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Cleveland Clinic Journal of Medicine Mar 2020Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B)... (Review)
Review
Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B) deficiency and cobalamin (vitamin B) 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.
Topics: Adolescent; Aged; Anemia, Megaloblastic; Avitaminosis; Diagnosis, Differential; Dietary Supplements; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 32127439
DOI: 10.3949/ccjm.87a.19072 -
American Family Physician Sep 2017Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. Screening average-risk adults for...
Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. Screening average-risk adults for vitamin B12 deficiency is not recommended. Screening may be warranted in patients with one or more risk factors, such as gastric or small intestine resections, inflammatory bowel disease, use of metformin for more than four months, use of proton pump inhibitors or histamine H2 blockers for more than 12 months, vegans or strict vegetarians, and adults older than 75 years. Initial laboratory assessment should include a complete blood count and serum vitamin B12 level. Measurement of serum methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. Oral administration of high-dose vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration for correcting anemia and neurologic symptoms. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms. Absorption rates improve with supplementation; therefore, patients older than 50 years and vegans or strict vegetarians should consume foods fortified with vitamin B12 or take vitamin B12 supplements. Patients who have had bariatric surgery should receive 1 mg of oral vitamin B12 per day indefinitely. Use of vitamin B12 in patients with elevated serum homocysteine levels and cardiovascular disease does not reduce the risk of myocardial infarction or stroke, or alter cognitive decline.
Topics: Humans; Hyperhomocysteinemia; Methylmalonic Acid; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 28925645
DOI: No ID Found -
Blood May 2017B deficiency is the leading cause of megaloblastic anemia, and although more common in the elderly, can occur at any age. Clinical disease caused by B deficiency usually... (Review)
Review
B deficiency is the leading cause of megaloblastic anemia, and although more common in the elderly, can occur at any age. Clinical disease caused by B deficiency usually connotes severe deficiency, resulting from a failure of the gastric or ileal phase of physiological B absorption, best exemplified by the autoimmune disease pernicious anemia. There are many other causes of B deficiency, which range from severe to mild. Mild deficiency usually results from failure to render food B bioavailable or from dietary inadequacy. Although rarely resulting in megaloblastic anemia, mild deficiency may be associated with neurocognitive and other consequences. B deficiency is best diagnosed using a combination of tests because none alone is completely reliable. The features of B deficiency are variable and may be atypical. Timely diagnosis is important, and treatment is gratifying. Failure to diagnose B deficiency can have dire consequences, usually neurological. This review is written from the perspective of a practicing hematologist.
Topics: Anemia, Megaloblastic; Anemia, Pernicious; Animals; Folic Acid; Humans; Intestinal Absorption; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 28360040
DOI: 10.1182/blood-2016-10-569186 -
Archives of Pathology & Laboratory... Nov 2019Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia.... (Review)
Review
CONTEXT.—
Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management.
OBJECTIVE.—
To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG.
DATA SOURCES.—
The sources of the study include a review of the pertinent literature for AG.
CONCLUSIONS.—
Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.
Topics: Anemia, Pernicious; Autoimmune Diseases; Biopsy; Chronic Disease; Diagnosis, Differential; Diagnostic Errors; Epithelium; Gastritis, Atrophic; Humans; Hyperplasia; Intrinsic Factor; Metaplasia; Stomach
PubMed: 31661309
DOI: 10.5858/arpa.2019-0345-RA -
Journal of General and Family Medicine Oct 2017Anemia is one of the most common health problems in the primary care setting. Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV)... (Review)
Review
Anemia is one of the most common health problems in the primary care setting. Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) >100 femtoliter (fL). Macrocytic anemias are generally classified into megaloblastic or nonmegaloblastic anemia. Megaloblastic anemia is caused by deficiency or impaired utilization of vitamin B12 and/or folate, whereas nonmegaloblastic macrocytic anemia is caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and by less commonly inherited disorders of DNA synthesis. Macrocytic anemias are treated with cause-specific therapies, and it is crucial to differentiate nonmegaloblastic from megaloblastic anemia. Because MDS and myeloid neoplasms commonly affect the elderly, primary care physicians may encounter more cases of macrocytic anemias in the near future, as the older population increases. When MDS is suspected along with leukocytopenia and/or thrombocytopenia with anemia, a hematology consultation may be appropriate.
PubMed: 29264027
DOI: 10.1002/jgf2.31 -
World Journal of Diabetes Jul 2021To date, metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and... (Review)
Review
To date, metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile. Indeed, metformin is the most widely used oral insulin-sensitizing agent, being prescribed to more than 100 million people worldwide, including patients with prediabetes, insulin resistance, and polycystic ovary syndrome. However, over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency. Of note, evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status. Vitamin B12 (also referred to as cobalamin) is a water-soluble vitamin that is mainly obtained from animal-sourced foods. At the cellular level, vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection. Thus, vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities (, megaloblastic anemia and formation of hypersegmented neutrophils), progressive axonal demyelination and peripheral neuropathy. Nevertheless, no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy, and vitamin B12 deficiency remains frequently unrecognized in such individuals. Therefore, in this "field of vision" article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients, which could serve as a practical guide for identifying individuals at high risk for this condition. Moreover, we discuss additional relevant topics related to this field, including: (1) The lack of consensus about the exact definition of vitamin B12 deficiency; (2) The definition of reliable biomarkers of vitamin B12 status; (3) Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis; and (4) Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency. Finally, we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency, particularly when this condition is induced by metformin.
PubMed: 34326945
DOI: 10.4239/wjd.v12.i7.916 -
Nutrients Apr 2022Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from... (Review)
Review
Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.
Topics: Anemia, Pernicious; Gastritis; Humans; Micronutrients; Precancerous Conditions; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins
PubMed: 35458234
DOI: 10.3390/nu14081672 -
Mayo Clinic Proceedings. Innovations,... Jun 2019Although cobalamin (vitamin B) deficiency was described over a century ago, it is still difficult to establish the correct diagnosis and prescribe the right treatment.... (Review)
Review
Although cobalamin (vitamin B) deficiency was described over a century ago, it is still difficult to establish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B deficiency may present with the classic megaloblastic anemia. In clinical practice, many cases of vitamin B deficiency are overlooked or sometimes even misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with vitamin B deficiency in whom the diagnosis was either based on low serum B levels, elevated biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical symptoms after the institution of parenteral vitamin B therapy. We discuss the possible clinical signs and symptoms of patients with B deficiency and the various pitfalls of diagnosis and treatment.
PubMed: 31193945
DOI: 10.1016/j.mayocpiqo.2019.03.002