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Dr. Andrew Rynne
Dr. Andrew Rynne

Family Physician

Exp 50 years

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Article Home Adult and Senior Health Pernicious Anemia

Pernicious Anemia

Pernicious anemia is a form of megaloblastic anemia due to vitamin B-12 deficiency, caused by impaired absorption of vitamin B-12 due to the absence of intrinsic factor in the setting of atrophic gastritis, and more specifically of loss of gastric parietal cells. The loss of ability to absorb vitamin B-12 is the most common cause of adult vitamin B-12 deficiency.


  • An increased incidence of pernicious anemia in families suggests a hereditary component to the disease.
  • Patients with pernicious anemia have an increased incidence of autoimmune disorders and thyroid disease, suggesting that an immunological component to the disease exists.
  • Most commonly (in temperate climates), the cause for impaired binding of vitamin B-12 by intrinsic factor is autoimmune atrophic gastritis, in which auto antibodies are directed against parietal cells (resulting in their loss) as well as against the intrinsic factor itself (rendering it unable to bind vitamin B-12).
  • Less frequently, loss of parietal cells may simply be part of a widespread atrophic gastritis of non-autoimmune origin, such as that frequently occurring in elderly people affected with long-standing chronic gastritis of any cause (including Helicobacter pylori infection).
  • Genetic defects of the ileal receptors for IF (ie, Imerslünd-Grasbeck syndrome) and hereditary transcobalamin I (TC I) deficiency produce cyanocobalamin deficiency from birth and are usually discovered early in life.

Signs and Symptoms

The classic triad of weakness, sore tongue, and paresthesias may be elicited but usually is not the chief symptom complex.

Nervous system

  • Neurological symptoms can be elicited in most patients with pernicious anemia, and the most common symptoms are paresthesias, weakness, clumsiness, and an unsteady gait.
  • These neurological symptoms are due to myelin degeneration and loss of nerve fibers in the dorsal and lateral columns of the spinal cord and cerebral cortex.
  • Neurological symptoms and findings may be present in the absence of anemia; this is more common in patients taking folic acid or on a high-folate diet.
  • Megaloblastic madness is less common and can be manifested by delusions, hallucinations, outbursts, and paranoid schizophrenic ideation.
  •  Loss of position sense in the second toe and loss of vibratory sense for a 256-Hz but not a 128-Hz tuning fork are the earliest signs of posterolateral column disease.
  • If untreated, this can progress to spastic ataxia from demyelinization of the dorsal and lateral columns of the spinal cord.
  • Suspect pernicious anemia in all patients with recent loss of mental capacities. Somnolence, dementia, psychotic depression, and frank psychosis may be observed, which can be reversed or improved by treatment with cyanocobalamin.
  •  Perversion of taste and smell and visual disturbances, which can progress to optic atrophy, can likewise result from central nervous system deficiency.

Gastrointestinal findings

  • Approximately 50% of patients have a smooth tongue with loss of papillae.
  • This is usually most marked along the edges of the tongue.
  • The tongue may be painful and beefy red. Occasionally, red patches are observed on the edges of the dorsum of the tongue.
  • Patients may report burning or soreness, most particularly on the anterior one third of the tongue.
  • These symptoms may be associated with changes in taste and loss of appetite.
  • Patients may report either constipation or having several semisolid bowel movements daily. This has been attributed to megaloblastic changes of the cells of the intestinal mucosa.
  • Nonspecific gastrointestinal symptoms are not unusual and include anorexia, nausea, vomiting, heartburn, pyrosis, flatulence, and a sense of fullness.

Genito urinary findings

Urinary retention and impaired micturition may occur because of spinal cord damage. This can predispose patients to urinary tract infections.

Stereotypic appearance

  • Patients have a lemon-yellow waxy pallor with premature whitening of the hair.
  • They appear flabby, with a bulky frame that is generally incongruent with the severe anemia and weakness.
  • Tachycardia often is present and may be accompanied by flow murmurs.

Other symptoms

  • With severe anemia, dyspnea, tachypnea, and evidence of congestive heart failure may be present.
  • Retinal hemorrhages and exudates may accompany severe anemia.
  • The liver may be enlarged in association with congestive heart failure.
  • A splenic tip is palpable in about 20% of patients.

Tests and diagnosis

Peripheral 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, with a mean corpuscular hemoglobin concentration (MCHC) within the reference range.
  • The peripheral smear shows oval macrocytes, hypersegmented granulocytes, and anisopoikilocytosis.
  • In severe anemia, red blood cell inclusions may include Howell-Jolly bodies, Cabot rings, and punctate basophilia.

Other tests

  • The indirect bilirubin may be elevated because pernicious anemia is a hemolytic disorder.
  • The serum lactic dehydrogenase usually is markedly increased. Increased values for other red blood cells, enzymes, and serum iron saturation also are observed.
  • The serum potassium, cholesterol, and skeletal alkaline phosphatase often are decreased.
  • Total gastric secretions are decreased to about 10% of the reference range.
  • Most patients with pernicious anemia are achlorhydric, even with histamine stimulation.
  • IF is either absent or markedly decreased.
  • Elevated serum methylmalonic acid and homocysteine levels are found in patients with pernicious anemia.
  • The serum cyanocobalamin is low in patients with pernicious anemia
  • Bone marrow aspiration and biopsy

Schilling test

The Schilling test measures cyanocobalamin absorption by increasing urine radioactivity after an oral dose of radioactive cyanocobalamin.


  • People who are strict vegetarians and, most particularly, people who do not consume eggs, milk, or meat can develop cyanocobalamin deficiency.
  • Vitamin B-12 is available for therapeutic use parenterally as either cyanocobalamin or hydroxocobalamin. Available orally and as IM injections


  • Neurological complications can become permanent.
  • Severe anemia can cause congestive heart failure or precipitate coronary insufficiency.
  • The incidence of gastric adenocarcinoma is 2- to 3-fold greater in patients with pernicious anemia than in the general population of the same age.



  • Early recognition and treatment of pernicious anemia provides a normal, and usually uncomplicated, lifespan.
  • Delayed treatment permits progression of the anemia and neurological complications.
  • The mental and neurological damage can become irreversible without therapy.