What is the initial investigation for macrocytic anemia?
Peripheral blood smear (PBS) to look for megaloblastic changes (hypersegmented neutrophils)
What are the possible findings of a PBS in macrocytic anemia?
Hypersegmented neutrophils (> 5 lobes): megaloblastic anemia
No hypersegmented neutrophils: nonmegaloblastic anemia
Green: hyperplasia erytrhoid precursors
Red: Neutrophils (larger, hypersegmented nuclei)
Yellow: Erythrocyte precursors (contain basopholic nulclear remnants, so-called Howell-Jolly bodies (arrows))
—> Megaloblastic anemia
Hypersegmented neutrophils
What should be obtained in all patients with megaloblastic changes on PBS?
Vitamin B12 and folate levels
—> Vitamin B12 levels < 200 pg/mL: vitamin B12 deficiency
—>Folate < 2 ng/mL: folate deficiency
When should serum homocysteine and methylmalonic acid levels be obtained?
obtain in patients with borderline serum vitamin B12 and/or folate levels (Vitamin B12 200–300 pg/mL and/or folate < 2–4 ng/mL)
How would a folic acid deficiency be diagnosed?
Normal methylmalonic acid but ↑ homocysteine levels
How would a Vitamin B12 deficiency be diagnosed?
↑ Methylmalonic acid, normal/↑ homocysteine: vitamin B12 deficiency
List reasons to consider a bone marrow biopsy.
Normal vitamin B12 and folate levels
Normal methylmalonic acid and homocysteine levels
Unexplained thrombocytopenia, leukocytopenia, or pancytopenia
Numerous immature forms of blood cells on CBC and/or PBS
What can be an additional evaluation?
consider urine orotic acid levels if orotic aciduria is suspected (extremely rare)
Orotic aciduria is extremely uncommon and not part of the usual workup of macrocytic anemia. Suspect orotic aciduria in infants or young children with megaloblastic anemia unresponsive to vitamin B12 and folate supplementation; see clinical features of orotic aciduria for further details.
Summarize how serum methylmalonic acid levels and homocysteine levels behave in both folic acid deficiency and vit. B12 deficiency.
Serum methylmalonic acid levels are normal in folic acid deficiency and elevated in vitamin B12 deficiency. Serum homocysteine levels are elevated in both.
What should be the initial test in nonmegaloblastic macrocytic anemia?
Reticulocyte count —> Obtain in all patients with nonmegaloblastic macrocytic anemia to evaluate bone marrow response
What should be futher tests if there is a normal/low reticulocyte count (< 2%)?
Obtain a detailed drug and alcohol use history.
Consider TSH, hepatic panel.
Why should a detailed drug/alcohol history be obtained in nonmegaloblastic macrocytic anemia?
Drug/alcohol-induced macrocytosis is one of the most common causes of macrocytic anemia. Medications that can cause macrocytosis include hydroxyurea, 5-fluorouracil, methotrexate, and trimethoprim.
What should be futher tests if there is a high reticulocyte count (> 2%)?
Reassess history for evidence of acute or chronic blood loss.
Check hemolysis labs: ↓ haptoglobin, ↑ LDH, ↑ unconjugated bilirubin suggest a hemolytic anemia
What should be considered in nonmegaloblastic macrocytic anemia if reticulocyte count and metabolic panels are normal and there is no history of drug/alcohol use?
Hemoglobin electrophoresis: ↑ HbF level indicates Diamond-Blackfan anemia
Bone marrow biopsy
Hypercellular marrow with dysplasia of all three cell lines: myelodysplastic syndrome
Hypocellular fat-filled marrow : aplastic anemia
Absent or sparse erythroid precursors: pure red cell aplasia
What are the most common causes of macrocytosis?
The most common causes of macrocytosis are chronic alcohol consumption, vitamin B12 and/or folate deficiency, and certain medications.
Last changed2 years ago
