Article Figures & Data
Figures
- Figure 1
A, B: Bone marrow aspirate smears showing severe megaloblastic changes: nuclear-cytoplasmic dyssynchrony, binucleation, nuclear irregularity, and basophilic stippling in erythroid lineage cells, and also hypersegmentation, nuclear-cytoplasmic dyssynchrony, and giant metamyelocytes or band forms in granulocytes (Wright-Giemsa, × 1, 000). C: Bone marrow core biopsy showing hypercellularity, erythroid hyperplasia, left shift in maturation, and small dysplastic megakaryocytes (arrow) (hematoxylin and eosin, × 400). D: Small dysplastic megakaryocytes highlighted by CD61 immunohistochemistry on the core biopsy. E, F: Increased ring sideroblasts in iron stain on the aspirate smears.
- Figure 2
A, B: Two hypersegmented neutrophils (> 6 nuclear lobes) in a peripheral blood smear (Wright-Giemsa, × 1, 000).
Tables
Vitamin B12 deficiency Folate deficiency Etiology Lack of intrinsic factor: pernicious anemia
Malabsorption: celiac disease, prior gastric or ileal surgery
Dietary deficiency less commonDietary deficiency: alcoholism, countries without food fortification
Malabsorption: developed countries
Increased demand: pregnancy, hemolytic anemia, eczemaClinical presentation Hematologic findings: cytopenias
Neuropsychiatric symptoms: paresthesias, decreased proprioception and vibratory sense, dementia, confusionHematologic findings: cytopenias Evaluation Clinical history and physical examination: symptoms secondary to anemia and hemolysis, neurologic symptoms
Laboratory testing: serum vitamin B12, methylmalonic acid, homocysteine, antiparietal cell and anti-intrinsic factor antibodies, serum gastrin
Gastric biopsy for suspected pernicious anemiaClinical history and physical examination: similar to vitamin В12 deficiency, except no neurologic symptoms
Laboratory testing: serum folate, red blood cell folate, methylmalonic acid, homocysteineDifferential diagnosis Other macrocytic anemias without megaloblastic features: liver disease, thyroid dysfunction, alcohol abuse
Myelodysplastic syndrome, acute myeloid leukemia
Nitrous oxide exposure
Medication effectOther macrocytic anemias without megaloblastic features: liver disease, thyroid dysfunction, alcohol abuse
Myelodysplastic syndrome, acute myeloid leukemia
Medication effectTreatment Parenteral vitamin В12 1-2 times per week until symptoms improve, then monthly
High-dose oral vitamin B12 dailyOral folate daily Monitoring and follow-up Clinical follow-up for improvement of neurologic symptoms
Monitor hematologic response: complete blood cell count
Pernicious anemia: consider monitoring methylmalonic acidMonitor hematologic response: complete blood cell count Common causes (related to malabsorption) Autoimmune gastritis (pernicious anemia) Celiac disease Inflammatory bowel disease Surgical gastrectomy, gastric bypass, ileal resection Less common causes Nutritional (strict vegans, breastfed infants of mothers with vitamin B12 deficiency) Nitrous oxide abuse Diphyllobothrium latum infection Pancreatic insufficiency Drug effect (metformin, proton pump inhibitors) Inherited disorders affecting intrinsic factor or the cubam receptor Rare inherited disorder (eg, methylmalonic acidemia, transcobalamin II deficiency) Information from references 4, 5, and 7.
Formulation Dose Cost per month Vitamin B12 Intramuscular injection 1, 000 μg/mL, single vial of 1 mL $5-$15 Oral 1, 000 μg/pill, 30 pills per month $2-$5 Nasal spray 500 μg/spray, single spray per day, carton of 4 $500-$640 Sublingual lozenges 3, 000 μg/lozenge, single lozenge per day, ~ 30 lozenges per month $5 Folic acid 1 mg/pill, 30 pills per month $3-$5 ↵a The dose and cost are adapted from GoodRx.com.
