Monday, May 1, 2017

Introduction to Pernicious Anemia



Pernicious anemia
is a decrease in red blood cells that occurs due to impaired absorption of vitamin B-12 because of a lack of intrinsic factor (IF) in gastric secretions.

It occurs as a relatively common adult form of anemia that is associated with gastric atrophy and a loss of IF production and as a rare congenital autosomal recessive form in which IF production is lacking without gastric atrophy.

By definition, pernicious anemia refers specifically to vitamin B-12 deficiency resulting from a lack of production of IF in the stomach.

Causes: Common causes of pernicious anemia include:
  • Weakened stomach lining (atrophic gastritis)
  • An autoimmune condition in which the body’s immune system attacks intrinsic factor protein or the cells that make it.
Very rarely, pernicious anemia is passed down through families. This is called congenital pernicious anemia. Babies with this type of anemia do not make enough intrinsic factor or cannot properly absorb vitamin 12 in the small intestine.

Pathology
Vitamin B12 cannot be produced by the human body, and must be obtained from the diet. Normally, dietary B12 is absorbed by the body in the small bowel only when it is bound by the intrinsic factor (IF) produced by parietal cells of the gastric mucosa. Pernicious anemia is thought to occur when the body’s immune system mistakenly targets the IF, with a loss of parietal cells. Insufficient IF results in insufficient absorption of the vitamin. Although the normal body stores three to five years’ worth of B12 in the liver, the usually undetected autoimmune activity in one’s gut over a prolonged period of time leads to B12 depletion and the resulting anemia. Inhibition of DNA synthesis in red blood cells results in the formation of large, fragile megaloblastic erythrocytes.

Clinical PresentationThe onset of pernicious anemia usually is insidious and vague. The classic triad of weakness, sore tongue, and paresthesias may be elicited but usually is not the chief symptom complex.

Common symptoms include fatigue, depression, forgetfulness, difficulty concentrating, low-grade fevers, nausea and gastrointestinal symptoms (heartburn), weight loss. Because PA may affect the spinal cord, symptoms may also include impaired urination, loss of sensation in the feet, unsteady gait, weakness, and clumsiness. Anemia may cause tachycardia (rapid heartbeat) and cardiac murmurs, along with a waxy pallor. In severe cases, the anemia may cause evidence of congestive heart failure.

Diagnosis
Workup for pernicious anemia may include the following:

Peripheral blood smear
The peripheral blood usually shows a macrocytic anemia with a mild leukopenia and thrombocytopenia. The mean cell volume (MCV) and mean cell hemoglobin (MCH) are increased. The leukopenia and thrombocytopenia usually parallel the severity of the anemia.

Indirect bilirubin and Lactate dehydrogenase Assays
The indirect bilirubin level may be elevated because pernicious anemia is a hemolytic disorder associated with increased turnover of bilirubin. The serum lactic dehydrogenase (LDH) concentration usually is markedly increased.

Evaluation of Gastric secretions
Total gastric secretions are decreased to about 10% of the reference range.

Serum Cobalamin
The serum cobalamin level is low in patients with pernicious anemia.

Serum Methylmalonic acid and homocysteine Assays
Elevated serum methylmalonic acid and homocysteine levels are found in patients with pernicious anemia. They probably are the most reliable test for cobalamin deficiency in patients who do not have a congenital metabolism disorder.

Schilling test
The Schilling test measures cobalamin absorption by assessing increased urine radioactivity after an oral dose of radioactive cobalamin. The test is useful in demonstrating that the anemia is caused by an absence of IF and is not secondary to other causes of cobalamin deficiency. It is also useful for identifying patients with classic pernicious anemia, even after they have been treated with vitamin B-12.

Management: The following goals are the most important in establishing care for patients with pernicious anemia:
  • To establish that the patient has cobalamin deficiency
  • If there is evidence for folic acid deficiency but pernicious anemia has not been ruled out, treat with both folic acid and cobalamin until pernicious anemia has been ruled out.
  • To determine the cause of the failure to absorb cobalamin.
  • To treat the patient with adequate doses of cobalamin
  • To confirm the diagnosis by documenting that specific therapy is effective
  • To ensure administration of adequate quantities of cobalamin for the lifespan of the patient.
  • Treatment involves a shot of vitamin B12 once a month. Persons with severely low levels of B12 may need more shots in the beginning.
  • Some patients may also need to take vitamin B12 supplements by mouth. For some people, high-dose vitamin B12 tablets taken by mouth work well, and shots are not needed.
  • A certain type of vitamin B12 may be given through the nose.
Dietary Advice
People who are strict vegetarians and, most particularly, people who do not consume eggs, milk, or meat can develop cobalamin deficiency. Counsel these people to either change their dietary habits or remain on supplementary vitamin B-12 therapy for their lifetime. An oral tablet of 100-200 ยตg taken weekly should provide adequate therapy.

Complications
People with pernicious anemia may have gastric polyps, and are more likely to develop gastric cancer and gastric carcinoid tumors.

Brain and nervous system problems may continue or be permanent if treatment is delayed.

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