, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/DYPJ.DYPJ_40_22

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  Abstract 

Megaloblastic anemia is a kind of anemia, which is triggered by means of inhibition of DNA synthesis at some point of erythropoiesis. The most frequent motive of defects in red blood cell DNA synthesis is vitamin deficiency, especially vitamin B12 deficiency or folic acid deficiency. Micronutrient loss can additionally be a cause. Moderate deficiency can consist of swollen tongue and neurological problems, inclusive of peculiar sensations such as a tingling sensation, whereas severe deficiency can encompass reduced coronary heart feature and greater serious neurological issues

Keywords: Folic acid deficiency, megaloblastic anemia, pernicious anemia, treatment, vitamin B12 deficiency


How to cite this article:
Khajuria A, Sehrawat R. Megaloblastic anemia: An updated review. D Y Patil J Health Sci 2022;10:63-6

How to cite this URL:
Khajuria A, Sehrawat R. Megaloblastic anemia: An updated review. D Y Patil J Health Sci [serial online] 2022 [cited 2022 Nov 27];10:63-6. Available from: http://www.dypatiljhs.com/text.asp?2022/10/2/63/361368




  Introduction Top


Macrocytic anemias are characterized with the aid of giant red cells with a diameter of greater than 9μ and a mean corpuscular quantity of >100 fL. The motives of macrocytic anemias may also be broadly divided into megaloblastic and non-megaloblastic relying on the look of developing red cell precursors in the bone marrow megaloblastic anemias can be classified into two main categories. The foremost divisions are vitamin B12 (cobalamin, Cbl) deficiency and folic-acid deficiency. The time period megaloblastic refers to the abnormal marrow erythrocyte precursor viewed in processes, such as pernicious anemia, related to altered DNA synthesis. Macrocytes can show up in the absence of a megaloblastic process. For example, an expanded mean corpuscular volume (MCV) can result actually from enlargement in the wide variety of circulating reticulocytes, which are larger than mature erythrocytes. The most frequent motives of megaloblastic anemia are acquired, although congenital types exist. Deficiencies in cobalamin, folate, or each account for the majority of cases. The most frequent disease of cobalamin deficiency is pernicious anemia. Less-frequent manifestations can manifest as the end result of a gastrectomy, inflammatory problems of the terminal ileum, or infestation with fish tapeworm Diphyllobothrium latum. Folic-acid deficiency is normally brought on by inadequate dietary intake.[1]

Red blood cells (RBCs) in megaloblastic anemias have an atypical nuclear maturation and an imbalance between nuclear and cytoplasmic maturation. The absence of vitamin B12 or folates impairs DNA synthesis, which slows nuclear replication and delays every step of maturation. The premitotic interval is prolonged. These effects in a giant nucleus increased cytoplasmic RNA and early synthesis of hemoglobin. Many cells in no way endure mitosis and breakdown in the bone marrow, producing extraordinarily multiplied stages of serum lactic dehydrogenase. This deficiency can impair maturation in myelogenous white blood cells and megakaryocytes, producing leukopenia with neutrophilic hypersegmentation and thrombocytopenia. Megakaryocyte fragments and large platelets may additionally be considered on peripheral blood smears. Megaloblastic anemias such as pernicious anemia are additionally characterized by energetic intramedullary hemolysis.


  Etiology Top


Megaloblastic anemia prompted via diet B12 deficiency is associated with

  • Increased utilization of vitamin B12 due to the fact of parasitic infections such as D. latum (tapeworm) and pathogenic bacteria in issues such as diverticulitis and small bowel structure.


  • Malabsorption syndrome brought on by means of gastric resection, gastric carcinoma, and some varieties of celiac disorder or sprue.


  • Nutritional deficiency or diminished furnish of vitamin B12. Cobalamin is synthesized by way of microorganism and is found in soil and contaminated water. Foods of animal origin (e.g., meat, eggs, and milk) are the fundamental dietary sources. The quantity of cobalamin in the common Western diet (5–15 mg/day) is extra than sufficient to meet normal requirements. The body can save giant quantities of cobalamin. Because of this, it can take 2–5 years for a deficiency to improve even in the presence of extreme malabsorption.


  • Chronic atrophic gastritis can occur due to the deficiency of pernicious anemia as well as megaloblastic anemia.


  • Abnormal absorption prompted by means of celiac disorder or sprue.


  • Increased utilization brought on by way of being pregnant or some acute leukemias.


  • Treatment with ant metabolites that act as folic acid antagonists.



  •   Epidemiology Top


    Epidemiological research on megaloblastic anemia in Nigeria and in Africa is sparse. However, the frequency of megaloblastosis is best possible in nations in which malnutrition is rampant and events vitamin supplementation for aged people and pregnant women is no longer available. Faulty preparations of meals and extended demand for folate in the course of pregnancy are the most frequent reasons for megaloblastic anemias.

    Approximately 1 in 7,500 humans develops pernicious anemia in the USA per year; however, this has been modified by modern-day fortification of meals and diet vitamins in aged sufferers in the USA. International records confirmed that pernicious anemia and folate deficiency typically occur in persons older than 40 years and the occurrence will increase with older populations. The incidence of pernicious anemia is stated to be greater in Sweden, Denmark, and United Kingdom than in different developed international locations.[2] Research studies have currently documented that 1.9% of persons older than 60 years have undiagnosed pernicious anemia. Earlier research advised that pernicious anemia is restricted to Northern Europeans; however, more recent studies report the disorder in each Blacks and Latin Americans. The median age at analysis is 60 years. A slightly greater number of women than men are affected.


      Physiology Top


    Normal red cell maturation is based on many hematological factors; two of which are the vitamin B12 coenzymes (also known as cobalamin) and folates. Megaloblastic dyspoiesis occurs when one of these elements is absent. Vitamin B12 and a range of structurally comparable compounds, known as cobalamin analogs, that lack the functional coenzyme recreation of the vitamin appear in nature as a product of sure microorganisms. It will become available to people via the meals chain. Approximately one-third of the body’s common whole of 5,000 mg is saved in the liver. The average loss of nutrition B12 is approximately 5 mg/day. An adult requires approximately 5 mg of diet B12 per day to balance this loss, with an increased need for the duration of uncommon intervals such as pregnancy. An everyday food regimen carries 5–30 mg. Folates are ample in yeast, many leafy vegetables, and organ meats such as liver and kidneys. The human body stores little folic acid. Storage quantities would final approximately 3–4 months if an entire absence of dietary folates existed. However, a chronically insufficient eating regimen can produce folic acid deficiency anemia. In addition to a negative diet, alcohol is the most frequent pharmacological motive of folic-acid deficiency. However, folic-acid antagonists, such as positive drugs used to deal with leukemias and oral contraceptives, show up to reduce the absorption of folic acid.


      Pathophysiology Top


    The two vitamins, that is, folate and cobalamin, act synergistically in producing the thymidylic acid used for DNA synthesis. Therefore, in cobalamin deficiency, the megaloblastic arrest is actually brought on by means of a deficit in folate utilization. As shown in [Figure 1] (activated methyl cycle), methionine is generated by means of switch of methylene team from N5-methyl tetrahydrofolate (FH4) to homocysteine the use of the enzyme methyl transferase (Methionine synthase). In this biochemical process, methylcobalamin is the element that assists in methyl transfer as coenzyme form of cobalamin. This is why the morphological abnormalities emanating from either cobalamin or folate deficiency show up precisely alike.
    Figure 1: Role of vitamin B12 as a enzyme in megaloblastic anemia

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      Clinical Features Top


    Megaloblastic anemias, irrespective of the cause, share sure widely widespread features. The anemia develops slowly with little or no signs and symptoms till the hematocrit is severely depressed and at this point, signs such as weakness, palpitation, fatigue, mild headedness, and shortness of breath occur. Severe pallor and mild jaundice mix to produce a telltale lemon yellow skin. Slight variations appear in clinical signs and symptoms of megaloblastic anemia depending on whether or not it is prompted by using folate deficiency or by means of vitamin B12 deficiency. In folate deficiency, fundamental clinical aspects consist of anemic syndrome, pallor, icterus, hunter’s syndrome, nail pigmentation, alternate of hair shade (early graying), and splenomegaly in approximately 10%–15% of patients. In addition to the aforementioned features, cobalamin deficiency manifests with neurological symptoms, which encompass loss of joint role feel in the second toes, loss of vibration experience in toes and fingers, paraesthesia, hypoesthesia, tingling sensation, gait abnormalities, loss of coordination, muscle weakness, spasticity, optic neuropathy, urinary and fecal incontinence, erectile dysfunction, dementia, and reminiscence loss. These neuropathies are symmetric and solely have an effect on decreased extremities. Demonstrable signs include fine Romberg’s sign, Babinsky reflex, Lhermitte’s sign, spasticity, hyporeflexia, and clonus.


      Laboratory Diagnosis Top


    Pernicious anemia, the most frequent megaloblastic anemia, is a prototype of the complete group. The hematological picture is the identical whether or not the motive is diet B12 or folic acid deficiency. However, assisting laboratory assays will vary for a number megaloblastic anemias. The hemoglobin and red cell counts are generally extremely low in this anemia. However, the microhematocrit (packed cell volume) can also no longer reflect the real minimize in erythrocytes because of the enlarged dimension of the pink cells. This increase in red cell measurement is usually reflected in the suggested corpuscular volume (MCV), which may also be as excessive as 130 fL. The mean corpuscular hemoglobin (MCH) usually varies in approximately 90% of cases. Concurrent conditions that limit the MCV, such as thalassemia or iron deficiency, may reason the MCV to be normal. The imply corpuscular hemoglobin attention (MCHC) is commonly normal. In this anemia, platelet counts are normally somewhat decreased. The complete white blood cell count number will classically show a leukopenia, especially a neutropenia.[1] Examination of a peripheral blood smear exhibits a moderate-to-significant anisocytosis and poikilocytosis with many macrocytic, ovalocytic red cells. Erythroid precursors, incredibly metarubricytes, may additionally be observed. Red cell inclusions such as basophilic stippling, Howell–Jolly bodies, and Cabot rings might also be observed. Abnormalities in leukocytes may additionally consist of hypersegmented (more than four lobes) neutrophils and an extension in the percentage of eosinophils (eosinophilia). The number of platelets are also reduced. The reticulocyte count is much less than 1% in untreated pernicious anemia and is low for the degree of anemia. However, subsequent to nutrition B12 treatment, assuming that the patients no longer have antibodies toward interferon (IFN), the reticulocyte count can amplify up to 25% in 5–8 days.

    Pancytopenia may also be considered in superior cases. In severe anemia with a hematocrit of much less than 20%, promegaloblasts and nucleated erythrocytes might also be seen, precipitated by extramedullary hematopoiesis in the spleen and very early marrow release. A dimorphic population of red cells might also be present with concurrent iron deficiency. The red cell distribution width is high. The bone marrow is normally hypercellular with megaloblastic modifications in both the erythroid line or all lines; however, it can be hypocellular and mimic aplastic anemia.[3]

    Erythrocyte precursors are enlarged with a reduced nuclear-cytoplasmic ratio. Nuclear-cytoplasmic asynchrony, with the relative immaturity of the nucleoplasm, is typical. Changes give red cells a dysplastic appearance, and a wrong diagnosis of myelodysplastic syndrome can be made. Granulocytic precursors can also additionally show nuclear-cytoplasmic dissociation and enlargement. Characteristically, massive metamyelocytes with large, incompletely segmented nuclei are seen.


      Treatment Top


    The trendy cure for nutrition B12 deficiency is regular monthly intramuscular injections of at least a 100 mg of vitamin B12 to right the diet deficiency. This regimen corrects the anemia and may additionally right the neurological complications if administered quickly after the onset of symptoms. A similar advice is that aged sufferers with gastric atrophy must take capsules containing 25–1 mg of vitamin B12 each day to forestall vitamin B12 deficiency. This recommendation supposes that approximately 1% of vitamin B12 is absorbed by using mass motion in the absence of IF. A profitable response to therapy with cobalamin (vitamin B12) or folate starts within 8–12 h in the bone marrow, with a decision of megaloblastic hematopoiesis. The reticulocyte count starts to increase 2–3 days after therapy and peaks in 5–8 days; greater and later peaks happen in extra severe anemia. The hematocrit starts to increase in approximately 1 week and will normalize within 4–8 weeks. The MCV typically increases for the first 3–4 days, most likely due to the fact of reticulocytosis, and then starts to decrease. The regular reference range is predicted to be reached in 25–78 days. Resolution of neurological abnormalities is structured on the length of loss. Most neurological signs will exhibit maximal improvement within 6 months of initiation of therapy. Serum iron levels will start to fall within 24 h of profitable treatment, but the affected person ought to be located over the subsequent 2–3 weeks.[2]


      Conclusion Top


    Megaloblastic anemia is a kind of anemia induced by the inhibition of DNA synthesis during erythropoiesis. The most frequent motive of defects in RBC DNA synthesis is vitamin deficiency, mainly vitamin B12 or folic acid deficiency. On average deficiency, tongue inflammation and neurological issues may begin. Megaloblastic anemias are characterized by impaired DNA synthesis and wonderful RBC precursors megaloblasts in the bone marrow and macrocytic red cells in the peripheral blood. The megaloblasts are large, ordinary precursors of RBCs, which exhibit nuclear-cytoplasmic asynchrony.

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    Conflicts of interest

    There are no conflicts of interest.



     
      References Top

    1.
    Turgeon ML Megaloblastic anemias. In: Clinical Hematology: Theory and Procedures. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. p. 181.  Back to cited text no. 1
        
    2.
    Chanarin I The Megaloblastic Anaemias. 2nd ed. Oxford, England: Blackwell Scientific Publishers; 1979.  Back to cited text no. 2
        
    3.
    McClatchey KD Clinical Laboratory Medicine. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.  Back to cited text no. 3
        


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      In this article
       Abstract
      Introduction
      Etiology
      Epidemiology
      Physiology
      Pathophysiology
      Clinical Features
      Laboratory Diagnosis
      Treatment
      Conclusion
       References
       Article Figures

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