Pernicious Anemia: Causes, Diagnosis, and Treatment

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Overview and Pathophysiology

Pernicious anemia is a chronic autoimmune disorder that results in vitamin B12 (cobalamin) deficiency due to impaired absorption in the gastrointestinal tract. The condition develops when the immune system mistakenly produces antibodies against intrinsic factor or against the gastric parietal cells responsible for intrinsic factor production. Without sufficient intrinsic factor, vitamin B12 cannot be properly absorbed in the terminal ileum of the small intestine.

Vitamin B12 plays a crucial role in red blood cell formation, DNA synthesis, and maintenance of the nervous system. When absorption is impaired, progressive hematologic and neurological complications may occur.

What Causes Pernicious Anemia?

Under normal physiological conditions, dietary vitamin B12 is released from food in the stomach and binds to intrinsic factor, a glycoprotein secreted by parietal cells in the gastric mucosa. The intrinsic factor–B12 complex then travels to the terminal ileum, where it binds to specific receptors and is absorbed into the bloodstream.

In pernicious anemia:

  • The immune system may produce antibodies against intrinsic factor, blocking vitamin B12 binding or preventing intestinal absorption.

  • Alternatively, antibodies may target gastric parietal cells, reducing intrinsic factor production and often leading to chronic atrophic gastritis.

Because intrinsic factor is essential for efficient vitamin B12 absorption, its deficiency gradually leads to vitamin B12 depletion. Since the body stores B12 in the liver, symptoms may take years to appear.

Symptoms

Because vitamin B12 is essential for red blood cell formation and nervous system function, deficiency can cause:

  • Fatigue and weakness

  • Pale skin

  • Shortness of breath

  • Glossitis (inflamed, smooth tongue)

  • Numbness or tingling in the hands and feet

  • Memory problems or difficulty concentrating

  • Balance problems

  • Muscle weakness (SMA)

Muscle weakness may result from neurological impairment due to demyelination of peripheral nerves and spinal cord involvement. In patients with underlying neuromuscular disorders—such as spinal muscular atrophy type 4 (SMA4)—vitamin B12 deficiency may further worsen muscle weakness and functional impairment.

If untreated, neurological damage may become permanent.

Blood Tests for Diagnosis

Diagnosis is based on clinical findings and laboratory testing.

1. Complete Blood Count (CBC)

  • Low hemoglobin

  • Low red blood cell count

  • Increased mean corpuscular volume (MCV) → macrocytic (megaloblastic) anemia

2. Serum Vitamin B12 Level

  • Low vitamin B12 concentration

3. Intrinsic Factor Antibodies

  • Positive intrinsic factor antibodies strongly suggest pernicious anemia

4. Parietal Cell Antibodies

  • May also be detected and support the diagnosis

5. Additional Tests (if needed)

  • Elevated methylmalonic acid (MMA)

  • Elevated homocysteine

  • Reticulocyte count

  • Gastrin levels (sometimes elevated due to chronic gastric atrophy)

These laboratory findings help confirm both vitamin B12 deficiency and its autoimmune cause.

Treatment Options

The goal of treatment is to restore and maintain adequate vitamin B12 levels and prevent complications.

1. Vitamin B12 Injections

This is the standard treatment.

  • Intramuscular vitamin B12 (usually hydroxocobalamin or cyanocobalamin)

  • Often administered frequently at the beginning (e.g., weekly), then every 1–3 months for life

  • Because intestinal absorption is impaired, injections bypass the need for intrinsic factor

2. High-Dose Oral Vitamin B12

In some cases, very high oral doses can be effective because a small percentage of vitamin B12 is absorbed passively without intrinsic factor. This approach may be suitable for selected patients under medical supervision.

3. Monitoring

Regular follow-up includes:

  • Repeat blood counts

  • Monitoring vitamin B12 levels

  • Neurological assessment

  • Evaluation of symptom improvement

Prognosis

With proper treatment, most patients recover well. Blood counts typically improve within weeks, and energy levels often increase rapidly. Neurological symptoms—including muscle weakness—may improve if therapy is started early. However, delayed diagnosis and prolonged deficiency can lead to irreversible nerve damage.

Because pernicious anemia is an autoimmune condition, treatment is usually lifelong.

Summary

Pernicious anemia is an autoimmune disorder that prevents vitamin B12 absorption due to intrinsic factor deficiency. It is diagnosed through blood tests showing macrocytic anemia, low vitamin B12 levels, and the presence of specific antibodies. Lifelong vitamin B12 replacement therapy—most commonly administered via intramuscular injections—is the mainstay of treatment and is highly effective in preventing serious hematologic and neurological complications.

 

References:

Pernicious Anemia
https://my.clevelandclinic.org/health/diseases/22377-pernicious-anemia?utm_source=chatgpt.com

Vitamin B12 Deficiency https://www.ncbi.nlm.nih.gov/books/NBK441923/?utm_source=chatgpt.com

Intrinsic Factor Antibody
https://www.testing.com/tests/intrinsic-factor-antibody/?utm_source=chatgpt.com

Vitamin B12 deficiency and pernicious anaemia
https://info.health.nz/health-topics/conditions-treatments/blood/vitamin-b12-deficiency-and-pernicious-anaemia?utm_source=chatgpt.com

Vitamin B12 deficiency in over 16s: diagnosis and management
https://www.nice.org.uk/guidance/ng239/chapter/recommendations?utm_source=chatgpt.com

Treatment & Management

Pernicious anemia
https://medlineplus.gov/ency/article/000569.htm?utm_source=chatgpt.com

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9  

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