Materiały źródłowe

• #1

  https://www.nhs.uk/conditions/vitamin-b12-or-folate-deficiency-anaemia/

  Vitamin B12 or B9 (commonly called folate) deficiency anaemia occurs when a lack of vitamin B12 or folate causes the body to produce abnormally large red blood cells that cannot function properly. […] There are a number of problems that can lead to a vitamin B12 or folate deficiency. […] Pernicious anaemia where your immune system attacks healthy cells in your stomach, preventing your body absorbing vitamin B12 from the food you eat; this is the most common cause of vitamin B12 deficiency in the UK. […] Both vitamin B12 deficiency and folate deficiency are more common in older people, affecting around 1 in 10 people aged 75 or over and 1 in 20 people aged 65 to 74. […] Although it’s uncommon, vitamin B12 or folate deficiency (with or without anaemia) can lead to complications, particularly if you have been deficient in vitamin B12 or folate for some time.

• #2 Vitamin B12 & folate anaemia | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/nutritional/vitamin-b12-or-folate-deficiency-anaemia/

  Vitamin B12 or B9 (commonly called folate) deficiency anaemia occurs when a lack of vitamin B12 or folate causes the body to produce abnormally large red blood cells that cant function properly. […] Vitamin B12 or folate deficiency anaemia occurs when a lack of either of these vitamins affects the bodys ability to produce fully functioning red blood cells. […] Most people with vitamin B12 or folate deficiency anaemia have underdeveloped red blood cells that are larger than normal. The medical term for this is megaloblastic anaemia. […] Pernicious anaemia causes your immune system to attack the cells in your stomach that produce the intrinsic factor, which means your body is unable to absorb vitamin B12. […] A vitamin B12 or folate deficiency can be the result of a variety of problems, some of which are described below.

• #3 Megaloblastic anaemia: Folic acid and vitamin B12 metabolism | Revista Médica del Hospital General de México

  https://www.elsevier.es/en-revista-revista-medica-del-hospital-general-325-articulo-megaloblastic-anaemia-folic-acid-vitamin-S0185106315000426

  Folic acid and cobalamin are B-group vitamins that play an essential role in many cellular processes. Deficiency in one or both of these vitamins causes megaloblastic anaemia, a disease characterized by the presence of megaloblasts. Megaloblasts occur when inhibition of DNA synthesis causes asynchronous maturation between the nucleus and the cytoplasm. Clinical manifestations are similar to those of other types of anaemia, with the exception of cobalamin deficiency megaloblastic anaemia, which presents distinctive neurological symptoms. An understanding of the metabolism of these vitamins will enable clinicians to make the best use and interpretation of laboratory studies and monitor therapeutic strategies, which consist mainly of administering supplements to restore body reserves. […] […] Megaloblastic anaemia is a general term used to describe a group of anaemias caused by impaired DNA synthesis. It is characterized by abnormal findings in peripheral blood smear (macroovalocytes) and bone marrow samples (megaloblastic hyperplasia). Megaloblasts, the hallmark of these anaemias, are caused by asynchronous maturation between the nucleus and the cytoplasm due to DNA synthesis impairment. […]

• #4 Vitamin B12 Deficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441923/

  Vitamin B12 deficiency can lead to hematologic and neurological symptoms. […] Vitamin B12 deficiency has 4 primary etiologies: […] Autoimmune: Pernicious anemia is an autoimmune condition in which antibodies to intrinsic factors are produced. Anti-intrinsic factor antibodies bind to and inhibit the effects of intrinsic factors, resulting in an inability of B12 to be absorbed by the terminal ileum. […] Vitamin B12 is a cofactor for the enzyme methionine synthase, which is used in the conversion of homocysteine to methionine. As a byproduct of this reaction, methyltetrahydrofuran (methyl-THF) is converted to THF, which is converted to intermediates used in the synthesis of pyrimidine bases of deoxyribonucleic acid (DNA). In B12 deficiency, homocysteine cannot be converted to methionine, and thus, methyl-THF cannot be converted to THF. As a result, homocysteine levels accumulate, and pyrimidine bases cannot be formed, slowing down DNA synthesis and can cause megaloblastic anemia.

• #5 Megaloblastic anaemia: Folic acid and vitamin B12 metabolism | Revista Médica del Hospital General de México

  https://www.elsevier.es/en-revista-revista-medica-del-hospital-general-325-articulo-megaloblastic-anaemia-folic-acid-vitamin-S0185106315000426

  The pathophysiology of this group of anaemias has its origins in ineffective erythropoiesis secondary to intramedullary apoptosis of hematopoietic precursor cells. This, in turn, is caused by DNA synthesis abnormalities. […] […] Remember, both folate and cobalamin deficiency ultimately lead to thymidylate deficiency. DNA contains 2 purine bases (adenine and guanine) and 2 pyrimidine bases (thymine and cytosine). When there is insufficient thymidylate or thymine at the position in the DNA strand where these nitrogenous bases should occur, they are replaced by uracil. This happens primarily when uracil is incorporated at 2 similar positions in opposite strands. When uracil is incorporated into what should be a purely DNA structure, the repair enzymes detect the error and try to correct it, albeit unsuccessfully. As a result, first 1, then both DNA strands are destroyed, with the resulting p53-mediated cellular apoptosis. […]

• #5 Vitamin B12 Deficiency: Recognition and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/0915/p384.html

  Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. […] Vitamin B12 (cobalamin) is crucial for neurologic function, red blood cell production, and DNA synthesis, and is a cofactor for three major reactions: the conversion of methylmalonic acid to succinyl coenzyme A; the conversion of homocysteine to methionine; and the conversion of 5-methyltetrahydrofolate to tetrahydrofolate. […] Pernicious anemia refers to one of the hematologic manifestations of chronic auto-immune gastritis, in which the immune system targets the parietal cells of the stomach or intrinsic factor itself, leading to decreased absorption of vitamin B12. […] Patients diagnosed with vitamin B12 deficiency whose history and physical examination do not suggest an obvious dietary or malabsorptive etiology should be tested for pernicious anemia with anti-intrinsic factor antibodies (positive predictive value = 95%), particularly if other autoimmune disorders are present. […] If vitamin B12 deficiency coexists with folate deficiency, vitamin B12 should be replaced first to prevent subacute combined degeneration of the spinal cord.

• #6 Vitamin B12 Deficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441923/

  Vitamin B12 is also used as a cofactor for the enzyme methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA. In patients with B12 deficiency, methylmalonic acid (MMA) levels will accumulate, as it cannot be converted to succinyl-CoA. A hypothesis states that elevated levels of MMA, along with elevated levels of homocysteine, contribute to myelin damage, accounting for the neurologic deficits, such as neuropathy and ataxia, seen in these patients. […] The impaired DNA synthesis causes problems for other rapidly proliferating cell lines, such as polymorphonuclear leukocytes (PMNs). Thus, B12 deficiency characteristically results in the formation of hypersegmented neutrophils.

• #7 Pernicious anemia – Wikipedia

  https://en.wikipedia.org/wiki/Pernicious_anemia

  The body needs enough intrinsic factor to absorb and reabsorb vitamin B12 from the bile, the lack of which reduces the time needed to develop a deficiency. […] B12 is required by enzymes for two reactions: the conversion of methylmalonyl-CoA to succinyl-CoA, and the conversion of homocysteine to methionine. […] During B12 deficiency, this reaction cannot proceed, which leads to the accumulation of levomefolic acid. […] This accumulation depletes the other types of folate required for purine and thymidylate synthesis, which are required for the synthesis of DNA. […] Inhibition of DNA replication in maturing red blood cells results in the formation of large, fragile megaloblastic erythrocytes. […] The neurological aspects of the disease are thought to arise from the accumulation of methylmalonyl-CoA due to the requirement of B12 as a cofactor to the enzyme methylmalonyl-CoA mutase.

• #8 Megaloblastic Anemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/204066-overview

  Megaloblasts are large nucleated red blood cells. Vitamin B12 deficiency (eg, pernicious anemia), folic acid deficiency, and certain medications are the most common causes of megaloblastic anemia, a macrocytic anemia. […] The common feature in megaloblastosis is a defect in DNA synthesis in rapidly dividing cells. To a lesser extent, RNA and protein synthesis are impaired. Unbalanced cell growth and impaired cell division occur since nuclear maturation is arrested. More mature RBC precursors are destroyed in the bone marrow prior to entering the blood stream (intramedullary hemolysis). […] The most common causes of megaloblastosis are vitamin B12 and folate deficiencies, medications, and direct interference of DNA synthesis by HIV infections and myelodysplastic disorders. […] Diminished activity of methionine synthase or decreased tetrahydrofolate can cause defective DNA maturation and megaloblastic changes.

• #9 Severe megaloblastic anemia: Vitamin deficiency and other causes | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/87/3/153

  The laboratory and clinical findings were consistent with vitamin B12 deficiency, and the presence of anti-intrinsic factor antibody confirmed the diagnosis of pernicious anemia. […] Vitamin B12 deficiency causes hematologic and neuropsychiatric manifestations that may occur together or independently. […] Megaloblastic anemia due to folate deficiency and other causes shares the same hematologic manifestations as vitamin B12 deficiency but lacks the neurologic features. […] The most common hematologic manifestation is megaloblastic anemia, which includes macrocytic erythrocytes in the peripheral blood and megaloblastic precursor cells in the bone marrow that exhibit nuclear-to-cytoplasmic dyssynchrony. […] Ineffective erythropoiesis leads to intramedullary hemolysis, classically with high lactate dehydrogenase and undetectable haptoglobin, but without schistocytes in the peripheral blood.

• #10 Megaloblastic Anemia: Folate Deficiency & Vitamin B12 Deficiency – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/megaloblastic-anemia-folate-deficiency-vitamin-b12-deficiency

  Megaloblastic anemia is primarily caused by a deficiency in folate or vitamin B12, which results in DNA/RNA asynchrony. DNA maturation and cell division become delayed, while RNA translation and protein production continue. This causes the cell division in the red blood cells to be impaired due to poor DNA maturation while the cytoplasm continues to grow, resulting in an increase in the mean cell volume (MCV) and the production of megaloblasts – large nucleated red blood cells. Furthermore, the abnormal red blood cells undergo apoptosis or are phagocytosed by macrophages, leading to fewer red blood cells in circulation. This also explains the low reticulocyte count noticed in patients with this condition. […] Vitamin B12 (cobalamin) is a coenzyme that aids in methyltransferase reactions, including the conversion of homocysteine to methionine. A deficiency in vitamin B12 can cause megaloblastic anemia because insufficient amounts impair red blood cell division and maturation. Causes of vitamin B12 deficiency include following a strict vegan diet, chronic alcohol consumption, conditions that lead to achlorhydria or lack of gastric acid, decreased production of intrinsic factor, pernicious anemia, and conditions affecting the ileum such as Crohn’s disease or parasitic infection by Diphyllobothrium latum. Pancreatic insufficiency can also lead to vitamin B12 deficiency.

• #11 Severe megaloblastic anemia: Vitamin deficiency and other causes | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/87/3/153

  Symptoms secondary to anemia include fatigue, shortness of breath, and poor exercise tolerance. […] Megaloblastic changes are best appreciated with bone marrow aspirate smears using Wright-Giemsa stain. The typical findings in the erythroid lineage include increased overall size and nuclear-cytoplasmic dyssynchrony. […] In severe vitamin deficiency, dysplastic features can be observed, most often involving the erythroid lineage in the form of nuclear irregularities, eg, binucleation, multinucleation, nuclear fragmentation, and nuclear budding, which resemble features seen in myelodysplastic syndrome. […] After establishing the diagnosis, treatment should be initiated promptly. Treatment is specific to the underlying condition and usually involves supplementing the deficient vitamin.

• #12 Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164559

  Megaloblastic anemia (MBA), also known as macrocytic anemia, is characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail to enter blood circulation due to their larger size. Lack of vitamin-B12 (VB12) and / or folate (Vitamin-B9, VB9) with elevated homocysteine is the key factor responsible for megaloblastic anemia. […] Mechanistically, the MBA caused by Folate or Vitamin-B12 deficiency is due to the inhibition of DNA synthesis and induction of apoptosis in pre-erythroblasts, which hinders the transformation of these cells in to reticulocytes thereby ultimately leading to pancytopenia. Elevated apoptosis in pre-erythroblasts is primarily caused by the inability of these cells to repair the DNA damage as well as improper replication.

• #13 Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164559

  One key apoptosis inducer is p53. It is well-established that in addition to the induction of apoptosis in abnormal cells, p53 has a role in the terminal differentiation of normoblasts and maintain the integrity of genetic material by protecting the DNA from various damages as well as from mis-incorporation of nucleotides. […] Therefore, to address whether low VB12 and VB9, confirmed by elevated homocysteine content, correlates with the expression of p53 in megaloblastic anemia, we have measured the levels of vitamin-B9, B12 and homocysteine in the serum of non-MBA control subjects and MBA patients, and quantified the p53 expression using immunohistochemistry of bone marrow biopsies embedded in paraffin blocks. The data showed elevated expression of p53 in all the MBA samples indicating that p53 is the primary cause for the induction of apoptosis in megaloblast cells isolated from pernicious anemia patients.

• #14 Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164559

  In conclusion the results from our study demonstrate that p53 is heavily expressed in the megaloblastic cells of patients suffering from megaloblastic anemia. Elevated p53 expression in MBA is predicted to be due to very low levels of vitamin-B12 and vitamin-B9 in megaloblastic anemia cases compared to controls that are suffering from anemia other than MBA.

• #15 Vitamin B12 Deficiency – Nutritional Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/nutritional-disorders/vitamin-deficiency-dependency-and-toxicity/vitamin-b12-deficiency

  Vitamin B12 deficiency can result from inadequate intake, inadequate absorption, decreased utilization, and use of certain medications. […] Pernicious anemia is often used synonymously with vitamin B12 deficiency. However, pernicious anemia specifically refers to anemia resulting from vitamin B12 deficiency caused by an autoimmune metaplastic atrophic gastritis with loss of intrinsic factor. […] The deficiency commonly causes megaloblastic anemia, loss of position and vibration sensation (which occurs early and progresses), and, when advanced, paranoia, delirium, and confusion. […] Treat with supplemental vitamin B12.

• #16 Pernicious anemia – Wikipedia

  https://en.wikipedia.org/wiki/Pernicious_anemia

  Pernicious anemia refers to a type of vitamin B12 deficiency anemia that results from lack of intrinsic factor. […] Lack of intrinsic factor is most commonly due to an autoimmune attack on the cells that create it in the stomach. […] Because pernicious anemia is due to a lack of intrinsic factor, it is not preventable. […] Pernicious anemia is the most common cause of clinically evident vitamin B12 deficiency worldwide. […] Although the healthy body stores three to five years’ worth of B12 in the liver, the usually undetected autoimmune activity in one’s gut over a prolonged period of time leads to B12 depletion and the resulting anemia; pernicious anemia refers to one of the hematologic manifestations of chronic auto-immune gastritis, in which the immune system targets the parietal cells of the stomach or intrinsic factor itself, leading to decreased absorption of vitamin B12.

• #17 Pernicious Anaemia: Mechanisms, Diagnosis, and Management | EMJ

  https://www.emjreviews.com/hematology/article/pernicious-anaemia-mechanisms-diagnosis-and-management/

  H. pylori are ubiquitous organisms invading the gastric mucosa and are a global burden. They cause superficial gastritis, destruction of gastric parietal cells, and atrophic gastritis, resulting in reduced availability of IF for vitamin B12 transport. This causes an interference with vitamin B12 absorption, thus leading to vitamin B12 deficiency and its clinical manifestations. […] Patients with PA have been shown to have two types of antibodies: one to parietal cells and the other to IF (IFA) or its binding site in the small bowel. […] The immune response is directed against the gastric H+/K+-ATPase, which accounts for the associated achlorhydria. […] The atrophic gastritis is caused by the action of autoreactive CD4+ T cells that recognise H+/K+-ATP ase, which leads to their immune destruction.

• #18 Pernicious Anemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/204930-overview

  Intrinsic factor is a gastric protein secreted by parietal cells that is necessary for vitamin B12 absorption. Pernicious anemia is an autoimmune disorder that leads to insufficient intrinsic factor levels either as a result of auto-antibody mediated destruction of parietal cells and/or the intrinsic factor protein itself. […] Other disorders that interfere with the absorption and metabolism of vitamin B12 can also result in cobalamin deficiency, with the development of a macrocytic anemia and neurologic complications. […] Cobalamin deficiency may result from dietary insufficiency of vitamin B12; disorders of the stomach, small bowel, and pancreas; certain infections; and abnormalities of transport, metabolism, and utilization. […] Classic pernicious anemia produces cobalamin deficiency due to failure of the stomach to secrete IF.

• #19 Vitamin B12 deficiency – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/vitamin-b12-deficiency/

  Anti-intrinsic factor antibodies bind intrinsic factor, blocking the vitamin B12 binding site and most vitamin B12 absorption; a small amount of passive diffusion occurs throughout the intestinal tract. […] In combined vitamin B12 and folate deficiency, folate supplementation without vitamin B12 replacement may exacerbate neurological symptoms, likely due to ongoing damage from untreated vitamin B12 deficiency.

• #20 Vitamin B12 deficiency – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/vitamin-b12-deficiency/

  Methionine synthase demethylates 5-methyltetrahydrofolate, producing tetrahydrofolic acid, a cofactor in purine synthesis, and also converts homocysteine to methionine. […] Tetrahydrofolic acid DNA synthesis impaired hematopoiesis. […] Large, nucleated hematopoietic cells, including megaloblasts, are produced, which undergo apoptosis or are phagocytosed by macrophages. […] AIG causes chronic destruction of gastric parietal cells, leading to mucosal atrophy, achlorhydria, and loss of intrinsic factor. Vitamin B12 deficiency is a late manifestation of AIG, termed pernicious anemia. […] The pathophysiology of AIG has not been clearly defined but is associated with: […] Autoreactive T cells target gastric proton pump (H+/K+ ATPase) and are likely the main mediators of inflammation in AIG.

• #21 Severe megaloblastic anemia: Vitamin deficiency and other causes | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/87/3/153

  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 is most commonly caused by folate deficiency from dietary deficiency, alcoholism, or malabsorption syndromes or by vitamin B12 deficiency, usually due to pernicious anemia. […] Both vitamin deficiencies cause hematologic signs and symptoms of anemia; vitamin B12 deficiency also causes neurologic symptoms. […] Nearly every step of this pathway can be disrupted in various pathologic states, but lack of intrinsic factor secondary to pernicious anemia is the cause of vitamin B12 deficiency in most cases. […] Chronic atrophic autoimmune gastritis affects the body and fundus of the stomach, replacing normal oxyntic mucosa with atrophic-appearing mucosa, often with associated intestinal metaplasia.

• #22

  https://www.nhs.uk/conditions/vitamin-b12-or-folate-deficiency-anaemia/causes/

  Vitamin B12 or folate deficiency anaemia occurs when a lack of either of these vitamins affects the body’s ability to produce fully functioning red blood cells. […] Pernicious anaemia causes your immune system to attack the cells in your stomach that produce the intrinsic factor, which means your body is unable to absorb vitamin B12. […] Some conditions that affect your intestines can also stop you absorbing the necessary amount of vitamin B12. […] This results in neurological complications involving the spinal cord. […] Like vitamin B12 deficiency anaemia, folate deficiency anaemia can develop for a number of reasons. […] Sometimes your body may be unable to absorb folate as effectively as it should. […] Your body sometimes requires more folate than normal. This can cause folate deficiency if you cannot meet your body’s demands for the vitamin.

• #23 Vitamin B12 Deficiency | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0301/p979.html

  The classic disorder of malabsorption is pernicious anemia, an autoimmune disease that affects the gastric parietal cells. Destruction of these cells curtails the production of intrinsic factor and subsequently limits vitamin B12 absorption. […] The phenomenon of food-bound malabsorption occurs when vitamin B12 bound to protein in foods cannot be cleaved and released. Any process that interferes with gastric acid production can lead to this impairment. Atrophic gastritis, with resulting hypochlorhydria, is a major cause, especially in the elderly. […] The widespread and prolonged use of histamine H2-receptor blockers and proton pump inhibitors for ulcer disease also may cause impaired breakdown of vitamin B12 from food, causing malabsorption and eventual depletion of B12 stores.

• #24 Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk – GOV.UK

  https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk

  Decreased vitamin B12 levels, or vitamin B12 deficiency, is now considered to be a common side effect in patients on metformin treatment, especially in those receiving a higher dose or longer treatment duration and in those with existing risk factors. […] The mechanism is currently thought to be multifactorial, comprising altered intestinal motility, bacterial overgrowth, and reduced uptake of vitamin B12 within the small intestine (or a combination of these factors). […] Common causes of vitamin B12 deficiency include infections, malabsorption, medical conditions (Crohns disease, pernicious anaemia), gastric resection, and inadequate dietary intake. […] Patients with a vitamin B12 deficiency can be asymptomatic or they can present with symptoms of megaloblastic anaemia or neuropathy or both. Other symptoms of low vitamin B12 levels may include mental disturbance (depression, irritability, cognitive impairment), glossitis (swollen and inflamed tongue), mouth ulcers, and visual and motor disturbances. It is important for patients with anaemia or neuropathy caused by vitamin B12 deficiency to be diagnosed and treated as soon as possible to avoid the development of permanent symptoms.

• #25 Vitamin B12 Deficiency – Nutritional Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/nutritional-disorders/vitamin-deficiency-dependency-and-toxicity/vitamin-b12-deficiency

  Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage to the white matter of the spinal cord and brain, and peripheral neuropathy. Diagnosis is usually made by measuring serum vitamin B12 levels. The Schilling test helps determine etiology. Treatment consists of oral or parenteral vitamin B12. Folate (folic acid) should not be used instead of vitamin B12 because folate may alleviate the anemia but allow neurologic deficits to progress. […] Inadequate absorption may occur in small intestinal bacterial overgrowth (blind loop syndrome) or fish tapeworm infestation; in these cases, bacteria or parasites use ingested vitamin B12 so that less is available for absorption.

• #26 Cobalamin (vitamin B12) and Folate Deficiency – Province of British Columbia

  https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12

  B12 deficiency can cause preventable permanent injury and should be considered with new onset neurological conditions and symptoms suggestive of B12 deficiency (See Low B12 symptoms section below). […] A specific form of malabsorption, pernicious anemia, is caused by autoimmunity to intrinsic factor resulting in failure to absorb dietary B12. Other causes for malabsorption include Crohns disease, celiac disease, and medication interactions (e.g., proton pump inhibitor, metformin). […] Manifestations of vitamin B12 deficiency may be mild, such as fatigue and heart palpitations, but may progress to neurological manifestations, including peripheral neuropathy and dementia-like symptoms. […] In suspected B12 deficiency, supplement both B12 and folate. […] Early treatment of B12 deficiency is particularly important because neurologic symptoms may be irreversible.

• #27 Vitamin B12 or folate deficiency anaemia

  https://www2.hse.ie/conditions/vitamin-b12-or-folate-deficiency-anaemia/

  Vitamin B12 or B9 (folate) deficiency anaemia happens when you have a shortage of either of these vitamins. The body responds by producing abnormally large red blood cells that do not function properly. […] Several other causes can lead to a vitamin B12 or folate deficiency. […] Pernicious anaemia is where your immune system attacks healthy cells in your tummy. This prevents your body from absorbing vitamin B12 from the food you eat. It’s the most common cause of vitamin B12 deficiency. […] Coeliac disease is a condition where your immune system attacks your own tissues when you eat gluten. This can also lead to B12 deficiency anaemia. […] Vitamin B12 or folate deficiency can lead to complications. But this is not common. […] Complications are more likely if you have a deficiency in the vitamin for some time. Some will improve with the right treatment. Others can be permanent, such as problems with the nervous system.

• #28 Vitamin B12 deficiency – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/vitamin-b12-deficiency/

  Vitamin B12 deficiency is caused by insufficient dietary intake, malabsorption, or increased demand and can result in megaloblastic anemia and various neurological disturbances. […] Pernicious anemia is the most common type of vitamin B12 deficiency and is caused by autoimmune gastritis (AIG). Vitamin B12 deficiency in AIG is due to mucosal atrophy, achlorhydria, and loss of intrinsic factor, which is crucial for vitamin B12 absorption. […] Malabsorption, autoimmune gastritis (pernicious anemia), gastrectomy, gastric bypass, nitric oxide misuse, and inherited disorders can cause severe vitamin B12 deficiency. […] Vitamin B12 is a water-soluble cofactor for enzymes involved in DNA synthesis (i.e., methionine synthase) and odd-chain fatty acid metabolism (i.e., methylmalonyl-CoA mutase), and deficiency leads to enzymatic dysfunction. Enzymatic dysfunction has the following consequences:

• #29 Anaemia, vitamin B12 and folate deficiency | Nursing Times

  https://www.nursingtimes.net/archive/anaemia-vitamin-b12-and-folate-deficiency-06-02-2009/

  Anaemia is a condition that occurs when there is a reduced number of red blood cells or concentration of haemoglobin. […] Other forms of anaemia can be caused by a lack of vitamin B12 or folate in your body. […] This article concentrates on vitamin-B12-and-folate-deficiency anaemia. […] Vitamin B12 not only helps your body to produce red blood cells, it also helps keep your nervous system healthy. Folate works with vitamin B12 to produce red blood cells, and it is also important for pregnant women, as it helps the baby to grow and develop. […] A vitamin B12 deficiency is rare in younger people, and is most common in people who are over 75 years of age. Folate deficiency is also most common in people over 75 years of age. People following a strict vegan diet tend to be more at risk of developing a vitamin B12 deficiency.

• #30 Folate and vitamin B12: friendly or enemy nutrients for the elderly* | Proceedings of the Nutrition Society | Cambridge Core

  https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/folate-and-vitamin-b12-friendly-or-enemy-nutrients-for-the-elderly/D8C38CD6D49977957C5B098623459519

  In the UK vitamin B12 deficiency occurs in approximately 20% of adults aged 65 years. This incidence is significantly higher than that among the general population. […] The reported incidence invariably depends on the criteria of deficiency used, and in fact estimates rise to 24% and 46% among free-living and institutionalised elderly respectively when methylmalonic acid is used as a marker of vitamin B12 status. […] It is argued that consuming additional folic acid (as synthetic pteroylglutamic acid) from fortified foods increases the risk of masking megaloblastic anaemia caused by vitamin B12 deficiency. […] The relationship between impairment of the methylation cycle and a lack of DNA biosynthesis and anaemia is explained by the methyl trap hypothesis. […] Thus, in PA there will be a neuropathy and/or anaemia.

• #31 Pathology Outlines – Folate deficiency anemia

  https://www.pathologyoutlines.com/topic/hematofolatedefanemia.html

  Folate deficiency is a low level of folic acid (Vitamin B9) in the body […] Characterized by macrocytic anemia […] Also called Vitamin B9 deficiency […] Inadequate ingestion of folate containing foods due to: alcoholism (alcohol dehydrogenase binds folate), psychiatric morbidities, elderly […] Impaired absorption: celiac disease, tropical sprue, achlorhydria, anticonvulsant drugs (Dilantin), zinc deficiency, bacterial overgrowth in blind loops, strictures, jejunal diverticula […] Impaired metabolism, leading to inability to utilize absorbed folate: methotrexate and trimethoprim (folate antagonists) […] Hypothyroidism (decreases hepatic levels of dihydrofolate reductase) […] Congenital deficiency of enzymes of folate metabolism […] Increased requirement: infancy, pregnancy, lactation, malignancy, concurrent infection (immunoproliferative response), chronic hemolytic anemia (increased hematopoiesis)

• #32 Anaemia, vitamin B12 or folate deficiency – Causes of vitamin B12 or folate

  https://www.ibdrelief.com/learn/complications-of-ibd/vitamin-and-mineral-deficiencies-in-ibd/vitamin-b12-and-ibd/anaemia-vitamin-b12-or-folate-deficiency-causes-of-vitamin-b12-or-folate-deficiency-anaemia

  Like vitamin B12 deficiency anaemia, folate deficiency anaemia can develop for a number of reasons. […] Folate deficiency caused by a lack of dietary folate is more common in people who have a generally unbalanced and unhealthy diet, people who regularly misuse alcohol and people following a fad diet that doesn’t involve eating good sources of folate. […] Sometimes your body may be unable to absorb folate as effectively as it should. […] Some types of medicine reduce the amount of folate in your body, or make the folate harder to absorb. […] Your body sometimes requires more folate than normal. […] If you are pregnant or trying to get pregnant, it is recommended that you take a 400 microgram folic acid tablet every day until you are 12 weeks pregnant. […] If you are pregnant and have another condition that may increase your body’s need for folate, such as those mentioned above, your GP will monitor you closely to prevent you from becoming anaemic.

• #33 Folate Deficiency: Recognize Symptoms & Causes | Ada

  https://ada.com/conditions/folate-deficiency/

  Megaloblasts are large, poorly-formed red blood cells that form in cases of anemia caused by, among others, folate or B12 deficiencies. Megaloblastic anemia is a result of folate deficiency as well as one of the most easily-identified symptoms: sometimes, a deficiency is only identified when anemia presents. If it results from folate deficiency, this anemia, is treated by taking oral or intravenous folate supplements. […] […] Folic acid is very important in the correct development of cells and is crucial for the correct development of fetuses. Pregnant women and women planning to become pregnant should increase their folic acid intake to 400 micrograms a day. […] […] Folic acid deficiency in the mother can cause defects in the neural tube, which is the structure that eventually develops into the baby’s spinal cord. Neural tube defects (NTDs) can include spina bifida, caudal regressive (affecting the lowest part of the spine), and cleft palate. […]

• #34 Vitamin B12 & folate anaemia | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/nutritional/vitamin-b12-or-folate-deficiency-anaemia/

  A lack of vitamin B12 (with or without anaemia) can cause neurological problems (issues affecting your nervous system), such as vision problems, memory loss, and pins and needles (paraesthesia). […] A lack of folate (with or without anaemia) can also cause complications, some of which are outlined below.

• #35 Pernicious Anemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK540989/

  Pernicious anemia is a relatively rare autoimmune disorder that causes diminishment in dietary vitamin B12 absorption, resulting in B12 deficiency and subsequent megaloblastic anemia. […] The primary pathophysiological mechanism in pernicious anemia is diminished dietary B12 absorption due to IF deficiency. Vitamin B12 is found in meat, eggs, and dairy products and is essential for erythropoiesis and nerve myelination; therefore, its deficiency can lead to megaloblastic anemia due to disrupted DNA synthesis and demyelinated nerves. […] Vitamin B12 deficiency prevents the proper functioning of these coenzymes, leading to an accumulation of their substrate in plasma. Specifically, adenosylcobalamin deficiency results in an accumulation of methylmalonic acid (MMA), and methylcobalamin deficiency in an accumulation of homocysteine. […] Elevated plasma total homocysteine is associated with white matter damage, neurofibrillary tangles, brain atrophy, cognitive decline, and dementia. […] The effects of accumulated MMA are unclear.

• #36 Megaloblastic anaemia: Folic acid and vitamin B12 metabolism | Revista Médica del Hospital General de México

  https://www.elsevier.es/en-revista-revista-medica-del-hospital-general-325-articulo-megaloblastic-anaemia-folic-acid-vitamin-S0185106315000426

  Folic acid deficiency is usually due to low folate content in the diet, or to an imbalance between folate demand and intake. Cobalamin deficiency is usually caused by poor absorption of this vitamin in the digestive tract. […] […] Cobalamin deficiency causes subacute combined degeneration of the posterior and lateral grey column of the spinal cord due to methionine deficiency. Methionine is needed for the production of myelin. Myelin deficiency causes demyelination and gliosis of the grey column, which is further aggravated by the neurotoxicity of methylmalonic acid. Elevation of tumour necrosis factor alpha and epidermal growth factor also contribute to neurological changes.

• #37 Vitamin deficiency anemia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/vitamin-deficiency-anemia/symptoms-causes/syc-20355025

  A folate deficiency can occur when people don’t eat foods containing folate or their bodies are unable to absorb folate from food. […] Absorption problems may be caused by: […] A lack of folate can cause birth defects during pregnancy. […] Being deficient in vitamin B-12 or folate increases your risk of many health problems, including: […] Untreated, vitamin B-12 deficiency can lead to neurological problems, such as persistent tingling in the hands and feet or problems with balance. It can lead to mental confusion and forgetfulness because vitamin B-12 is necessary for healthy brain function. […] Pernicious anemia increases the risk of stomach or intestinal cancers.

• #38 Megaloblastic Anemia: Folate Deficiency & Vitamin B12 Deficiency – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/megaloblastic-anemia-folate-deficiency-vitamin-b12-deficiency

  Vitamin B12 deficiency can cause neuropsychiatric impairment due to its role in myelin synthesis, which is crucial for the proper functioning of nerve cells. This leads to subacute combined degeneration, characterized by injury to both the dorsal and lateral columns due to demyelination. The motor pathways in the lateral pyramidal tracts and the sensory pathways in the dorsal spinal column also degenerate, causing symptoms such as weakness, paralysis, paresthesias, numbness, and sensory ataxia.

• #39 Vitamin B12 Deficiency | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0301/p979.html

  Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. […] Vitamin B12 deficiency is associated with hematologic, neurologic, and psychiatric manifestations. It is a common cause of macrocytic (megaloblastic) anemia and, in advanced cases, pancytopenia. Neurologic sequelae from vitamin B12 deficiency include paresthesias, peripheral neuropathy, and demyelination of the corticospinal tract and dorsal columns (subacute combined systems disease). Vitamin B12 deficiency also has been linked to psychiatric disorders, including impaired memory, irritability, depression, dementia and, rarely, psychosis. […] In addition to hematologic and neuropsychiatric manifestations, vitamin B12 deficiency may exert indirect cardiovascular effects. Similar to folic acid deficiency, vitamin B12 deficiency produces hyperhomocysteinemia, which is an independent risk factor for atherosclerotic disease.

• #40 Vitamin B12 deficiency anemia: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000574.htm

  Vitamin B12 deficiency anemia is a low red blood cell count due to a lack (deficiency) of vitamin B12. […] Your body needs vitamin B12 to make red blood cells. In order to provide vitamin B12 to your cells: […] Certain health conditions can make it difficult for your body to absorb enough vitamin B12. They include: […] Pernicious anemia, a condition that occurs when your body destroys cells in your stomach that make intrinsic factor, which may lead to vitamin B12 deficiency and anemia. […] Long-term vitamin B12 deficiency can cause nerve damage. This may be permanent if you do not start treatment promptly after your symptoms begin. […] Vitamin B12 deficiency anemia most often responds well to treatment. It will likely get better when the underlying cause of the deficiency is treated.

• #41 Vitamin B12 Deficiency Anaemia – Armando Hasudungandownloadbookprintpencilchevron-leftchevron-righttwitterfacebookhand-o-rightfilterchainlist-ulenvelopelinkedinangle-rightangle-upyoutubexinginstagramlong-arrow-uppaper-planepinterest-pwhatsappcommentingadd

  https://armandoh.org/disease/pernicious-anaemia/?srsltid=AfmBOoqIqEJeIzhqEFheK8rAw35zv6DvJNpU88_V6eOygTYh2ShY5ozv

  Vitamin B12 deficiency is a common cause of megaloblastic anemia, a variety of neuropsychiatric symptoms, and elevated serum homocysteine levels, especially in older persons. […] The recognition and treatment of vitamin B12 deficiency is critical since it is a reversible cause of bone marrow failure and demyelinating nervous system disease. […] Vitamin B12 deficiency results in: Slow DNA synthesis → Delayed nuclear maturation → Megaloblastic erythropoiesis → Megaloblastic red blood cells → Anemia. […] Lack of IF leads to Vitamin B12 malabsorption. […] Immune system attacks Parietal cells, IF or IF receptors resulting in IF deficiency. […] Vitamin B12 (Cobalamin) is an essential vitamin responsible for many physiological processes in our body. Vitamin B12 deficiency causes megaloblastic anemia and may be accompanied by neurological abnormalities. […] Pernicious Anaemia is a condition where there is lack of intrinsic factor, a glycoprotein responsible for the absorption of Vitamin B12.

• #42 Anaemia, vitamin B12 and folate deficiency | Nursing Times

  https://www.nursingtimes.net/archive/anaemia-vitamin-b12-and-folate-deficiency-06-02-2009/

  Nutrients from food, such as iron, and vitamins such as B12 and folate (also known as folic acid), help ensure that your bone marrow remains healthy and is able to produce a constant supply of red blood cells. […] The body usually stores enough vitamin B12 to last for approximately two to four years. However, it is important that you have vitamin B12 in your diet in order to ensure that this store of the vitamin is kept at a healthy level. […] Pernicious anaemia is the most common cause of vitamin B12 deficiency. Pernicious anaemia is an autoimmune disease that affects your stomach. […] Vitamin B12 is absorbed into your body through your stomach. The vitamin combines with a protein substance called intrinsic factor so that it can be absorbed from the food that you eat. If your body does not produce enough intrinsic factor, it will not be able to absorb enough vitamin B12.

• #43 Folate and vitamin B12: friendly or enemy nutrients for the elderly* | Proceedings of the Nutrition Society | Cambridge Core

  https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/folate-and-vitamin-b12-friendly-or-enemy-nutrients-for-the-elderly/D8C38CD6D49977957C5B098623459519

  The most important benefit of folic acid fortification of staple foods (such as flour) is its ability to optimize folic acid intakes without any need for the consumer to change his/her food intake. […] The USA has chosen to use PGA as the form of folic acid to add to flour and cereals, possibly on the grounds of cost, and while early data suggest that NTD incidence has decreased appreciably, a number of arguments against fortification have been proposed based on the metabolism of PGA by human subjects. […] Accepting that vitamin B12 deficiency may only manifest clinically in some patients as neurological damage, it has been suggested that administration of high doses of folic acid might have precipitated neurological degeneration. […] It is not possible to predict the effect on the incidence of irreversible vitamin B12 neuropathy, although arguments can be put forward to suggest it might increase as a result of a delay in the diagnosis, which can depend on detecting anaemia.

• #44 Please note the change to our email address as of July 2022:

  https://www.haiderian.co.uk/info.aspx?p=15

  Folic acid, known as folate in its natural form, is one of the B-group vitamins. […] Folic acid has several important functions. For example, it: […] works together with vitamin B12 to form healthy red blood cells. […] A lack of folic acid could lead to folate deficiency anaemia. […] Taking doses of folic acid higher than 1mg can disguise vitamin B12 deficiency. […] An early symptom of vitamin B12 deficiency is anaemia. However, taking large amounts of folic acid treats the anaemia without treating the B12 deficiency. If a vitamin B12 deficiency is not noticed, it can eventually damage the nervous system. […] A lack of vitamin B12 could lead to vitamin B12 deficiency anaemia.

• #45 Vitamin B12 (Cobalamin) Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/supplement/vitamin-b12-cobalamin

  Vitamin B12 is an especially important vitamin for maintaining healthy nerve cells, and it helps in the production of DNA and RNA, the body’s genetic material. Vitamin B12 works closely with vitamin B9, also called folate or folic acid, to help make red blood cells and to help iron work better in the body. […] Severe deficiency of B12 causes nerve damage. […] Pernicious anemia is a type of anemia that happens when stomach cells are not able to make intrinsic factor. Without intrinsic factor, your body cannot absorb vitamin B12. Symptoms include: […] Vitamin B12 supplements in high doses, either given as injections or orally, are prescribed to treat pernicious anemia. […] Folic acid (vitamin B9), especially when taken in high doses, can mask the symptoms of a vitamin B12 deficiency. The danger is that without symptoms, someone with a vitamin B12 deficiency may not know it, and could run the risk of developing nerve damage.

• #46 Pernicious Anaemia – Zero To Finals

  https://zerotofinals.com/medicine/haematology/perniciousanaemia/

  Vitamin B12 deficiency causes macrocytic anaemia. The key causes of a low B12 are: […] Pernicious anaemia is an autoimmune condition involving antibodies against the parietal cells or intrinsic factor. […] In pernicious anaemia, autoantibodies target either the parietal cells or intrinsic factor, resulting in a lack of intrinsic factor and a lack of absorption of vitamin B12. […] Where there is B12 and folate deficiency together, it is essential to treat the B12 deficiency first before correcting the folate deficiency. Giving patients folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord, with demyelination in the spinal cord and severe neurological problems.

• #47 Folate-deficiency anemia: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000551.htm

  Folate-deficiency anemia is a decrease in red blood cells (anemia) due to a lack of folate. Folate is a type of B vitamin. It is also called folic acid. […] In folate-deficiency anemia, the red blood cells are abnormally large. Such cells are called macrocytes. They are also called megaloblasts, when they are seen in the bone marrow. That is why this anemia is also called a type of megaloblastic anemia. […] Folic acid is needed to help a baby in the womb grow properly. Too little folic acid during pregnancy may lead to birth defects in a baby. […] The goal is to identify and treat the cause of the folate deficiency. […] Folate-deficiency anemia most often responds well to treatment within 3 to 6 months. It will likely get better when the underlying cause of the deficiency is treated. […] In pregnant women, folate deficiency has been associated with neural tube or spinal defects (such as spina bifida) in the infant.

• #48 Pernicious Anemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/204930-overview

  In adults, pernicious anemia is associated with severe gastric atrophy and achlorhydria, which are irreversible. […] The achlorhydria results in a decrease in the release of cobalamin bound to dietary protein. […] Autoimmune phenomena and thyroid disease frequently are observed. Patients with pernicious anemia have a 2- to 3-fold increased incidence of gastric carcinoma.

• #49 Vitamin B12 Deficiency: Signs, Causes and Treatments | Ada

  https://ada.com/conditions/vitamin-b12-deficiency/

  Taking a lot of folic acid can mask the symptoms of a vitamin B12 deficiency, so in cases where folate deficiency is suspected, a doctor will usually test for vitamin B12 deficiency before prescribing medication. […] Sometimes blood tests will show normal serum levels of vitamin B12, but a person may experience symptoms and complications related to a deficiency. This can be known as functional vitamin B12 deficiency. In these cases, there may be an issue with the processing of vitamin B12 in the body. […] Treatment will depend on the reasons for the vitamin B12 deficiency. In most cases, having injections or taking a prescribed oral supplement will be sufficient to treat the condition. […] A vitamin B12 deficiency may cause women to be unable to fall pregnant. However, this is usually reversible with treatment. […] In cases of vitamin B12 deficiency caused by pernicious anemia, the risk of developing stomach cancer may be increased. […] Occasionally, a vitamin B12 deficiency can cause complications. These depend on the severity and duration of the deficiency, but may include neurological problems.

• #50 Vitamin deficiency anemia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/vitamin-deficiency-anemia/symptoms-causes/syc-20355025

  Vitamin deficiency anemia is a lack of healthy red blood cells caused by lower than usual amounts of vitamin B-12 and folate. […] This can happen if you don’t eat enough foods containing vitamin B-12 and folate, or if your body has trouble absorbing or processing these vitamins. […] Without these nutrients, the body produces red blood cells that are too large and don’t work properly. This reduces their ability to carry oxygen. […] Vitamin deficiency anemia can occur if you don’t eat enough foods containing vitamin B-12 and folate, or if your body has trouble absorbing or processing these vitamins. […] Low levels of vitamin B-12 can be caused by: […] Pernicious anemia. This condition occurs when the body’s immune system attacks cells in the stomach that produce a substance called intrinsic factor. Without this substance, B-12 can’t be absorbed in the intestines.

• #51 Vitamin B12 Deficiency: Causes, Symptoms, and Treatment

  https://www.webmd.com/diet/vitamin-b12-deficiency-symptoms-causes

  Vitamin B12 does a lot of important things for your body. It helps create your DNA and red blood cells, for example. Your body also needs B12 for the development of your central nervous system (your brain and spinal cord). It also helps keep your hair, nails, and skin healthy. […] You need B12 to make healthy red blood cells, white blood cells, and platelets. Every day, about 1% of your oldest red blood cells are destroyed and replaced. New red blood cells need vitamin B12 and folate (vitamin B9) to grow and develop. If you’re lacking these vitamins, making DNA is hard, causing the immature red blood cells to die. This leads to anemia. […] Vitamin B12 deficiency is associated with cognitive problems (problems with thinking, judgment, and learning) and memory issues. So, it may play a role in conditions such as Alzheimer’s disease and stroke.

• #52 Vitamin B12 Deficiency: Causes, Symptoms, and Treatment

  https://www.webmd.com/diet/vitamin-b12-deficiency-symptoms-causes

  Several autoimmune diseases can make it harder for your body to absorb B12, including pernicious anemia. It’s when your body can’t make intrinsic factor, the protein needed to absorb B12. Another autoimmune disease, atrophic gastritis, thins the lining of your stomach and prevents your body from making enough hydrochloric acid and intrinsic factor you need to absorb B12. […] If you don’t treat your B12 deficiency, it can lead to more severe neurological problems, including: Problems walking or speaking, Vision loss, Numbness or tingling, Muscle weakness, Difficulty remembering things, Depression or mood swings. […] For most people, treatment resolves the problem. But if you have nerve damage from your lack of B12, it could be permanent.

• #53 Megaloblastic Anaemia Presenting as Pyrexia: An Interesting Case Report | Jain | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/53/44

  Megaloblastic anemia is a rare cause of pyrexia. We report the case of a patient who presented with fever, anemia and thrombocytopenia. […] Vitamin B12 and folic Acid deficiency is a rare but treatable cause of fever of unknown cause that responds well to the treatment. Increased activity within bone marrow and defect in oxygenation to temperature regulatory area are proposed mechanisms. It should be considered in any patient who presents with pyrexia with pancytopenia. […] The exact cause of fever in megaloblastic anemia is still elusive and many hypothesis has been put forward in the past. The fever was previously attributed either to some defect in the temperature control mechanism of brain or to poor oxygenation of the temperature regulatory area secondary to vitamin B12 or folic acid deficiency.

• #54 Megaloblastic Anaemia Presenting as Pyrexia: An Interesting Case Report | Jain | Journal of Hematology

  https://thejh.org/index.php/jh/article/view/53/44

  Megaloblastic bone marrow changes are associated with striking intramedullary hemolysis and possibly ineffective leukopoiesis and thrombopoiesis. Thus increased activity in bone marrow may be related to systemic pyrexia. The mechanism of how fever is induced by the overproduction marrow is not known. […] Measurement of Vit B12 and folate levels should be considered in all patients of pyrexia with features of megaloblastic anemia and/or pancytopenia after ruling out infections, inflammatory and endocrine causes. […] Megaloblastic anemia is rare but a known and treatable cause of fever. After ruling out infections and inflammatory conditions, which are important causes of fever in patients having pancytopenic picture, we should consider this possibility to be the etiological cause of fever.

• #55

  https://111.wales.nhs.uk/encyclopaedia/a/article/anaemia,vitaminb12andfolatedeficiency

  Vitamin B12 or B9 (commonly called folate) deficiency anaemia occurs when a lack of vitamin B12 or folate causes the body to produce abnormally large red blood cells that cannot function properly. […] Vitamin B12 or folate deficiency anaemia occurs when a lack of either of these vitamins affects the body’s ability to produce fully functioning red blood cells. […] Pernicious anaemia causes your immune system to attack the cells in your stomach that produce the intrinsic factor, which means your body is unable to absorb vitamin B12. […] A vitamin B12 or folate deficiency can be the result of a variety of problems. […] A diagnosis of vitamin B12 or folate deficiency anaemia can often be made by a GP based on your symptoms and the results of blood tests. […] If your symptoms and blood test results suggest a vitamin B12 or folate deficiency, your GP may arrange further tests.

• #56 Vitamin B12 | Pathology Tests Explained

  https://pathologytestsexplained.org.au/ptests.php?q=Vitamin+B12

  These are two tests that measure the levels of vitamin B12 and folate in your blood. They are usually ordered if you have had an abnormal result from a Full Blood Count test that shows decreased haemoglobin levels, and/or large red blood cells or abnormal white blood cells and you have symptoms of anaemia or neuropathy nerve damage. The tests can also be used as part of a pregnancy screen as during pregnancy a woman needs more B12 and folate to cater for the growing baby. […] A deficiency in either vitamin B12 or folate can lead to a form of anaemia called macrocytic anaemia. This is when your body produces larger but fewer red blood cells with the result that your blood is unable to carry as much oxygen as it should. […] Another type of macrocytic anaemia called megaloblastic anaemia involves changes in the bone marrow. In this case, your test results will also show lower numbers of white blood cells, red blood cells and platelets.

• #57 Vitamin deficiency anemia – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/vitamin-deficiency-anemia/diagnosis-treatment/drc-20355031

  To help diagnose vitamin deficiency anemias, you might have blood tests that check for: […] The amount of vitamin B-12 and folate in the blood […] Vitamin deficiency anemia is treated with doses of whichever vitamin is lacking. For pernicious anemia, vitamin B-12 is usually delivered via injection and may need to be taken regularly for the rest of your life. […] Medications to boost folate levels usually come as pills to be swallowed, but some versions can be delivered through a narrow, flexible tube into a vein (intravenously). […] Causes and pathophysiology of vitamin B12 and folate deficiency.

• #58 Anaemia, vitamin B12 and folate deficiency | Nursing Times

  https://www.nursingtimes.net/archive/anaemia-vitamin-b12-and-folate-deficiency-06-02-2009/

  Once your GP has determined that you have vitamin B12 or folate deficiency anaemia, they may have to carry out further tests to help establish the underlying cause of your deficiency. […] For example, vitamin B12 deficiency is most commonly caused when the antibodies in your immune system (which usually protect against and fight infection) start to attack cells in your stomach, which help your body to absorb the vitamin. […] A lack of vitamin B12 can affect your nervous system. […] A deficiency in these vitamins can result in complications, particularly if you have been deficient in vitamin B12 or folate for some time.

• #59 Megaloblastic Macrocytic Anemias – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/megaloblastic-macrocytic-anemias

  Megaloblastic anemias result most often from deficiencies of vitamin B12 and folate. […] Macrocytic (ie, MCV 100 fL) anemias due to vitamin B12 deficiency or folate deficiency are megaloblastic. […] The most common causes of megaloblastic, macrocytic anemia are deficiency or defective utilization of vitamin B12 or folate. […] Megaloblastic states result from defective DNA synthesis. […] Dyspoiesis results in intramedullary cell death, making erythropoiesis ineffective. […] Because dyspoiesis affects all cell lines, reticulocytopenia and, during later stages, leukopenia and thrombocytopenia develop. […] Howell-Jolly bodies (residual fragments of the nucleus) are usually present. […] If vitamin B12 deficiency is confirmed, testing for the presence of autoantibodies to intrinsic factor should be done. […] Treat the cause of B12 or folate deficiency.

• #60 Pernicious Anemia Presenting With Pancytopenia and Hemolysis: A Case Report | Gladstone | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/3269/2563

  The most common cause of deficiency is pernicious anemia. Pernicious anemia is caused by autoantibodies targeting intrinsic factor or gastric parietal cells. […] Diagnosing deficiency usually begins with testing of the serum vitamin B12 level. The Schilling test is not routinely used anymore. Confirmation of deficiency should be performed by measuring levels of homocysteine and methylmalonic acid. Both will be elevated in vitamin B12 deficiency, as opposed to folate deficiency where MMA will be normal. […] In this case, the patient presented with many classical features of vitamin B12 deficiency. The best initial clue was his MCV of 119 fL. While vitamin B12 deficiency does not always present with an elevated MCV, an MCV of 120 fL is 99% specific for vitamin B12 deficiency.

• #61 Anaemia, vitamin B12 or folate deficiency – Causes of vitamin B12 or folate

  https://www.ibdrelief.com/learn/complications-of-ibd/vitamin-and-mineral-deficiencies-in-ibd/vitamin-b12-and-ibd/anaemia-vitamin-b12-or-folate-deficiency-causes-of-vitamin-b12-or-folate-deficiency-anaemia

  Some people can develop a vitamin B12 deficiency as a result of not getting enough vitamin B12 from their diet. […] Some stomach conditions or stomach operations can prevent the absorption of enough vitamin B12. […] Some conditions that affect your intestines can also stop you from absorbing the necessary amount of vitamin B12. […] Some types of medicine can lead to a reduction in the amount of vitamin B12 in your body. […] Some people can experience problems related to a vitamin B12 deficiency, despite appearing to have normal levels of vitamin B12 in their blood. […] This can occur due to a problem known as functional vitamin B12 deficiency – where there is a problem with the proteins that help transport vitamin B12 between cells. This results in neurological complications involving the spinal cord.

• #62 Pathology Outlines – Folate deficiency anemia

  https://www.pathologyoutlines.com/topic/hematofolatedefanemia.html

  Increased excretion/loss: vitamin B12 deficiency (causes „folate trap”), chronic alcoholism (increased excretion of folate into bile), hemodialysis (may have excess folate loss) […] Increased destruction: superoxide can inactivate folate […] Important to rule out cobalamin (Vitamin B12) deficiency because folate treatment will not improve neurologic abnormalities due to cobalamin deficiency […] Bone marrow biopsy and aspirate may show a hypercellular bone marrow with a megaloblastic maturation of cells, which morphologically resembles changes of vitamin B12 deficiency.

• #63 Vitamin B12 | Pathology Tests Explained

  https://pathologytestsexplained.org.au/ptests.php?q=Vitamin+B12

  Testing for vitamin B12 and folate may be used to help assess your nutritional status if you have signs of malnutrition or malabsorption. This can be associated with alcoholism and the various conditions that cause malabsorption in the intestine, including: […] With pernicious anaemia, the body’s immune system destroys the intrinsic factor significantly reducing the amount of vitamin B12 that can be absorbed. […] When someone, especially an elderly person, exhibits mental or behavioural changes such as irritability, confusion, depression and/or paranoia, vitamin B12 and folate may be measured to help diagnose the underlying cause. […] If you have symptoms suggesting nerve damage or impairment, such as tingling, burning, or numbness in your hands or feet, a vitamin B12 test may be requested to look for vitamin B12 deficiency. […] During pregnancy there is a need for more B12 and folate to cater for the rapidly growing baby. If a woman has low folate at the start of pregnancy, it will become even more depleted as time goes on and may lead to premature birth or neural tube birth defects such as spina bifida.

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