Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Megaloblastic Anemia Testing Algorithm
Clinical Background
Megaloblastic anemias are a group of macrocytic anemias in which the bone marrow shows megaloblastic erythropoieses.
Epidemiology
- Prevalence- macrocytosis occurs in 2-4% of the population
- Age - more common in older adults
Etiology
- Cobalamin deficiency (B12)
- Malabsorption
- Achlorhydria
- Most common in the elderly and patients on acid suppression
- Postgastrectomy
- Intestinal stasis due to anatomic lesions
- Ileal abnormalities
- Tropical sprue
- Inherited disorders of B12
- Folic acid deficiency
- Malabsorption, inadequate intake
- Drugs
- Metabolic disorders
- Inherited disorders of folate
- Combined deficiencies of folic acid and cobalamin are not uncommon
Clinical Presentation
- Symptoms
- Often based on the presence of anemia
- Pale skin, anorexia, sore tongue, numbness, paresthesias
- >50% present without anemia
- Pernicious anemia - most common cause of B12 deficiency
- Caused by absence of intrinsic factor (IF)
- Often caused by autoimmune destruction of parietal cells (PCA)
- 80% have PCA, 50% or greater have IF blocking antibodies
- Most common in patients of northern European descent
- Increased incidence in patients with other autoimmune diseases such as Graves, vitiligo, hypoparathyroidism, Addison disease, Hashimoto thyroiditis
Treatment
- Folate replacement is oral
- B12 replacement is parenteral or intranasal
- In pernicious anemia - lifelong replacement is necessary
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Megaloblastic Anemia Testing Algorithm
Diagnosis
Diagnosis
- Indications for Testing - anemia with macrocytosis
- Laboratory testing
- CBC
- Blood smear with macro ovalocytes, anisocytosis, hypersegmented nuclei in white blood cells
- Reticulocyte count - usually low
- B12 and folate levels - to differentiate between single and combined defect
- May also use serum RBC folate
- May consider methylmalonic acid (MMA) or homocysteine levels with B12 testing to increase sensitivity
- If B12 levels are low - consider evaluation for pernicious anemia
- PCA and intrinsic factor blocking antibody testing (see algorithm)
- PCA is not as helpful as intrinsic factor blocking because of lack of specificity
- Serum gastrin levels may be useful
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Megaloblastic Anemia Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: CBC with Platelet Count
|
| ARUP #: 0040002 |
| Methodology: Automated Cell Count
|
| Use: Screen for anemia |
| Test name: Vitamin B12 & Folate
|
| ARUP #: 0070160 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: First line test for differentiating cause of megaloblastic anemia |
| Limitations: |
| Follow-up:
|
| Test name: Vitamin B12 with Reflex to Methylmalonic Acid (MMA), Serum Quantitative
|
| ARUP #: 0055662 |
| Methodology: Chemiluminescent Immunoassay/Tandem Mass Spectrometry
|
| Use: Useful test in work up of megaloblastic anemia |
| Limitations: Renal failure may increase serum MMA concentrations in patients who do not have vitamin B12 deficiency |
| Test name: Folate, RBC
|
| ARUP #: 0070385 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Include in a differential work-up of patients with megaloblastic anemia |
| Limitations: |
| Follow-up:
|
| Test name: Intrinsic Factor Blocking Antibody
|
| ARUP #: 0070210 |
| Methodology: Enzyme-Linked Immunosorbent Assay
|
| Use: Include in a differential work-up of patients with megaloblastic anemia and suspicion of pernicious anemia |
| Test name: Parietal Cell Antibody, IgG
|
| ARUP #: 0050596 |
| Methodology: Indirect Fluorescent Antibody
|
| Use: Include in a differential work-up of patients with megaloblastic anemia and suspicion of pernicious anemia |
| Limitations: Although 93% of patients with pernicious anemia will be positive for parietal cell antibody (PCA), the fact that such antibodies are found with increased frequency in unaffected family members, as well as in patients with other autoimmune diseases, suggest these antibodies do not cause disease by themselves |
| Test name: Gastrin
|
| ARUP #: 0070075 |
| Methodology: Radioimmunoassay
|
| Use: Include in a differential work-up of patients with megaloblastic anemia and suspicion of pernicious anemia in the face of negative antibody tests |
Additional Tests Available
| Test name: Methylmalonic Acid (MMA), Serum Quantitative
|
| ARUP #: 0099431 |
| Methodology: Tandem Mass Spectrometry
|
| Comments: Preferred test is B12 reflex to MMA |
| Test name: Vitamin B12
|
| ARUP #: 0070150 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: Preferred test is B12 reflex to MMA |
| Test name: Folate, Serum
|
| ARUP #: 0070070 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: Preferred test is Vitamin B12 & Folate panel |
| Test name: Vitamin B12 Binding Capacity
|
| ARUP #: 0070260 |
| Methodology: Radioimmunoassay
|
| Comments: |
| Test name: Homocysteine, Total
|
| ARUP #: 0099869 |
| Methodology: Enzymatic
|
| Comments: Confirm functional deficiency of vitamin B12 or folateFalse elevations of plasma or serum homocysteine may occur if the plasma or serum is not promptly separated from the cells at the time of collection |
References
General References
Allen LH. Folate and vitamin B12 status in the Americas. Nutr Rev.
2004;
62(
6 Pt 2):
S29-S33.
Andres E, Federici L, Affenberger S, Vidal-Alaball J, Loukili NH, Zimmer J, Kaltenbach G. B12 deficiency: a look beyond pernicious anemia. J Fam Pract.
2007;
56(
7):
537-542.
Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res.
2006;
4(
3):
236-241.
Devalia V. Diagnosing vitamin B-12 deficiency on the basis of serum B-12 assay. BMJ.
2006;
333(
7564):
385-386.
Galloway M, Hamilton M. Macrocytosis: pitfalls in testing and summary of guidance. BMJ.
2007;
335(
7625):
884-886.
Toh BH, Alderuccio F. Pernicious anaemia. Autoimmunity.
2004;
37(
4):
357-361.
Wickramasinghe SN. Diagnosis of megaloblastic anaemias. Blood Rev.
2006;
20(
6):
299-318.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Miller JW, Garrod MG, Rockwood AL, Kushnir MM, Allen LH, Haan MN, Green R. Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency. Clin Chem.
2006;
52(
2):
278-285.
Owen WE, Roberts WL. Comparison of five automated serum and whole blood folate assays. Am J Clin Pathol.
2003;
120(
1):
121-126.
Medical Reviewers
Frank, Elizabeth L. , Ph.D. Medical Director, Analytic Biochemistry and Calculi at ARUP Laboratories; Associate Professor, Clinical Pathology, University of Utah
Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah
Litwin, Christine, M.D. Medical Director, Immunology at ARUP Laboratories; Professor, Clinical Pathology, University of Utah
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Comprehensive Review: September 2008
Last Update: September 2008
