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American Family Physician Jun 2010Anemia is defined as a hemoglobin level of less than the 5th percentile for age. Causes vary by age. Most children with anemia are asymptomatic, and the condition is... (Review)
Review
Anemia is defined as a hemoglobin level of less than the 5th percentile for age. Causes vary by age. Most children with anemia are asymptomatic, and the condition is detected on screening laboratory evaluation. Screening is recommended only for high-risk children. Anemia is classified as microcytic, normocytic, or macrocytic, based on the mean corpuscular volume. Mild microcytic anemia may be treated presumptively with oral iron therapy in children six to 36 months of age who have risk factors for iron deficiency anemia. If the anemia is severe or is unresponsive to iron therapy, the patient should be evaluated for gastrointestinal blood loss. Other tests used in the evaluation of microcytic anemia include serum iron studies, lead levels, and hemoglobin electrophoresis. Normocytic anemia may be caused by chronic disease, hemolysis, or bone marrow disorders. Workup of normocytic anemia is based on bone marrow function as determined by the reticulocyte count. If the reticulocyte count is elevated, the patient should be evaluated for blood loss or hemolysis. A low reticulocyte count suggests aplasia or a bone marrow disorder. Common tests used in the evaluation of macrocytic anemias include vitamin B12 and folate levels, and thyroid function testing. A peripheral smear can provide additional information in patients with anemia of any morphology.
Topics: Adolescent; Age Factors; Anemia; Anemia, Iron-Deficiency; Anemia, Macrocytic; Blood Transfusion; Child; Child, Preschool; Erythrocyte Count; Erythrocyte Indices; Hemoglobins; Humans; Infant; Infant, Newborn; Iron; Reticulocyte Count; Risk Factors
PubMed: 20540485
DOI: No ID Found -
American Family Physician Feb 2009Macrocytosis, generally defined as a mean corpuscular volume greater than 100 fL, is frequently encountered when a complete blood count is performed. The most common... (Review)
Review
Macrocytosis, generally defined as a mean corpuscular volume greater than 100 fL, is frequently encountered when a complete blood count is performed. The most common etiologies are alcoholism, vitamin B12 and folate deficiencies, and medications. History and physical examination, vitamin B12 level, reticulocyte count, and a peripheral smear are helpful in delineating the underlying cause of macrocytosis. When the peripheral smear indicates megaloblastic anemia (demonstrated by macro-ovalocytes and hyper-segmented neutrophils), vitamin B12 or folate deficiency is the most likely cause. When the peripheral smear is non-megaloblastic, the reticulocyte count helps differentiate between drug or alcohol toxicity and hemolysis or hemorrhage. Of other possible etiologies, hypothyroidism, liver disease, and primary bone marrow dysplasias (including myelodysplasia and myeloproliferative disorders) are some of the more common causes.
Topics: Alcohol Drinking; Algorithms; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Cell Count; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Erythrocyte Count; Erythrocyte Indices; FIGLU Test; Folic Acid Deficiency; Humans; Hypothyroidism; Liver Diseases; Myeloproliferative Disorders; Neural Tube Defects; Predictive Value of Tests; Reticulocyte Count; Risk Factors; Sensitivity and Specificity; Vitamin B 12 Deficiency
PubMed: 19202968
DOI: No ID Found -
Indian Pediatrics Sep 2022There is limited literature in children on efficacy of different routes of vitamin B12 administration for vitamin B12 deficiency macrocytic-megaloblastic anemia. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There is limited literature in children on efficacy of different routes of vitamin B12 administration for vitamin B12 deficiency macrocytic-megaloblastic anemia.
OBJECTIVE
To compare parenteral with oral vitamin B12 therapy in children with macrocytic-megaloblastic anemia.
STUDY DESIGN
Single-center, open-label randomized controlled trial.
PARTICIPANT
80 children aged 2 month-18 year with clinical and laboratory features of nutritional macrocytic anemia.
INTERVENTION
All children received an initial single parenteral dose of 1000 µg vitamin B12 followed by randomization to either parenteral or oral vitamin B12 for subsequent doses. Group A was given 1000 µg intramuscular (IM) vitamin B12 (3 doses on alternate days for those aged <10 year, five doses for age >10 year), followed by monthly 1000 µg IM for the subsequent two doses. Group B was given daily oral vitamin B12 1500 µg (500 µg in <2 years age) for three months. Folic acid and iron supple-mentation, and relevant dietary advice were given to both groups in a similar fashion.
OUTCOME
Improvement in serum vitamin B12 levels and total hemoglobin was compared three months post-treatment.
RESULT
The median(IQR) increase in serum vitamin B12 level was significantly higher in group A [600 (389,775) vs 399 (313, 606) pg/mL; P= 0.016]. The median (IQR) rise of hemoglobin was also more in group A [2.7 (0.4,4.6) vs 0.5 (-0.1,1.2) g/dL; P=0.001].
CONCLUSION
Increase in serum vitamin B12 levels and hemoglobin was better in children with nutritional macrocytic anemia receiving parenteral as compared to oral vitamin B12.
Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Child; Folic Acid; Hemoglobins; Humans; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 35642923
DOI: No ID Found -
Genetics in Medicine : Official Journal... Feb 2019Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was to...
PURPOSE
Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was to describe macrocytic erythrocytes as another common aspect of the phenotype.
METHODS
The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly.
RESULTS
Macrocytic erythrocytes occurred in 81-92% of subjects with Lesch-Nyhan disease or its neurological variants. After excluding cases with iron deficiency because it might pseudonormalize erythrocyte volumes, macrocytosis occurred in 97% of subjects. Macrocytic erythrocytes were sometimes accompanied by mild anemia, and rarely by severe anemia.
CONCLUSION
These results establish macrocytic erythrocytes as a very common aspect of the clinical phenotype of Lesch-Nyhan disease and its neurological variants. Macrocytosis is so characteristic that its absence should prompt suspicion of a secondary process, such as iron deficiency. Because macrocytosis is uncommon in unaffected children, it can also be used as a clue for early diagnosis in children with neurodevelopmental delay. Better recognition of this characteristic feature of the disorder will also help to prevent unnecessary diagnostic testing and unnecessary attempts to treat it with folate or B12 supplements.
Topics: Adolescent; Adult; Anemia, Macrocytic; Child; Child, Preschool; Humans; Infant; Lesch-Nyhan Syndrome; Longitudinal Studies; Male; Phenotype; Young Adult
PubMed: 29875418
DOI: 10.1038/s41436-018-0053-1 -
Experimental Hematology Nov 2020The discovery that the immunomodulatory imide drugs (IMiDs) possess antitumor properties revolutionized the treatment of specific types of hematological cancers. Since... (Review)
Review
The discovery that the immunomodulatory imide drugs (IMiDs) possess antitumor properties revolutionized the treatment of specific types of hematological cancers. Since then, much progress has been made in understanding why the IMiDs are so efficient in targeting the malignant clones in difficult-to-treat diseases. Despite their efficacy, IMiD resistance arises eventually. Herein we summarize the mechanisms of sensitivity and resistance to lenalidomide in del(5q) myelodysplastic syndrome and multiple myeloma, two diseases in which these drugs are at the therapeutic frontline. Understanding the molecular and cellular mechanisms underlying IMiD efficacy and resistance may allow development of specific strategies to eliminate the malignant clone in otherwise incurable diseases.
Topics: Adaptor Proteins, Signal Transducing; Anemia, Macrocytic; Angiogenesis Inhibitors; Antineoplastic Agents; Autophagy; Cell Differentiation; Chromosome Deletion; Chromosomes, Human, Pair 5; Cytokines; Disease Progression; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Ikaros Transcription Factor; Immunologic Factors; Lenalidomide; Megakaryocytes; Multiple Myeloma; Neoplasm Proteins; Neovascularization, Pathologic; Phosphoprotein Phosphatases; Ubiquitin-Protein Ligases
PubMed: 32976949
DOI: 10.1016/j.exphem.2020.09.196 -
The EMBO Journal Jul 2022Red blood cells are produced by terminal erythroid differentiation, which involves the dramatic morphological transformation of erythroblasts into enucleated...
Red blood cells are produced by terminal erythroid differentiation, which involves the dramatic morphological transformation of erythroblasts into enucleated reticulocytes. Microtubules are important for enucleation, but it is not known if the centrosome, a key microtubule-organizing center, is required as well. Mice lacking the conserved centrosome component, CDK5RAP2, are likely to have defective erythroid differentiation because they develop macrocytic anemia. Here, we show that fetal liver-derived, CDK5RAP2-deficient erythroid progenitors generate fewer and larger reticulocytes, hence recapitulating features of macrocytic anemia. In erythroblasts, but not in embryonic fibroblasts, loss of CDK5RAP2 or pharmacological depletion of centrosomes leads to highly aberrant spindle morphologies. Consistent with such cells exiting mitosis without chromosome segregation, tetraploidy is frequent in late-stage erythroblasts, thereby giving rise to fewer but larger reticulocytes than normal. Our results define a critical role for CDK5RAP2 and centrosomes in spindle formation specifically during blood production. We propose that disruption of centrosome and spindle function could contribute to the emergence of macrocytic anemias, for instance, due to nutritional deficiency or exposure to chemotherapy.
Topics: Anemia, Macrocytic; Animals; Cell Cycle Proteins; Centrosome; Chromosome Segregation; Mice; Microtubules; Mitosis; Spindle Apparatus
PubMed: 35678476
DOI: 10.15252/embj.2021108739 -
World Journal of Gastroenterology Oct 2009Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia,... (Review)
Review
Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classification (microcytic, macrocytic and normocytic) and pathogenic classification (regenerative and hypo regenerative), and integration of these classifications. Interpretation of laboratory tests is included, from the simplest (blood count, routine biochemistry) to the more specific (iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test). In the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other complementary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time.
Topics: Anemia; Anemia, Macrocytic; Erythrocyte Indices; Gastroenterology; Hemoglobins; Humans; Reticulocyte Count; Reticulocytes
PubMed: 19787825
DOI: 10.3748/wjg.15.4627 -
British Medical Journal Mar 1951
Topics: Anemia; Anemia, Macrocytic; Intestines; Tracheophyta
PubMed: 14821506
DOI: 10.1136/bmj.1.4708.677 -
Zeitschrift Fur Rheumatologie Apr 2024An adult-onset autoinflammatory syndrome caused by somatic mutations in the UBA1 gene on the X chromosome was first reported in 2020. This VEXAS syndrome (acronym for...
An adult-onset autoinflammatory syndrome caused by somatic mutations in the UBA1 gene on the X chromosome was first reported in 2020. This VEXAS syndrome (acronym for vacuoles, E1 enzyme, X‑linked, autoinflammatory, somatic) is characterized by an overlap of rheumatic inflammatory diseases with separate hematologic abnormalities. A substantial number of affected patients suffer from treatment refractory relapsing polychondritis and nearly always show signs of macrocytic anemia. This case report illustrates the diagnostic key points to recognizing patients with VEXAS syndrome.
Topics: Adult; Humans; Anemia, Macrocytic; Autoimmune Diseases; Polychondritis, Relapsing; Myelodysplastic Syndromes; Rheumatic Diseases; Mutation; Skin Diseases, Genetic
PubMed: 36735069
DOI: 10.1007/s00393-023-01318-5 -
American Journal of Human Genetics Nov 2013We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic...
We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia.
Topics: Adolescent; Anemia, Macrocytic; Animals; Child; Erythropoiesis; Exome; Female; Gene Knockdown Techniques; Humans; Membrane Proteins; Mitochondrial Diseases; Mitochondrial Proteins; Mutation; Zebrafish
PubMed: 24119684
DOI: 10.1016/j.ajhg.2013.09.011