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Megaloblastic Anemia Treatment & Management

  • Author: Paul Schick, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Apr 06, 2014

Approach Considerations

Once drug-induced megaloblastic changes and myelodysplasia-related megaloblastosis have been ruled out, most patients are treated with cobalamin or folate. Since megaloblastic anemias usually develop gradually, many patients adjust to low hemoglobin levels and do not require transfusions. Transfusion therapy should be restricted to patients with severe, uncompensated, and life-threatening anemia.

Go to Anemia, Chronic Anemia, Megaloblastic Anemia, Myelophthisic Anemia, Hemolytic Anemia, and Sideroblastic Anemias for complete information on these topics.


Cobalamin Therapy

Cobalamin (1000 µg) should be given intramuscularly daily for 2 weeks, then weekly until the hematocrit value is normal, and then monthly for life. A dose of 1000 µg is large, but it may be required in some patients. The reader should be aware that several other protocols for cobalamin therapy have been recommended. It is important to emphasize that patients with mental and neurological impairment due to cobalamin deficiency should be treated more aggressively.

Oral cobalamin (1000-2000 µg) also can be administered. A wide range of doses and schedules have been recommended. Therefore, oral dosages should be monitored for the desired response since absorption can be variable and may be insufficient in some patients. Note the following[12] :

  • Oral cobalamin is indicated in patients with hemophilia to avoid intramuscular injections and bleeding.
  • Intramuscular cobalamin and not oral cobalamin should be used to treat patients with cobalamin-related neurological disorders.
  • One advantage of parenteral over oral cobalamin is that all abnormalities in cobalamin absorption are bypassed.
  • It may be practical to initially administer parenteral cobalamin and then to continue treatment with oral cobalamin. Oral cobalamin is less expensive and is better tolerated by patients.

Patients who have undergone either a total or partial gastrectomy should be started on replacement therapy after the surgery to prevent the development of megaloblastosis.


Folate Therapy

Folate (3-5 mg) should be administered orally. If this is difficult, comparable doses can be administered parenterally.[13, 14]

Folate should be administered prophylactically during pregnancy, lactation, and the perinatal period. Folate is also indicated in patients with chronic hemolytic anemias, psoriasis and exfoliative dermatitis, and during extensive renal dialysis. Folate therapy has been recommended in patients with hyperhomocysteinemia who are at risk for thromboembolic complications.[15]

Fortification of foods and folic acid supplements have been recommended to reduce the risk of pancreatic, cervical, and colon cancers. Folic acid supplements are indicated in end-stage renal disease. Folate supplementation is indicated in elderly persons. However, opponents of fortification and supplementation are concerned that giving folate-fortified foods to patients with unrecognized cobalamin deficiencies will increase the frequency of cobalamin-induced neuropsychiatric disorders.

The dosage and protocol for folic acid therapy and supplementation in the various disorders mentioned above are summarized in a communication from the Mayo Clinic.[16]



Folate therapy should not be instituted in a patient with megaloblastic anemia if cobalamin deficiency has not been definitively ruled out. The danger is that folic acid will improve the anemia but not the neurological complications of cobalamin deficiency, and the neurological disorder will worsen. Both cobalamin and folate should be initiated if cobalamin deficiency has not been ruled out.


Monitoring Response to Therapy

Although patients may feel better as soon as therapy is started, monitoring the improvements with blood counts and clinical chemistry tests must be performed.

Elevated levels of lactate dehydrogenase (LDH) and indirect bilirubin should fall rapidly. A prolonged elevation of the LDH level indicates a failure of therapy, development of iron deficiency, or an error in diagnosis.

Reticulocytosis should be evident within 3-5 days and peaks in 4-10 days. Leukocyte and platelets counts are usually restored to normal within days after therapy has been started, but hypersegmented neutrophils may persist for 10-14 days.

The hemoglobin should rise approximately 1 g/dL each week. This rise is valuable for monitoring a complete response. If the hemoglobin does not rise appropriately and is not normal within 2 months, other causes of anemia, such as iron deficiency, should be considered.

Serum potassium levels can fall during therapy for severe cobalamin or folate deficiency and can lead to sudden death. Therefore, potassium should be monitored and supplements may be indicated.

Iron deficiency can occur in the course of treatment due to the consumption of iron stores for RBC production. The development of iron deficiency can impede the response to cobalamin or folate therapy. Iron therapy may be indicated.


Treatment of Other Related Conditions

Other related conditions, if present, should be addressed as follows:

  • Blind loop syndrome should be treated with antibiotics.
  • Patients with transcobalamin II (TCII) deficiency may require higher doses of cobalamin.
  • Tropical sprue should be treated with both cobalamin and folate.
  • Acute megaloblastic anemias due to nitrous oxide exposure can be treated with folate and cobalamin.
  • Fish tapeworm infection, pancreatitis, Zollinger-Ellison syndrome, and inborn errors should be treated with appropriate measures.

Dietary Measures

Patients with folate or cobalamin deficiency should receive dietary education on the choice of foods and instructions on how to prepare foods.

Patients should have diets rich with folic acid. Examples of such foods include asparagus, broccoli, spinach, lettuce, lemons, bananas, melons, liver, and mushrooms. To prevent loss of folate, foods should not be cooked excessively and should not be diluted in large amounts of water. To prevent cobalamin deficiency, vegetarians should include dairy products and eggs in their meals. Patients should know that goat milk contains little folate.



A hematologist should be consulted to assist with the diagnosis and management of patients with megaloblastic anemias.

A neurologist should be consulted for patients with potential neurological complications of cobalamin and folate deficiencies.

A gastroenterologist should be consulted since an endoscopy may be indicated to rule out atrophic gastritis and to evaluate patients for gastric carcinoma with periodic endoscopies.

A pediatrician with expertise in inborn errors should be consulted to help treat children with hereditary megaloblastosis.


Long-Term Monitoring

Patients should be monitored for recurrence of megaloblastosis by periodically testing for hemoglobin levels and, if necessary, LDH and indirect bilirubin levels.

Patients should periodically be screened for gastric cancer by endoscopy.

Contributor Information and Disclosures

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Thomas H Davis, MD, FACP Associate Professor, Fellowship Program Director, Department of Internal Medicine, Section of Hematology/Oncology, Geisel School of Medicine at Dartmouth

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, Society of University Urologists

Disclosure: Nothing to disclose.

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Megaloblastic anemia. View of red blood cells
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