Describe his peripheral blood smear findings.
His peripheral blood smear shows red blood cells displaying macro-ovalocytosis and neutrophils with nuclear hypersegmentation. There is no obvious cause for the thrombocytosis and leukocytosis in this case.
What is the diagnosis from these findings?
This is a macrocytic (megaloblastic) anemia. The neurologic findings suggest vitamin B12 deficiency (pernicious anemia).
Which of the following tests would be most useful to determine the
etiology for these findings?
- A. Hemoglobin electrophoresis
- B. Reticulocyte count
- C. Stool for occult blood
- D. Vitamin B12 assay
- E. Bone marrow biopsy
Answer: D Macrocytic anemia could also be caused by a folate deficiency, but the neurologic findings would not be present.
How do you explain his neurologic findings?
The B12 deficiency leads to a subacute combined degeneration of the spinal cord (posterior and lateral columns).
How do treat his condition?
Most diets contain sufficient cobalamin, which is stored in the liver to provide a buffer against short-term dietary deficiencies. Lacto-ovo-vegetarian diets have minimal cobalamin. Cobalamin is released from food such as meat products by the action of acid and pepsin in the stomach, and this process is less efficient in the elderly. Gastric diseases such as atrophic gastritis, or gastrectomy, reduce or eliminate the parietal cells that produce intrinsic factor required for B12 binding and absorbtion. Intestinal abnormalities, particularly those involving the ileum where the B12 complexed with intrinsic factor is absorbed, may lead to deficiency.
Persons with chronic problems absorbing B12 can be given parenteral therapy in the form of intramuscular cyanocobalamin, typically 1000 micrograms of cobalamin per week for 2 months and then 1000 micrograms of cyanocobalamin intramuscularly every month thereafter. Persons who can still absorb cobalamin can be treated for deficiency with oral replacement therapy consisting of 2 mg of crystalline B12 per day.
Folic acid is mainly found in vegetable products, and it is not stored, so deficiencies come from poor diets. Many food products, such as cereals, contain folate supplementation. Folate deficiency may also be caused by malabsorbtion. There can be a relative lack of folate when there is increase erythropoiesis.
Folate deficiency is treated with an oral dose of 1 mg per day. Malabsorbtion may require higher doses of up to 5 mg per day.
Drugs that inhibit DNA synthesis (some chemotherapeutic agents such as hydroxyurea or 5-fluorouracil) and drugs that are folate antagonists such as methotrextate can produce megaloblastic anemia.
What are issues involved in designing a study to measure the effects of these treatments? Define selection, randomization, assignment, internal validity, external validity.
Would you select persons who already had the disease? If so, would it be ethical to delay treatments that might work? Would you select healthy persons from the general population to measure any effect of the treatments? If so, would the treatments have any adverse effects? Would an effect be noted? In the case of augmenting diets with folate and/or B12 there are unlikely to be adverse effects. Even a single injection of B12 is unlikely to have adverse outcomes.
Selection is the process by which a sample is recruited from a population. If the sample selected is truly random then observations from this population will be expected to yield a sample that is representative of the entire population.
However, recruitment is often not random. Instead, studies often rely on volunteers, and this is "self-selection" which is a non-random recruitment. This could constrain the population and hinder the ability to generalize any study findings.
Assignment is the process by which a sample is further divided into experimental and control groups. A random assignment of the sample will be expected to generate groups that are similar and, hence, any difference between them will be due to the experimental conditions. Any non-random assignment will limit a study's ability to control for non-experimental characteristics.
Thus, randomization of a self-selected (volunteer) sample will generally produce similar experimental and control groups and yield results close to those of a truly random sample selection process.
Internal validity refers to the validity of the sample observed in a study and the conditions under which the data were gathered for that particular study.
External validity refers to the validity of generalizing the sample data from the study to the population as a whole.