Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review

Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.

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Iron deficiency anemia and megaloblastic anemia in obese patients

Romanian Journal of Internal Medicine ◽

10.1515/rjim-2016-0046 ◽

2017 ◽

Vol 55 (1) ◽

pp. 3-7 ◽

Cited By ~ 2

Author(s):

Mahmoud Arshad ◽

Sara Jaberian ◽

Abdolreza Pazouki ◽

Sajedeh Riazi ◽

Maryam Aghababa Rangraz ◽

...

Keyword(s):

Body Mass Index ◽

Morbid Obesity ◽

Iron Deficiency ◽

Vitamin B12 ◽

Iron Deficiency Anemia ◽

Megaloblastic Anemia ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Obese Patients ◽

B12 Deficiency

Abstract Background. The association between obesity and different types of anemia remained uncertain. The present study aimed to assess the relation between obesity parameters and the occurrence of iron deficiency anemia and also megaloblastic anemia among Iranian population. Methods and Materials. This cross-sectional study was performed on 1252 patients with morbid obesity that randomly selected from all patients referred to Clinic of obesity at Rasoul-e-Akram Hospital in 2014. The morbid obesity was defined according to the guideline as body mass index (BMI) equal to or higher than 40 kg/m2. Various laboratory parameters including serum levels of hemoglobin, iron, ferritin, folic acid, and vitamin B12 were assessed using the standard laboratory techniques. Results. BMI was adversely associated with serum vitamin B12, but not associated with other hematologic parameters. The overall prevalence of iron deficiency anemia was 9.8%. The prevalence of iron deficiency anemia was independent to patients’ age and also to body mass index. The prevalence of vitamin B12 deficiency was totally 20.9%. According to the multivariable logistic regression model, no association was revealed between BMI and the occurrence of iron deficiency anemia adjusting gender and age. A similar regression model showed that higher BMI could predict occurrence of vitamin B12 deficiency in morbid obese patients. Conclusion. Although iron deficiency is a common finding among obese patients, vitamin B12 deficiency is more frequent so about one-fifth of these patients suffer vitamin B12 deficiency. In fact, the exacerbation of obesity can result in exacerbation of vitamin B12 deficiency.

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Reticulocyte size in nutritional anemias

Blood ◽

10.1182/blood.v48.5.669.669 ◽

1976 ◽

Vol 48 (5) ◽

pp. 669-677 ◽

Cited By ~ 15

Author(s):

DR Clarkson ◽

EM Moore

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Mean Corpuscular Volume ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Initial Development ◽

Abrupt Decrease ◽

Iron Saturation ◽

Iron Deficient ◽

B12 Deficiency

Abstract Alterations in reticulocyte size occur 2–3 days after the onset of iron deficient or megaloblastic erythropoiesis and precede, by several weeks, changes in mean corpuscular volume (MCV). Iron-deficiency anemia induced in a normal subject by repeated phlebotomies was characterized by the initial development of larger than normal reticulocytes followed by an abrupt decrease in reticulocyte size. Microreticulocytes appeared 3 days after the fall in per cent iron saturation and antedated the decrease in MCV to below normal by 6 wk. Mean reticulocyte size was disproportionately smaller than normal in patients presenting with iron deficiency. In contrast, reticulocyte size increased abruptly in a patient (and rats) 2–3 days after administration of methotrexate. Mean reticulocyte size was disproportionately larger than normal in patients presenting with folate or vitamin B12 deficiency. Specific replacement therapy with iron, folate, or vitamin B12 was quickly followed by normalization of reticulocyte size.

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Two Cases of Vitamin B12 Deficiency Anemia Combined with Iron Deficiency Anemia

Yeungnam University Journal of Medicine ◽

10.12701/yujm.2003.20.2.206 ◽

2003 ◽

Vol 20 (2) ◽

pp. 206

Author(s):

Eun Hae Kim ◽

Hee Soon Cho ◽

Chae Hoon Lee ◽

Kyung Dong Kim ◽

Myung Soo Hyun

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Iron Deficiency Anemia ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

B12 Deficiency

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Evaluation of Parameters of Folic Acid and Vitamin B12 Deficiency in Patients with Iron Deficiency Anemia

Pediatric Research ◽

10.1203/00006450-196805000-00004 ◽

1968 ◽

Vol 2 (3) ◽

pp. 179-186 ◽

Cited By ~ 6

Author(s):

P Vossough ◽

S Leikin ◽

G Purugganan ◽

G Gautier

Keyword(s):

Folic Acid ◽

Iron Deficiency ◽

Vitamin B12 ◽

Iron Deficiency Anemia ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

B12 Deficiency ◽

Evaluation Of Parameters

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Does Cell Size Matter?: Utilizing Mean Cell Volume in Hospitalized Patients As a Screen to Determine Common Causes of Anemia Including Iron Deficiency Anemia, Vitamin B12 and Folate Deficiency

Blood ◽

10.1182/blood.v128.22.2338.2338 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2338-2338 ◽

Cited By ~ 1

Author(s):

Manika Gupta ◽

Kathleen Copley ◽

Michael Keeney ◽

Ian Chin-Yee

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Cell Volume ◽

Iron Deficiency Anemia ◽

Vitamin B12 Deficiency ◽

Folate Deficiency ◽

Deficiency Anemia ◽

Mean Cell Volume ◽

Common Causes ◽

B12 Deficiency

Abstract Background: The approach to anemia is traditionally based on the Mean Cell Volume. Based on this approach anemia is subdivided into microcytic, normocytic and macrocytic causes. This approach may not accurately discern common causes of anemia in hospitalized patients. Previous studies suggest the MCV may not be a sensitive measurement to differentiate iron deficiency anemia (IDA) and megaloblastic anemia due to vitamin B12 or folate deficiency. Methods: In a retrospective, single-centre study at London Health Sciences Center, all adult patients (age 18 years or older) with confirmed IDA, vitamin B12 and folate deficiency and their associated MCV and RDW values at LHSC over a one year period were reviewed. IDA was defined as hemoglobin less than 115 g/l and ferritin less than 30 (M) and 10 (F). Vitamin B12 deficiency was defined as a value of less than 145. Results: 1119 patients were identified with confirmed IDA, B12 or Folate deficiency. 894 patients had IDA of which 564 patients had low MCV (sensitivity 63.1%) and 797 patients had low MCV or high RDW (sensitivity 89.1%). Of the 96 patients with vitamin B12 deficiency anemia, 12 patients had high MCV (sensitivity 12.5%) and 70 patients had high MCV or high RDW (72.9%). Only one of 2244 patients who had RBC folate measured had an actual folate deficiency. Conclusion: Our results confirm that a normal MCV does not exclude IDA or vitamin B12 deficiency. Clinicians need to be aware of the low sensitivity of the MCV as a screen. The sensitivity of MCV for IDA or vitamin B12 deficiency is improved with indices such as RDW. Folate deficiency is rare in North America and should not be routinely ordered for assessment of nutritional anemia. Disclosures No relevant conflicts of interest to declare.

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Clinical manifestations of vitamin B12 deficiency anemia in children from different age groups

Voprosy praktičeskoj pediatrii ◽

10.20953/1817-7646-2020-6-18-26 ◽

2020 ◽

Vol 15 (6) ◽

pp. 18-26

Author(s):

S.O. Falaleeva ◽

◽

A.V. Morgun ◽

M.V. Borisova ◽

E.V. Borisova ◽

...

Keyword(s):

Nervous System ◽

Vitamin B12 ◽

Clinical Manifestations ◽

Vitamin B12 Deficiency ◽

Psychomotor Development ◽

Deficiency Anemia ◽

Muscular Hypotonia ◽

Involuntary Movements ◽

B12 Deficiency ◽

Group 1

Vitamin B12 deficiency affects not only the bone marrow, but also the nervous system. Usually, B12 hypovitaminosis develops slowly during several years, although infants may also have this disorder. Patients and methods. We performed a retrospective analysis of clinical symptoms and results of routine laboratory testing in patients with vitamin B12 deficiency anemia. Our sample included 19 children of 3–24 month age (Group 1) and 9 adolescents (Group 2). All patients were treated in Krasnoyarsk Regional Clinical Center for Maternal and Child Health in 2012–2019. All participants had serum levels of vitamin B12 below 83 pg/mL. Results. All patients from Group 1 were found to have nervous system disorders, including muscular hypotonia (100%), hypo- or adynamia and retardation of motor skills (63%), and hyporeflexia (42%). More than two-thirds of adolescents (67%) had pancytopenia. One-third of children of 3–24 month age (32%) developed involuntary movements during treatment with cyanocobalamin. Conclusion. Vitamin B12 deficiency in infants may manifest itself with neurological disorders that do not correlate with the severity of anemia. Children with muscular hypotonia and delayed psychomotor development should be tested for their serum level of vitamin B12 if all other potential causes of these disorders have been excluded. It is also important to perform differential diagnosis with paroxysmal conditions, including those induced by cobalamin therapy. Key words: anemia, vitamin B12, involuntary movements, hypodynamia, hyporeflexia, hypotonia, pancytopenia, cyanocobalamin

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Reticulocyte size in nutritional anemias

Blood ◽

10.1182/blood.v48.5.669.bloodjournal485669 ◽

1976 ◽

Vol 48 (5) ◽

pp. 669-677

Author(s):

DR Clarkson ◽

EM Moore

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Mean Corpuscular Volume ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Initial Development ◽

Abrupt Decrease ◽

Iron Saturation ◽

Iron Deficient ◽

B12 Deficiency

Alterations in reticulocyte size occur 2–3 days after the onset of iron deficient or megaloblastic erythropoiesis and precede, by several weeks, changes in mean corpuscular volume (MCV). Iron-deficiency anemia induced in a normal subject by repeated phlebotomies was characterized by the initial development of larger than normal reticulocytes followed by an abrupt decrease in reticulocyte size. Microreticulocytes appeared 3 days after the fall in per cent iron saturation and antedated the decrease in MCV to below normal by 6 wk. Mean reticulocyte size was disproportionately smaller than normal in patients presenting with iron deficiency. In contrast, reticulocyte size increased abruptly in a patient (and rats) 2–3 days after administration of methotrexate. Mean reticulocyte size was disproportionately larger than normal in patients presenting with folate or vitamin B12 deficiency. Specific replacement therapy with iron, folate, or vitamin B12 was quickly followed by normalization of reticulocyte size.

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A Study of Erythropoiesis by Combined Morphologic, Quantitative Cytochemical and Autoradiographic Methods

Blood ◽

10.1182/blood.v31.3.304.304 ◽

1968 ◽

Vol 31 (3) ◽

pp. 304-313 ◽

Cited By ~ 51

Author(s):

S. N. WICKRAMASINGHE ◽

E. H. COOPER ◽

D. G. CHALMERS

Keyword(s):

Cell Cycle ◽

Bone Marrow ◽

Iron Deficiency ◽

Vitamin B12 ◽

Iron Deficiency Anemia ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Normal Bone Marrow ◽

Normal Bone ◽

B12 Deficiency

Abstract The relationship between the morphology of human erythropoietic cells and their position in interphase has been studied. In normal bone marrow, pro-normoblasts, basophilic normoblasts and early polychromatic normoblasts were present in all stages of interphase. It has been shown that a significant increase in nuclear size occurs as a cell moves through its cell cycle, in both normal and megaloblastic erythropoiesis. The relative distribution of the basophilic erythropoietic cells and the dividing polychromatic cells, in the various stages of interphase, has been determined in normal bone marrow, vitamin B12 deficiency and iron deficiency anemia. In vitamin B12 deficiency, associated with moderate or severe anemia, there was an increased proportion of cells in G2, and there were several cells with DNA contents that were between the 2c and 4c values, which were not in DNA synthesis as judged by 3H-TdR labeling. These abnormalities were most pronounced in the dividing polychromatic cell group. Similar abnormalities were not present in iron deficiency anemia, indicating that these disturbances were not produced by the presence of anemia per se. The possible relationship between these changes in the cell cycle and the ineffective erythropoiesis seen in anemia due to vitamin B12 deficiency has been discussed.

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Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders

Journal of Clinical Medicine ◽

10.3390/jcm7100304 ◽

2018 ◽

Vol 7 (10) ◽

pp. 304 ◽

Cited By ~ 2

Author(s):

Emmanuel Andrès ◽

Abrar-Ahmad Zulfiqar ◽

Khalid Serraj ◽

Thomas Vogel ◽

Georges Kaltenbach

Keyword(s):

Vitamin B12 ◽

Prospective Studies ◽

Clinical Manifestations ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Cochrane Library ◽

Clinical Approach ◽

Oral Vitamin ◽

Hand Search ◽

B12 Deficiency

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer’s disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn’s disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.

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