Megaloblastic anemia
Megaloblastic anemia
Updated: 7/17/2024
© Jun Wang, MD, PhD
General features
- Heterogeneous group
- Macrocytic anemia with an arrest in nuclear maturation
- Characterized by presence of megaloblasts: large nucleated RBC precursors
Etiology
- Vitamin B12 deficiency
o Gastric abnormalities
§ Gastrectomy/bariatric surgery
§ Gastritis, include autoimmune gastritis
o Small bowel disease
§ Malabsorption, Celiac disease, inflammatory bowel disease
§ Ileal resection or bypass, blind loop
§ Bacterial overgrowth, fish tapeworm
o Pancreatitis: Pancreatic insufficiency
o Diet: Breastfed infant of a VB12 deficiet mother, vegan diet, lack animal protein during pregnancy/lactation, etc
o Medication impairing VB12 absorption or metabolism
o Inherited transcobalamin II deficiency
- Folate deficiency
o Nutritional deficiency
§ Inadequate dietary intake
§ Chronic excessive alcohol use
§ Consumption of overcooked foods
§ Reduced intake of green leafy vegetables
o Malabsorption disorders: Celiac disease, short bowel syndrome, etc
o Drugs: methotrexate, trimethoprim, ethanol, phenytoin
o Increased requirements
§ Pregnancy, lactation
§ Chronic hemolysis
§ Exfoliative dermatitis or severe eczema
§ Other conditions with high cellular turnover
- Copper deficiency
- Medications that interfere with DNA synthesis, e.g. chemotherapy (5FU), antiretroviral (AZT), antimetabolite (MTX), etc
Pernicious anemia
- VB12 deficiency secondary to autoimmune gastritis
- Resulted from impaired intrinsic factor production by parietal cells, or abnormal intrinsic factor function
- Three types of autoantibodies
o Type I: blocks binding of B12 to IF (seen in 75%)
o Type II: prevent binding of IF-B12 complex ileal receptor
o Type III: against parietal cell proton pump, causing damage of parietal cells
- Patients may have history of other autoimmune diseases,
- Risk for gastric adenocarcinoma
Pathogenesis
- VB12 needed for production of thymidine
- Folate needed for production of purine base and thymidine
- Purine and thymidine needed for DNA synthesis
Key clinical findings
- Common to both B12 and Folate deficiency
o Megaloblastic anemia
o Fatigue, weight loss, fever, jaundice, decreased appetite, diarrhea, sore tongue, and fundal hemorrhages in severe cases
- More commonly vitamin B12 deficiency
o Densory parasthesias
o Motor neuropathy
o Spinal cord demyelination
o Dementia
- More commonly pernicious anemia
o Family or personal history of vitiligo
o Autoimmune thyroid disease: Hashimoto thyroiditis, Grave disease
o Other autoinflammatory disease
Key Laboratory and pathological findings
- CBC
o Low Hb, reticulocytes
o High MCV (>100 fl)
o Elevated RDW
o Macro-ovalocytosis, hypersegmented neutrophils
o Mild leukopenia and/or thrombocytopenia
- Reduce serum VB12 and/or folate
- VB12 deficiency: Elevated methylmalonic acid [MMA] and homocysteine
- Folate deficiency: Normal methylmalonic acid [MMA] and elevated homocysteine
- Autoantibodies to intrinsic factor
- Bone marrow: usually not indicated, help ruling out Myelodysplastic syndrome (MDS) and assess iron stores
Management
- Treatment focus on causes
- Favorable prognosis if the etiology identified and appropriate treatment instituted
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