Introduction: Adolescence is a vulnerable period for development of anemia. Anemia in adolescence has serious implications for a wide range of outcomes. It causes reduced resistance to infection, impaired physical growth and mental development, reduced physical fitness, work capacity and school performance. Objectives: The aim of the present study was to study the clinical profile of the adolescents (10-18 years) admitted with severe anemia. Methods: A hospital based retrospective study was conducted in the Department of Pediatrics, Dr Rajendra Prasad Government Medical College Kangra, a tertiary care institute in North India, during the period from January 2015 to December 2016. The participants in our study were the adolescent patients (10-18 years) admitted with primary diagnosis of severe anemia (Hemoglobin <7gm %). The diagnosis of type of anemia was based on hematological indices and red cell morphology on peripheral smear. Results: There were 39 patients admitted with severe anemia. This constituted 1.90% of all the admissions during the study period. The mean age of the patients was 14.97 (± 1.86) years and the mean hemoglobin was 4.66 (± 1.28) gm%. There was a female preponderance with 66.67% females as against 33.33% males. Megaloblastic anemia was the most common type of anemia (52.28%) followed by iron deficiency anemia (30.77%) and dimorphic anemia (15.38%). All of the patients belonged to poor socioeconomic status and most of them (89.74%) were vegetarian. Conclusion: Although iron deficiency anemia is the most common type of anemia in India, yet in adolescents megaloblastic and dimorphic anemia should be looked for whenever the adolescents present with severe anemia especially in the setting of malnutrition and dietary inadequacy.

Erythrocyte membranes obtained from patients with severe megaloblastic anemia contain spectrin as indicated by double immunodiffusion against anti-spectrin raised in rabbits. These membranes have normal protein patterns determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate after solubilization at 100 degrees C for 3 min in SDS. When incubation is carried out at 37 degrees C for 3 hours, however, the membrane protein patterns become grossly abnormal, lacking spectrin, band 3 and having several diffuse smaller bands. Cross-linking of these membranes with SH oxidizing agents, such as diamide prevented this dissociation phenomenon. The SH group content of megaloblastic membranes, both from severe and mild megaloblastic anemia, was significantly higher than that of control membranes. This was also confirmed by the greater incorporation of 3H-N-ethylmalemide into red cell membranes from mild and severe megaloblastic anemia than controls. Incorporation of this probe was greatest into the band 3 region. These findings indicate that the erythrocyte membrane proteins in megaloblastic anemia have an intrinsic abnormality which renders them more susceptible to degradation by their endogenous proteases.

Anemia is a common complication in malarial infection. Direct destruction and ineffective erythropoesis does not adequately explain the cause of anemia in malaria. We present a case with refractory megaloblastic anemia with asymptomatic falciparum malaria. We hypothesize that promoter variants in the inducible nitric oxide synthase gene might be the cause of severe refractory megaloblastic anemia and pancytopenia in our patient. Malaria should always be kept in mind as a cause of anemia especially in endemic areas even if the child is asymptomatic or there is no demonstrable parasite on routine smear examination.

Macrocytic anemia is usually associated with vitamin B12 or folate deficiency. However, folate deficiency was rarely reported as a cause of hemolytic anemia. We present a case of a young man with a history of alcohol abuse who initially presented with an acute on chronic abdominal pain and was found to have jaundice and scleral icterus. His liver enzymes were unremarkable, and his abdominal imaging did not reveal any acute pathology. However, he was found to have a severe non-immune hemolytic anemia secondary to folate deficiency.

Anemia during pregnancy is defined as a serum hemoglobin of less than 10.5 g/dL in the second trimester of pregnancy, and it is defined as a serum hemoglobin of less than 11 g/dL in the third trimester of pregnancy. There is evidence that maternal anemia raises the likelihood of health issues occurring in both the mother and the child. The anemia known as megaloblastic anemia is characterized by macrocytosis as a consequence of the reduction of DNA synthesis while erythropoiesis is taking place. This results in an increased number of red blood cells. The presence of megaloblastic anemia is often identified by chance during the course of routine blood testing. The only persons who have symptoms of anemia during pregnancy are those who already have a severe level of anemia. If treatment for megaloblastic anemia is not received, the condition may lead to thrombocytopenia. The first step in diagnosing megaloblastic anemia is identifying the morphological (increased mean cellular volume) and laboratory (specific vitamin deficiency) symptoms of megaloblastosis. This will lead to the identification of megaloblastic anemia. We take a look at the situation of a woman in her thirties who is expecting a child but has been told she has significant megaloblastic anemia and thrombocytopenia.

Anemia is common during adolescence. However, severe anemia is uncommon and can have varied etiology. This study was conducted to find out the profile of adolescents (10–18 years) admitted for severe anemia. The Case records of children between 10 and 18 years old admitted during the year 2008 in Kalawati Saran Children’s Hospital for severe anemia as admitting diagnosis were reviewed. There were 40 patients admitted with severe anemia during the year 2008. This constituted 3.37% of all the admissions. Mean age of these patients was 12 (+/−2.5) years and mean hemoglobin at admission was 3.6 (+/−1.4) g%. Megaloblastic anemia was most common type of anemia (42.5%) followed by aplastic anemia (27.5%) and 15% cases were due to severe iron deficiency anemia. Although iron deficiency anemia is the most common type of anemia, but in adolescents megaloblastic anemia and aplastic anemia should be looked for whenever the adolescents present with severe anemia.

Several medications have been linked to red blood cell (RBC) disorders. The frequency of these side effects varies, depending on the condition, but they can be associated with significant morbidity and mortality. The problem is likely to exacerbate in aging populations with frequent comorbidities, proportional to the growing number of medications used. Notable drug-related RBC disorders include hemolytic anemia, megaloblastic anemia, sideroblastic anemia, polycythemia, methemoglobinemia, anemia of irritation/inflammation, and anemia caused by suppression of RBC production. The list of medications that are associated with these disorders is long and includes many commonly-used drugs. This could pose a challenge in timely diagnosis and management of these disorders. Prior knowledge of the potential for drug-related RBC disorders and monitoring the patients who are being treated with medications known to cause RBC disorders are critical to ensure timely and effective response, should such adverse reactions occur.

MANY DRUGS can cause intense hemolysis when administered to individuals whose red blood cells (RBC) are deficient in glucose-6-phosphate dehydrogenase (G-6-PD).¹One of these, nitrofurantoin (Furadantin) has also been suspected on at least two occasions of being etiologically associated with the development of megaloblastic anemia.^2,3In the case described below, severe anemia with both intense hemolysis and megaloblastic erythropoiesis promptly followed the ingestion of nitrofurantoin by a previously nonanemic pregnant Negro woman. The anemia was rapidly corrected when the nitrofurantoin therapy was stopped and folic acid was administered. Report of a Case A 22-year-old Negro woman, pregnant for the fourth time, was first seen during this pregnancy in Prenatal Clinic on Aug 18, 1964, when about 27 weeks pregnant. During her third pregnancy two years before, numerous blood studies had been carried out as part of an extensive survey of the maternal hematologic changes associated with twinning. She

Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B₉) deficiency and cobalamin (vitamin B₁₂) deficiency. Megaloblastic anemia can be diagnosed based on characteristic morphologic and laboratory findings. However, other benign and neoplastic diseases need to be considered, particularly in severe cases. Therapy involves treating the underlying cause—eg, with vitamin supplementation in cases of deficiency, or with discontinuation of a suspected medication.

1. The effect of the administration of choline chloride has been observed in 10 cases of megaloblastic anemia of various types. 2. Choline was without effect in a case of untreated Addisonian pernicious anemia which subsequently responded to parenteral liver therapy. 3. Choline was also without effect in a case of nutritional megaloblastic anemia, in a case of megaloblastic anemia of pregnancy, and in two cases of megaloblastic anemia associated with the sprue syndrome. All these cases had proved refractory to injections of potent liver extract before the choline was given, and all responded to subsequent oral liver or folic acid therapy. 4. A significant erythropoietic response to choline occurred in two cases resembling Addisonian pernicious anemia which were refractory to parenteral liver extracts. Secondary responses followed the administration of choline in two other cases of Addisonian pernicious anemia and in a case of megaloblastic anemia of pregnancy, all of which had already responded to injections of liver extract. 5. The significance of these observations is discussed. It is concluded that choline possesses no direct erythropoietic activity, but that under certain circumstances it may potentiate the effect of liver extracts. It is suggested that refractory megaloblastic anemias may be divided into two groups. In one, represented by well known syndromes associated with defective absorption or pregnancy, the lack of response to parenteral liver extracts is not corrected by choline. In the other, represented by two cases simulating Addisonian pernicious anemia, choline is effective in overcoming, partially or completely, the refractoriness to parenteral liver therapy. Consideration is given to the view that the refractoriness of this group results from hepatic dysfunction. 6. The most satisfactory method of administering choline probably consists of intravenous injections in daily doses of 1 gram. Larger doses given intravenously are frequently accompanied by unpleasant side effects, while oral administration appears to be relatively less effective. 7. It seems unlikely that choline will be of practical value in the treatment of refractory megaloblastic anemias, for which oral liver preparations provide the most certain and effective treatment. It is possible, however, that choline may be of use in cases complicated by severe hepatic disease.

The case of a 15-month-old, strictly breast-fed infant whose mother had been following a vegetarian diet for ten years is reported. The infant had severe megaloblastic anemia with an arrest in growth, hypotonia, and failure of psychomotor development. The very low levels of vitamin B12 in the infant's serum and mother's milk confirmed the diagnosis. Management of such cases consists in administration of vitamin B12 supplements, with a blood transfusion if needed. Other concomitant deficiencies should be looked for. The outcome is rapidly favorable. The patient reported here is now four years of age and has normal statural growth and psychomotor development.

We report the case of a 7-month-old breast fed infant who presented with a nose bleed and bruises. Investigation showed severe nutritional B12 deficiency anemia with a pancytopenia. It is important to take the nutritional history of both the infant and the mother for early prevention and treatment.

The case of a patient who developed megaloblastic anemia caused by folate deficiency during treatment with primidone is reported. The serum level of folic acid was significantly low. Two causes able to produce folate deficiency have been discovered: chronic assumption of primidone, and low dietary intake of folic acid. The anemia was completely reversed by oral supplementation of folic acid. It has already been recognized that additional nutritional deficiency is required to precipitate a frank megaloblastic anemia during therapy with antiepileptic drugs.

The erythrocyte membrane protein pattern of patients with megaloblastic anemia was determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. In severe megaloblastic anemia, secondary either to folic acid or vitamin B12 deficiency, the erythrocyte membrane protein pattern was grossly abnormal, lacking bands 1, 2 (spectrin), and 3 and having several diffuse, faster migrating bands. After adequate vitamin replacement therapy, the erythrocyte membrane protein pattern returned to normal. In mild megaloblastic anemia, secondary either to folic acid of vitamin B12 deficiency, and in severe iron deficiency anemia, the erythrocyte membrane protein pattern was normal. Erythrocyte membrane protein pattern of normal membranes did not change after mixing with abnormal membranes before polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Protease activity extracted from membranes of megalocytes was not different from normal. These findings indicate that the erythrocyte membrane protein pattern is abnormal in severe megaloblastic anemia and that this abnormality is not secondary to increased activity of the endogenous erythrocyte membrane proteinase.

Background: Anemia is a major nutritional problem worldwide especially in developing countries. This research was conducted to find the incidence of severe anemia, to identify the common clinical features and etiology of it and to assess the requirement of packed red cell transfusion. Methods: All patients having severe anemia (hemoglobin <7 gm/dl in 6-59 months and <8 gm/dl in 5-14 years as per WHO definition) between 6-14 years were included in this study. Detailed medical history, anthropometric measurements and clinical examination were done. Complete blood count, peripheral smear, reticulocyte count and stool microscopy were done in all patients. Then anemia classified morphologically into microcytic, normocytic, macrocytic and dimorphic. Further investigations were done according to the peripheral smear to identify the etiology of severe anemia. Results: During the study period, 84 patients of severe anemia were hospitalized with incidence of 2.57%. It was more common in male in 6 months to 5 years and in female in 10-14 years age. 67% patients had microcytic, 28% had dimorphic and 2.5% each had normocytic and macrocytic anemia. The most common anemia was iron deficiency (82%) followed by anemia of chronic disease (17%), hemolytic anemia (12%), megaloblastic anemia (7%) and blood loss anemia (1%). Packed red cell transfusion was required in 16 (19%) patients with severe anemia. Conclusions: Good clinical examination with peripheral smear is helpful in classifying the anemia morphologically. Following this, the use of investigations as per the standard flow charts, helps in identification of etiology.

Severe megaloblastic anemia with a normal white blood cell and platelet count developed in a patient with psoriasis vulgaris who was receiving long-term, low-dose methotrexate. We believe she had methotrexate-induced folate deficiency anemia with isolated inhibition of the erythrocytic bone marrow line. We review hematologic toxicity from low-dose methotrexate. Physicians caring for patients who receive low-dose methotrexate should be aware that an increase in the erythrocyte mean corpuscular volume may be a useful indicator of folate deficiency and impending toxicity. In addition, folate supplementation may prevent this toxicity (even in patients who do not appear clinically to be folate deficient), although whether methotrexate efficacy diminishes is controversial.

The case of a young girl, born to a woman who was a vegetarian for 18 years, is presented. She had been exclusively breast-fed until the age of 6 months when a severe anemia was discovered with an extremely low hemoglobin level (1.9 g/100 ml). Her physical growth and psychomotor development had been normal until 3 months of age. Bone marrow showed megaloblastosis and the serum B12 level was low (45 ng/l). B12 levels were also decreased in both parents (110 and 105 ng/l) and in the mother's milk (12 ng/l). Treatment with parenteral B12 was successful. The importance of a careful dietetic inquiry in the case of an infant with megaloblastic anemia is stressed and likewise, as a preventive measure during all normal pregnancies.

We report a case of severe vitamin B-12 deficiency in a child who had a clinical presentation of hemolysis and thrombocytopenia that suggested the diagnosis of thrombotic thrombocytopenic purpura (TTP) and was associated with decreased ADAMTS13 activity. In this report, we review vitamin B-12 deficiency in children, the relationship between ADAMTS13 activity and TTP and discuss other conditions associated with decreased ADAMTS13 activity.

Vitamin B12 deficiency anaemia in adults is usually caused by Addison- Biermer's disease. The presence of antibodies against gastric parietal cells and intrinsic factor (IF) in blood is typical for the disease. The gastrointestinal malabsorption or a diet poor in vitamin B12 are rarer causes. The disease manifests in hematological, neurological, psychiatric disorders and trophic changes of the tongue and oral mucosa, which leads to weight loss. The authors describe a case of a 70-year-old woman with severe vitamin B12 deficiency based on chronic inflammatory lesions of the gastric mucosa caused by Helicobacter pylori infection. The patient had haematological (pancytopenia), neurological (problems with memory, concentration, numbness of the limbs, gait instability) and gastrological disorders (loss of appetite, weight loss). The laboratory and imaging diagnostics were performed. The neoplasmatic background was abandoned and pure vitamin B12 deficiency was diagnosed. All symptoms resolved completely after the supplementation and eradication of Helicobacter pylori. The article demonstrates the problem of many severe, non- specific complications of vitamin B12 deficiency which requires extensive diagnostics and treatment. The similarity of symptoms may suggest a malignant disease especially in elderly patients.

We report the case of an alcoholic patient with severe pancytopenia with low plasma folate level but normal erythrocyte folates and cobalamin levels. The bone marrow smear concluded to a pancytopenia due to folates and/or cobalamin deficiency. Severe pancytopenia due to acute plasma folate deficiency can be observed despite normal erythrocyte folates level which reflects the organism's folates store.

A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

Case report of a young woman, aged 27, suffering from severe megaloblastic anemia due to folic acid deficiency. The factor responsible for this deficiency seems to be the regular use of oral contraceptives for 3 years (Noracycline 22®). Recent investigation evidenced the existence of selective malabsorption of food folates, due to the action of hormonal contraceptives on the intestinal conjugase. It can thus be admitted that contraceptive drugs play a prominent part in the genesis of this type of anemia. However, other factors must also be considered, like malnutrition and a masked malabsorption syndrome. The relation with megaloblastic anemia in pregnancy is discussed

Background: Vitamin B₁₂ (cobalamin, cbl) deficiency in children is rare and may occurs in exclusively breast fed infants of mothers on vegetarian or vegan diet with lack of appropriate supplementation. The clinical manifestation of vitamin B12 deficiency include neurological disorders, megaloblastic anemia and failure to thrive. Routine and commonly used laboratory tests such as cell blood count (CBC) or serum vitamin B₁₂ level are sufficient for appropriate diagnosis. Typical therapy is based on intramuscular cobalamin injections. Early diagnosis and early onset of treatment are crucial factors for long-term prognosis of patients as the duration of deficiency may be correlated with the development of long lasting changes in the nervous system. The purpose of this article is to present influence of maternal vitamin B₁₂ deficiency as a cause of infant psychomotor retardation. Case presentation: We report the case of a 7 months old girl whose parents sought medical advice due to pathological somnolence and developmental regression of their daughter with onset approximately 2 months prior to the visit. Following several diagnostic tests it was determined that the infant’s symptoms were due to vitamin B₁₂ deficiency which was secondary to the mother’s latent Addison-Biermer disease. Apart from neurological symptoms the infant also showed megaloblastic anemia which is typical to cobalamin deficiencies. Intramuscular vitamin B₁₂ supplementation resulted in instant improvement of the patient’s general condition and blood morphology. Unfortunately, psychological examination indicated long-term psychomotor retardation due to delayed diagnosis of B₁₂ deficiency. Conclusions: Vitamin B₁₂ levels should be considered during differential diagnosis of neurological symptoms in exclusively breast-fed infants especially if they co-exist with megaloblastic anemia and psychomotor retardation.

The commonest etiologies of new-onset pancytopenia are congenital bone marrow failure syndromes, marrow space-occupying lesions, infections, and peripheral destruction. Nutritional deficiencies, including folate and vitamin B12, can occasionally cause pancytopenia. We report a 48-year-old gentleman who presented with a 1-week history of dizziness and upper gastrointestinal bleeding. Laboratory evaluation revealed pancytopenia, macrocytosis, toxic neutrophils, hemolysis, suppressed reticulocyte count, positive direct anti-globulin test (DAT), severely reduced B12 levels, and positive anti-intrinsic factor and anti-parietal cell antibodies. He was started on weekly intramuscular B12 supplementation and showed improvement in blood cell counts during follow-up. Recognition of B12 deficiency as a cause of pancytopenia and DAT-positive autoimmune hemolytic anemia can help to avoid unwanted investigations and aid in early diagnosis and treatment.

This excerpt has been provided in the absence of an Macrocytic megaloblastic anemias occur because of single or combined deficiencies of folic acid, vitamin B12, or ascorbic acid. Many other situations can result in mild or moderate macrocytosis, such as chronic liver disease, hemolytic anemia, refractory anemia (chronic bone marrow failure), but none of these produce a true megaloblastic bone marrow picture.Chemical, microbiologic, and isotopic studies of patients with macrocytic megaloblastic anemia indicate that several deficiencies usually are responsible. Even the patient with a Shilling test typical of pernicious anemia, which is due to vitamin B12 deficiency, often is deficient in folic acid and has a very low ascorbic...

Megaloblastic anemias are a group of hematologic disorders in which abnormal DNA synthesis causes blood and bone marrow disorders. This type of anemias occurs as a result of folic acid deficiency or impaired vitamin B12 absorption. The prevalence of this type of anemia is highly variable worldwide and megaloblastic anemia caused by lack of vitamin B12 (cyanocobalamin) is rare during pregnancy [1]. In this case report, we report follow-ups conducted for a pregnant 33-year-old woman, G2, P1, with a history of previous natural childbirth who attended Kamali Hospital due to labor pain associated with severe thrombocytopenia. Although this woman was injected 10 units of PLT and also vitamin B12 (cyanocobalamin), folic acid and corticosteroids in the course of treatment, her platelet level has not yet returned to normal levels after 6 months and she is still being treated.

To assess whether addition of cobalamin (cbl) to iron-folic acid will result in improved response in nutritional anemia. This study included 150 children aged between 0.5–5 y having nutritional anemia. Anemia was categorized for severity and red cell morphology. Serum levels of ferritin were obtained in all cases while levels of cbl and folic acid (FA) were done only in children having macrocytic or dimorphic anemia. Children were randomized to receive either iron and FA (Group I) or iron, FA and cbl (Group II). Response to treatment was assessed at 2, 4 and 8 wk. Of all the 150 patients, iron deficiency was documented in 111 patients. Of the 41 cases in whom, Cbl and FA levels were done, 97.56% and 53.66% had deficiency of cbl and FA respectively. Patients in group II had higher Hb level at 2, 4 and 8 wk (significant at 4 and 8 wk). Percentage Hb rise from baseline Hb was significantly higher in group II (p 0.00). In group II, increase in Hb among cases with macrocytosis and others were similar although percentage increase in Hb was more pronounced among patients with macrocytic anemia or dimorphic anemia. However, this difference was statistically not significant (p = 0.18). Children receiving cbl in addition to iron and FA showed an improved hematological response.

We describe 2 children with cobalamin G disease, a disorder of vitamin B metabolism with normal serum B levels. They presented with megaloblastic anemia progressing rapidly to severe thrombotic microangiopathy. In infants presenting with acute thrombotic microangiopathy, cobalamin disorders should be considered early as diagnosis and targeted treatment can be lifesaving.