Professional Documents
Culture Documents
Common Forms
of Anemia
Diagnosis and management in clinical practice.
By Jonathan Prousky, BPHE, BSc, MSc, ND
Table 2. Common Causes of Vitamin B-12 Deficiency and Associated Clinical Manifestations
(Adapted from: OH 2003)
Macrocytic Anemia in the serum and/or red blood cells when evaluating
When you have identified a macrocytic anemia, the macrocytic anemia (Barkin 1998, OH 2003), this appears
next step is to perform serum cobalamin (vitamin B-12) to be unnecessary. Folate deficiency is rarely found
testing (Barkin 1998). Table 2 highlights common causes when evaluating macrocytosis with or without anemia
of vitamin B-12 deficiency and its associated clinical (Robinson 2001). Empiric folic acid supplementation
manifestations. In terms of interpreting serum cobalamin is recommended to replace laboratory testing to
results, I have adapted a published approach to working effectively treat undiagnosed cases (Robinson 2001).
up patients with vitamin B-12 deficiency (OH 2003) to
current vitamin B-12 deficiency values obtained from Once vitamin B-12 deficiency has been identified or
several medical laboratories in Ontario. If the serum when deficiency of folic acid is suspected, it is essential
cobalamin result is below 110pmol/L (150pg/ml), then to thoroughly investigate all potential underlying causes.
the patient has vitamin B-12 deficiency and the diagnosis Begin by excluding inadequate intake due to vegetarianism,
would need to be changed to megaloblastic anemia. If the alcoholism or some other factor. Autoimmune gastritis and
serum cobalamin result is between 110 and 295pmol/L pernicious anemia should be considered as well. According
(150-400pg/ml), further testing is still required to rule out to “Consensus Guidelines on Anti-Intrinsic Factor
vitamin B-12 deficiency. At this point, urine methylmalonic Antibody Testing” (2007), clinicians need to requisition
acid testing should be done since it can identify metabolic both anti-parietal cell antibody and anti-intrinsic factor
(or tissue) vitamin B-12 deficiency when serum levels antibody testing when evaluating for these conditions.
are considered normal or in the possible deficient range If both tests are positive or if only the anti-intrins ic
(Donaldson 1987, Matchar 2000). If serum cobalamin factor antibody test is positive, the patient’s diagnosis
levels come back above 295pmol/L (>400pg/ml), the would be pernicious anemia. If only the anti-parietal cell
patient should not be considered as having vitamin B-12 antibody test is positive, the patient’s diagnosis would be
deficiency in the classical sense. This can be debated since autoimmune gastritis. Another important rule-out would be
there is published evidence of vitamin B-12 deficiency tissue transglutaminase antibodies as a first-line screening
in the cerebrospinal fluid among patients with normal test for celiac disease (Presutti 2007). If positive, the patient
vitamin B-12 values as high as 593pmol/L (800pg/ml) in should be promptly referred for small intestinal biopsy to
their serum (van Tiggelen 1983, van Tiggelen 1984). confirm a presumptive diagnosis of celiac disease. If small
intestinal bacterial overgrowth is suspected a urinary
In the absence of vitamin B-12 deficiency, a less common indican can be requisitioned, but it can also be indicative of
cause of megaloblastic anemia is folic acid deficiency. other problems, such as hypochlorhydria, gastric cancer and
Common causes of folic acid deficiency include malabsorption (Brummer 1956, Powell 1999).Patients with
alcoholism, severe hemolysis, chronic hemodialysis, vitamin B-12 deficiency should be given daily intramuscular
tropical sprue, celiac disease, Crohn’s disease, diabetic (IM) injections consisting of 1,000 mcg of cyanocobalamin
enteropathy and drug interference (Barkin 1998). While (or other forms of vitamin B-12) for five days, followed by
several authorities recommend testing folate status weekly IM injections for 4 weeks, and then IM injections
every 1 to 3 months thereafter (Little 1999). Even though count. If it is elevated, hemolysis and blood loss need to
hematological improvements begin within five to seven be investigated as potential causes. Fecal occult blood
days, the patient might require treatment for six months or testing will identify whether blood loss is coming from
longer to resolve neurological symptoms, which completely the gastrointestinal tract. A serum bilirubin and/or lactate
or partially resolve in some 80% of patients (Little 1999). dehydrogenase can identify hemolysis, but any positive
In situations of chronic vitamin B-12 deficiency, such as tests will need to be followed up with a direct Coomb’s
pernicious anemia or post-surgical malabsorption states, test to confirm immune hemolysis (Barkin 1998). If the
lifetime vitamin B-12 supplementation is necessary. These reticulocyte count is low, systemic disease needs to be ruled
patients can maintain adequate vitamin B-12 levels by out (Brill 2000) and a serum iron should be requisitioned
receiving IM injections every one to three months, or by (Barkin 1998). If the serum iron comes back within normal
taking 1,000-2,000mcg of oral vitamin B-12 daily as an limits or is elevated, the patient should be referred for a
alternative to parenteral therapy (Little 1999). Treatment bone marrow biopsy (Brill 2000). If the serum iron level
of suspected folic acid deficiency usually requires 1mg comes back below normal, anemia of chronic disease is
daily for three weeks to replenish stores (Davenport the diagnosis, which happens to be the most common
1996). In cases of malabsorption or when patients are cause of normocytic anemia (Brill 2000, Weiss 2005).
on medications that antagonize folic acid metabolism,
the dose and duration of treatment depend on repletion Common underlying causes of anemia of chronic disease
of deficient serum folate and/or red blood cell levels. In include chronic infections, cancers, autoimmune diseases,
these situations, it is probably best to ensure repletion by chronic rejection after solid-organ transplantation, and
measuring a patient’s folate status serially over time. chronic kidney disease (Weiss 2005). A serum ferritin
test cannot be used to diagnose anemia of chronic
Normocytic Anemia disease since it is either normal or elevated among
When the MCV is normal, the patient might simply be in patients with this type of anemia (Weiss 2005). In the
the early stages of iron deficiency, vitamin B-12 deficiency treatment of anemia of chronic disease, hematological
or folic acid deficiency (Barkin 1998). When these nutrient improvement can result when the underlying disease
deficiencies have been properly ruled out, the next step is treated, but patients might require transfusions
in the evaluation process is to requisition a reticulocyte and erythropoietic agents (Weiss 2005).
Donaldson MS. Metabolic vitamin B12 status on a mostly raw van Tiggelen CJ, Peperkamp JP, Tertoolen JF. Assessment of
vegan diet with follow-up using tablets, nutritional yeast, or vitamin B12 status in CSF. Am J Psychiatry 1984;141:136-7.