eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Megaloblastic Anemia: Treatment & Medication

Author: Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Contributor Information and Disclosures

Updated: Aug 26, 2009

Treatment

Medical Care

Most patients with megaloblastosis are treated with cobalamin and folate therapy to treat deficiencies in these substances. Transfusion therapy should be restricted to patients with severe, uncompensated, and life-threatening anemia. Because megaloblastic anemias usually develop gradually, most patients have adjusted to low Hgb levels and do not require transfusions.

  • Cobalamin (1000 mcg) should be given parenterally daily for 2 weeks, then weekly until the hematocrit value is normal, and then monthly for life. This dose is large, but it may be required in some patients. Patients with neurological complications should receive cobalamin at 1000 mcg (more in some cases) every day for 2 weeks, then every 2 weeks for 6 months, and monthly for life.
    • Oral cobalamin (1000 mcg) can be administered to patients with hemophilia (to avoid intramuscular injections) and to patients with severe malnutrition or those who have abnormalities in the terminal ileum. Doses and schedules differ in recent publications. However, oral dosages should be monitored for desired response, since absorption can be variable and may be insufficient in some patients.
    • It may be practical to initially administer parenteral cobalamin to a patient with vitamin B-12 deficiency and then to continue treatment with oral cobalamin. Oral cobalamin is cost effective and better accepted by patients.
  • Folate (1-5 mg) should be administered orally. If this is difficult, comparable doses can be administered parenterally.7,8
  • Therapeutic options when the etiology of megaloblastosis is uncertain include therapeutic doses of both cobalamin and folate after serum level measurements for cobalamin and folate levels, bone marrow, and other studies have been initiated. The Schilling test is not affected by previous therapy. Another option is to administer a trial of a physiological dose of folate. Cobalamin deficiency does not respond to daily folate doses of 100-400 mcg (physiological dose), but this dose results in complete response in patients with folate deficiency. Under no circumstances should therapeutic doses of folate (1-5 mg/d) be administered without cobalamin. The reason is that folate therapy corrects the anemia, but folate does not correct a cobalamin-induced neurological disorder and thus results in the progression of neuropsychiatric complications.
  • Prophylactic folate therapy (1 mg/d) should be administered during pregnancy and the perinatal period to meet the increased demand for folate by the fetus and during lactation. Folate should also be given daily to patients with chronic hemolysis. Folate therapy is currently recommended for individuals with high levels of homocysteine who have a propensity for thromboembolic disease to prevent this complication.9 Multivitamins that contain folate have been recommended for elderly persons.
    • Fortification of foods with folic acid has been recommended to prevent hyperhomocysteinemia-related thrombosis, folate deficiency–related neoplasia, and pregnancy-related fetal abnormalities.
    • However, opponents to the fortification plan are concerned that folate-fortified foods given to patients with unrecognized cobalamin deficiencies will increase the frequency of cobalamin-induced neuropsychiatric disorders.
  • Cobalamin therapy can be beneficial for patients with borderline cobalamin deficiency or in patients who present with only neuropsychiatric disorders. The role of minimal cobalamin deficiency in patients with borderline neuropsychiatric dysfunction has recently been recognized because of more sensitive tests and a greater awareness of this potential problem. One cause of borderline cobalamin deficiency is food-cobalamin malabsorption, described in the protein-bound absorption test discussion. Treatment with 50 mcg of oral cyanocobalamin daily can restore cobalamin stores in these patients.
  • Blind loop syndrome should be treated with antibiotics.
  • Patients with TCII deficiency may require higher doses of cobalamin.
  • Tropical sprue should be treated with cobalamin and folate.
  • Acute megaloblastic anemias due to nitrous oxide exposure can be treated with folate (5 mg/d) and cobalamin (1 mg IM).
  • Fish tapeworm infection, pancreatitis, Zollinger-Ellison syndrome, and inborn errors should be treated with appropriate measures.

Consultations

  • A hematologist should be consulted if the cause of the macrocytosis is not clear, if a patient does not respond adequately to therapy, and if neurological complications occur.
  • A neurologist should be consulted for patients with potential neurological complications of cobalamin and folate deficiencies.
  • A gastroenterologist should be consulted for the treatment of blind loop syndromes. In the case of diagnosed pernicious anemia, upper endoscopy should be performed to help rule out atrophic gastritis and because these patients are at greater risk of developing gastric carcinoma.
  • A pediatrician with expertise in inborn errors should be consulted to help treat children with inborn errors.

Diet

  • Patients should include rich sources of folate in their diets. Examples include asparagus, broccoli, spinach, lettuce, lemons, bananas, melons, liver, and mushrooms.
  • To prevent loss of folate, foods should not be cooked excessively, especially in large amounts of water.
  • To prevent cobalamin deficiency, patients who prefer vegetarian diets should include dairy products and eggs in their meals.

Medication

The goals of pharmacotherapy are to correct possible vitamin deficiencies, to prevent complications, and to reduce morbidity.

Vitamins

Cyanocobalamin (vitamin B-12) and folic acid are used to treat megaloblastic and macrocytic anemias secondary to deficiency. Both vitamin B-12 and folic acid are required for synthesis of purine nucleotides and metabolism of some amino acids. Each is essential for normal growth and replication. Deficiency of either cyanocobalamin or folic acid results in defective DNA synthesis and cellular maturation abnormalities. Consequences of deficiency are most evident in tissues with high cell turnover rates (eg, hematopoietic system).


Cyanocobalamin (Cyomin, Crysti 1000, Crystamine)

Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B-12 in humans. Microbes synthesize vitamin B-12, but humans and plants do not. Vitamin B-12 deficiency may result from IF deficiency (PA), partial or total gastrectomy, or diseases of the distal ileum.

Adult

Severe anemia: 1000 mcg/d IM for 2 wk, then qwk until HCT is normal, then monthly for life; alternatively, 1000 mcg/d PO when IM contraindicated
Neurological complications: 1000 mcg/d (in some instances higher doses) IM for 2 wk initially, followed by q2wk for 6 mo, then monthly for life

Pediatric

100 mcg/d IM for 2 wk, then qwk until HCT is normal, then, 60 mcg/d IM monthly; alternatively, up to 1000 mcg/d PO when IM contraindicated

Documented hypersensitivity; hereditary optic nerve atrophy

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in pregnancy when dose exceeds RDA; severe hypokalemia may result in vitamin B-12 megaloblastic anemia (may be fatal) due to increased cellular potassium requirements when anemia corrects


Folic acid (Folvite)

Essential cofactor for enzymes used in production of RBCs.

Adult

1-5 mg/d PO/IV/IM/SC; if cobalamin deficiency has not been excluded, folate must be administered with cyanocobalamin

Pediatric

<6 months: No established
6 months-11 years: 1 mg/d PO/IV/IM/SC initially, then 0.1-0.4 mg/d maintenance dose
>11 years: 1 mg/d PO/IV/IM/SC qd initially, then 0.5 mg/d maintenance dose; must be administered with cyanocobalamin

May decrease serum phenytoin levels; coadministration of dihydrofolate reductase inhibitors (eg, methotrexate, cotrimoxazole) may interfere with folic acid utilization

Pregnancy

A - Safe in pregnancy

Precautions

Caution in pregnancy if dose exceeds RDA; benzyl alcohol may be contained in some products as a preservative (associated with a fatal gasping syndrome in premature infants); resistance to treatment may occur in patients with alcoholism and deficiencies of other vitamins

More on Megaloblastic Anemia

Overview: Megaloblastic Anemia
Differential Diagnoses & Workup: Megaloblastic Anemia
Treatment & Medication: Megaloblastic Anemia
Follow-up: Megaloblastic Anemia
References
Further Reading
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References

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  2. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. May 5 2009;150(9):626-31. [Medline].

  3. Wang YH, Yan F, Zhang WB, Ye G, Zheng YY, Zhang XH, et al. An investigation of vitamin B12 deficiency in elderly inpatients in neurology department. Neurosci Bull. Aug 2009;25(4):209-15. [Medline].

  4. Dali-Youcef N, Andres E. An update on cobalamin deficiency in adults. QJM. Jan 2009;102(1):17-28. [Medline].

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  8. Lawrence MA, Chai W, Kara R, Rosenberg IH, Scott J, Tedstone A. Examination of selected national policies towards mandatory folic acid fortification. Nutr Rev. May 2009;67 Suppl 1:S73-8. [Medline].

  9. Varela-Moreiras G, Murphy MM, Scott JM. Cobalamin, folic acid, and homocysteine. Nutr Rev. May 2009;67 Suppl 1:S69-72. [Medline].

  10. Babior BM. The megaloblastic anemias. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. Williams Hematology. 5th ed. New York, NY: McGraw-Hill; 1995:. 471-89.

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Further Reading

Related eMedicine Topics

Clinical Trials

National Guideline Clearinghouse

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Keywords

megaloblastic anemia, megaloblastosis, anemia, cobalamin deficiency, vitamin B-12 deficiency, folate deficiency, pernicious anemia, PA, homocysteine, cobalamin neuropathy, pregnancy, neural tube defects, anemia and the elderly, blood disorder, ineffective erythropoiesis, food-cobalamin malabsorption,

gastrectomy, Zollinger-Ellison syndrome, ZES, ileal resection, regional ileitis, intestinal lymphoma, Diphyllobothrium latum, D latum, fish tapeworm, blind loop syndrome, nitrous oxide exposure, NO exposure, surgical intestinal resection, amyloidosis, Whipple disease, scleroderma, psoriasis, exfoliative dermatitis, drug reactions, chemotherapy, neurological impairment

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Contributor Information and Disclosures

Author

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Thomas H Davis, MD, FACP, Associate Professor, Fellowship Program Director, Department of Internal Medicine, Section of Hematology/Oncology, Dartmouth Medical School
Thomas H Davis, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Education, American College of Physicians, New Hampshire Medical Society, Phi Beta Kappa, and Society of University Urologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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