CAUSES OF MEGALOBASTIC ANEMIA
B12 DEFICIENCY ã…¡ Lack of intrinsic factor necessary for absorption (pernicious anemia) and chronic proton pump inhibitor (PPI) use. Long-term metformin treatment (4 years) results in B12 deficiency in about 1 of every 14 patients treated.
-
Metformin dose > 1500 mg/day is associated with B12 deficiency. Supplementation may protect against thisdeficiency but more research is needed.
FOLIC ACID DEFICIENCY ã…¡ Dietary deficiency due to alcohol abuse, cancer, or chemotherapy such as 6-mercaptopurine (Purinethol). Other medications that can cause megloblastic anemia like anticonvulsants (valproic acid, phenytoin), folate antagonists (methotrexate), antibiotics (trimethoprim/sulfamethoxazole).
DIAGNOSIS
CBC will identify patients with macrocytic anemia. Folate and B12 levels will determine whether these are the cause of macrocytosis. If B12 is indeterminate (100-400 pg/mL), order methylmalonic acid and homocysteine levels. Elevation of both is diagnostic of B12 deficiency (homocysteine but not methylmalonic acid is also elevated in folate deficiency).
Schilling test to identify patients without intrinsic factor is not necessary since B12 can be absorbed without intrinsic factor when given in sufficient oral doses.
- In patients with symptoms suggestive of anemia, a CBC will determine whether macrocytic anemia exists.
- Order B12 and folate levels; if vitamin B12 is between 100 and 400 pg/mL, order methylmalonic acid and homocysteine.
- If both methylmalonic acid and homocysteine are elevated, or if either is elevated and folic acid is normal, diagnose B12 deficiency. If both are normal, consider other diagnoses.
TREATMENT
FOR B12 DEFICIENCY ã…¡ Oral B12 1000 mcg/day or 1000 mcg IM monthly will replete and maintain B12 levels. Oral B12 is as effective as monthly IM administration in patients with or without the intrinsic factor. This is also true in children. Oral B12 dosage started by 1000 to 2000 mcg/day for 1 to 2 weeks. The maintenance dose is 1000 mcg/day.
IM B12 dosage, initially 100 to 1000 mcg/day or every other day for 1 to 2 weeks. The maintenance dose is100 to 1000 mcg every 1 to 3 months. A toothpaste fortified with vitamin B12 increases methylmalonic acid levels in vegans.
FOR FOLATE DEFICIENCY ã…¡ Giving folic acid 1 to 5 mg daily will replete deficiency in 4 to 6 weeks.
NUTRITION ã…¡ If malnutrition is the cause, increasing foods with B12 and folic acid is appropriate. Oat-bran (5.2 g/day) can improve constipation and slow the decrease in B12 seen among frail, geriatric home residents. Foods rich in B12 include, molluscs, clams, beef liver, fortified breakfast cereals, trout, salmon, beef, haddock,and tuna. Foods rich in folic acid include, breakfast cereals fortified with folate, beef liver, cowpeas, spinach, asparagus, broccoli, avocado, fortified rice, and beans. Treatment depends on cause and it is usually lifelong.REFERENCES
-
Hannibal L, Lysne V, Bjørke-Monsen AL, Behringer S, Grünert SC, Spiekerkoetter U, Jacobsen DW, Blom HJ. Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency. Front Mol Biosci. 2016 Jun 27;3:27. Available at: https://www.frontiersin.org/articles/10.3389/fmolb.2016.00027/full
Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med. 1999 Jun 28;159(12):1289-98. Available at: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485067
Cylwik B, Chrostek L. Zaburzenia metabolizmu kwasu foliowego i homocysteiny w warunkach naduzywania alkoholu [Disturbances of folic acid and homocysteine metabolism in alcohol abuse]. Pol Merkur Lekarski. 2011 Apr;30(178):295-9. Polish. PMID: 21595178. Available at: https://pubmed.ncbi.nlm.nih.gov/21595178
Elia M. Oral or parenteral therapy for B12 deficiency. Lancet. 1998 Nov 28;352(9142):1721-2. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)79821-4/fulltext