pernicious anemia (med.)



OVERVIEW

Definition

Anemia caused by vitamin B12 absorption disorder due to internal factor deficiency, which is a special type of megaloblastic anemia.

Intrinsic factor is produced in the mural cells of the body and fundus of the stomach and is a gastric mucin that accelerates the absorption of vitamin B12 in the mucosa of the small intestine.

Classification

Idiopathic pernicious anemia.

Symptomatic pernicious anemia: mainly pernicious anemia after gastrectomy.

Morbidity

Mostly found in Northern Europe, UK, Canada and USA, rare in China.

Most adult-type pernicious anemia occurs above 40 years of age, and the incidence increases with age.

Causes

Causes

Pernicious anemia occurs as a result of impaired absorption of vitamin B12 caused by a deficiency of endogenous factors.

Autoimmune disorders

Mainly seen in autoimmune gastritis (type A atrophic gastritis). The presence of anti-endogenin antibodies or anti-mural cell antibodies in the patient’s body leads to insufficient secretion of endogenin, which prevents the gastrointestinal tract from absorbing vitamin B12 properly and causes the disease.

It is also seen in certain diseases such as hyperthyroidism, chronic lymphocytic thyroiditis, rheumatoid arthritis, and vitiligo. Patients develop anti-endogenous factor antibodies and subsequently develop pernicious anemia.

Heredity

Pernicious anemia is also related to heredity, and the prevalence rate in patients’ families is 20 times higher than that of the general population.

Reduced endogenous factor secretion due to gastric diseases

Vitamin B12 malabsorption is caused by insufficient secretion of endogenous factor after gastrectomy and gastric cancer.

Pathogenesis

The exact pathogenesis of pernicious anemia is unclear, and current research suggests that it is related to internal factor deficiency.

Intrinsic factor (IF) is mainly secreted by gastric lining cells and is essential for the absorption of vitamin B12 in the gastrointestinal tract.

There are two types of antibodies against IF: Type I antibodies can block the combination of vitamin B12 and IF, so they are also called blocking antibodies; Type II antibodies can prevent the combination of IF-vitamin B12 complex and Cubam receptor at the end of the ileum, thus preventing the absorption of vitamin B12, so they are also called binding antibodies.

The presence of anti-endofactor antibodies in the serum can lead to insufficient secretion of endofactor, so that the gastrointestinal tract is unable to absorb vitamin B12 normally and result in megaloblastic anemia.

Symptoms

Major Symptoms

Mild pernicious anemia may be asymptomatic, and as vitamin B12 levels decline, the following manifestations may occur [1-4]:

Hematologic manifestations

There is often pallor and pallor of the mucous membranes on the inside of the eyelids.

Dizziness, fatigue, chest tightness and dyspnea after activity.

Headache, myalgia.

Digestive system manifestations

There may be atrophy of oral mucosa and tongue papillae, reddish tongue (“beefy tongue”), loss of sense of taste, which may be accompanied by tongue pain.

Lack of appetite, nausea, abdominal distension and diarrhea may occur.

Neurological manifestations and psychiatric symptoms

Neurological symptoms

Neurologic symptoms may appear earlier than anemia and are usually not reversible with treatment when the disease progresses to an advanced stage, and are mainly characterized by:

Symmetrical distal limb numbness: numbness and coldness of the extremities, some of which are accompanied by pain.

Deep sensory deficits: impairment of vision, smell, hearing, and taste.

Ataxia: disturbances in amplitude and coordination of movement, unsteady gait, weakness of limbs, difficulty in walking.

Amnesia, disorientation: lack of cognition or misperception of one’s own condition, person, place, time or environment.

Vision loss, blackouts.

In severe cases, there may be incontinence of urine and faeces.

Mental symptoms

Depression, insomnia, delusions, hallucinations, mania, and even psychosis, personality disorder and other mental abnormalities may occur in severe cases.

Others

Vitamin B12 deficiency may cause extensive skin pigmentation.

Hemolysis may cause jaundice.

Complications

Tumor

Pernicious anemia can lead to an increased risk of gastric cancer.

Bleeding tendencies

Pernicious anemia can cause thrombocytopenia and deficiency of certain clotting factors, which can lead to bleeding tendencies.

Skin petechiae, ecchymosis, purpura, bleeding gums, nosebleeds, and black stools may occur.

Infection

Pernicious anemia can cause a decrease in white blood cells and make you more susceptible to infections than usual.

Consultation

Department of Medicine

Hematology

Consultation with the Department of Hematology is recommended when symptoms such as pallor, dizziness, fatigue and chest tightness or palpitations after activity occur, or when a physical examination reveals that hemoglobin is lower than normal.

Gastroenterology

Consult the Department of Gastroenterology if you have symptoms such as loss of appetite, bloating and diarrhea.

Neurology

If you have symptoms such as numbness in the hands and feet, loss of sensation, difficulty walking, or drowsiness or confusion, consult the Department of Neurology.

Preparation for medical treatment

Consultation: Registration, Preparation of documents, Frequently Asked Questions

Tips for Consultation

It is recommended to rest in bed before the consultation to avoid falling due to dizziness.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Are there any symptoms such as pallor, dizziness, fatigue, chest tightness and palpitations after activity?

Is there a reddish tongue (“beefy tongue”), loss of taste, or tongue pain?

Do you have symptoms such as lack of appetite, nausea, abdominal distension, diarrhea, etc.?

Are there any symptoms such as numbness of hands and feet, loss of sensation, difficulty in walking or unsteady gait?

Is there any memory loss, lack of cognition or misperception of self, others, place, time or environment?

Is there any decrease or loss of taste or smell?

Any loss of vision or blackouts?

Any incontinence of urine or faeces?

Are there any symptoms of depression, insomnia, delusion, hallucination, mania, or even mental abnormality such as insanity or personality disorder?

Are there any skin abnormalities?

How long have these symptoms been present?

List of medical history

Is there autoimmune gastritis (type A atrophic gastritis)?

Any gastric cancer?

Are there any diseases such as hyperthyroidism, chronic lymphocytic thyroiditis, rheumatoid arthritis, or vitiligo?

Is there a history of pernicious anemia in the immediate family?

Is there any history of gastric surgery?

Checklist

Test results of the last six months, which can be brought to the doctor’s office

Laboratory tests: routine blood test, bone marrow cytology test, anemia quadruple test, etc.

Medication list

Medication in the last 3 months, if available in boxes or packages, bring with you to the doctor’s office

Anti-anemia drugs: vitamin B12, etc.

Diagnosis

Diagnosis based on

Medical history

History of autoimmune gastritis (type A atrophic gastritis), gastric cancer.

History of gastrectomy.

History of hyperthyroidism, chronic lymphocytic thyroiditis, rheumatoid arthritis, and vitiligo.

Family history of pernicious anemia.

Clinical manifestations

Symptoms

Pallor, dizziness, fatigue and chest tightness and palpitations after activity may occur.

There may be atrophy of oral mucosa and tongue papillae, reddish tongue (“beef-like tongue”), loss of taste, tongue pain, lack of appetite, nausea, abdominal distension, diarrhea and other gastrointestinal symptoms.

Neurological symptoms: fatigue, numbness of hands and feet, sensory disturbances, difficulty in walking, forgetfulness, disorientation, decreased or absent sense of taste and smell, decreased vision, blackouts, incontinence, etc.

Mental symptoms: depression, insomnia, delusion, hallucination and mania, even insanity, personality perversion.

Others: skin pigmentation changes, jaundice, etc.

Physical signs

Appears when the nervous system is involved.

Increased muscle tone, hyperreflexia of tendons.

Positive pyramidal fasciculus sign, including:

Positive Babinski’s sign: dorsiflexion of the thumb and fan spreading of the remaining four fingers when using a cotton swab to stroke from the heel along the lateral edge of the sole of the foot toward the base of the toes.

Positive Chaddock’s sign: dorsiflexion of the thumb and fanning of the remaining four fingers when the subject is gently tapped from the lower ankle to the metatarsophalangeal joints from the back to the front using the blunt end of a percussion hammer.

Positive Oppenheim’s sign: dorsiflexion of the thumb and fanning of the remaining four fingers when the subject is grasped with the thumb and forefinger at the superior aspect of the anterior border of the tibia and then pushed firmly downward along the anterior border of the tibia to the ankle.

Gordon’s sign: the thumb and four other fingers are placed on the gastrocnemius muscle and pinched with moderate force, resulting in dorsiflexion of the thumb and spreading of the other four fingers in a fan pattern.

Laboratory Tests

Blood tests

To find out about blood cells in the peripheral blood, often combined with a blood smear.

Pernicious anemia is usually a macrocytic normochromic anemia with a mean corpuscular volume (MCV) of >100fl, a lower than normal hemoglobin, and a decrease in both neutrophils and platelets, but less severe than hemoglobin.

Neutrophil multilobularity and large ovoid red blood cells are seen in blood smears.

Bone marrow cytology

To understand the hematopoietic condition of bone marrow.

Proliferation is active or markedly active, with significant proliferation of the red lineage, with megaloblastic cells of all lineages (large cytosol, more mature cytoplasm than nucleus, “old nucleus and young plasma”), and larger-than-normal cells at all stages of the red lineage.

Know the serum vitamin B12 level.

Serum vitamin B12 below 74 pmol/L (100 ng/ml) suggests vitamin B12 deficiency.

Note: Decreased levels of folate or vitamin B12 alone are not conclusive of the diagnosis.

It helps to determine the cause of vitamin B12 deficiency.

A Phase I test showing vitamin B12 deficiency is corrected by a Phase II test after oral administration of internal factors.

Mitochondrial Antibody Test

Can find out if mural cell antibodies are present and is used to determine the cause of the disease.

Mural cell antibodies can be detected in the serum or gastric fluid of most patients with pernicious anemia.

Caution: Seropositivity decreases with age.

Anti-Endokine Antibody Test

Provides information about the presence of anti-endofactor antibodies, which are used to diagnose the disease.

In the serum of patients with pernicious anemia, the detection rate of endofactor-blocking antibodies (type I antibodies) is more than 50%, so endofactor-blocking antibody assay is one of the screening methods for pernicious anemia.

Gastric fluid analysis

To find out the condition of gastric fluid.

The pH of gastric fluid in patients with pernicious anemia is above 3.5, free hydrochloric acid disappears, and injection of histamine or gastrin does not reduce the acidity of gastric fluid by 1 pH.

Grading

It can be graded by the degree of hemoglobin (Hb) decrease:

Mild anemia: Hb > 90 g/L but below the lower limit of normal reference values.

Moderate anemia: Hb 61 to 90g/L.

Severe anemia: Hb 31～60g/L.

Very severe anemia: Hb ≤30g/L.

Differential Diagnosis

Gastric cancer

Similarity: both can cause gastrointestinal symptoms such as loss of appetite, abdominal distension, diarrhea, etc. and lack of gastric free hydrochloric acid.

Differences: Gastroscopy and biopsy can be used for differentiation.

Hemolytic anemia

Similarity: symptoms of anemia, both can cause elevated bilirubin.

Difference: hemolytic anemia is often more obvious than pernicious anemia, and the hemolytic test is positive, which is not consistent with pernicious anemia.

Red Leukemia

Similarity: Both can cause anemia symptoms such as pallor, dizziness, fatigue, chest tightness and palpitation after activity, and both can lead to megaloblastic changes in red blood cells.

Differences: Bone marrow examination of erythroleukemia reveals an increase in the number of primitive cells, and treatment with vitamin B12 is ineffective.

Myelodysplastic syndrome

Similarities: both can cause anemia symptoms such as pallor, dizziness, fatigue, chest tightness and palpitation after activity; both can lead to megaloblastic changes in red blood cells.

Differences: Bone marrow examination in myelodysplastic syndromes reveals pathological hematopoiesis and no reduction in vitamin B12.

Treatment

Aim of treatment: to correct anemia, relieve symptoms and prevent complications.

Treatment principle: general treatment and drug treatment, mainly vitamin B12 lifelong treatment.

General treatment

Rest

When the symptoms of dizziness, fatigue and chest tightness are obvious, bed rest should be taken and activities should be reduced.

Blood transfusion

For Hb <50g/L, when the patient is extremely exhausted, infected or combined with heart failure, blood transfusion treatment can be carried out as appropriate.

Medication

Lifelong use of vitamin B12 is required.

Intramuscular injection is used.

Precautions: may induce uric acid elevation, so should pay attention to monitoring uric acid changes during the use of drugs; aminosalicylic acid and other drugs will affect the absorption, need to avoid concomitant use.

Prognosis

Cure

Lifelong medication is required and there is no cure.

Complicated neurological symptoms are usually difficult to fully recover.

Hazards

It can lead to decreased activity tolerance and memory loss, affecting normal life and work.

It can damage the nervous system, and recovery from neurological damage is slow or even impossible, affecting the quality of life.

It requires lifelong medication, and if it is stopped, serious symptoms may occur, affecting the quality of life.

Pernicious anemia may be the initial symptom of stomach cancer, or may complicate stomach cancer in the later stage, affecting the quality of life, and in serious cases, endangering life.

Daily

Daily Management

Dietary management

It is advisable to eat more fresh fruits and vegetables, meat, eggs and other high-protein, high-vitamin and easy-to-digest foods.

Maintain balanced nutrition.

Alcohol should be abstained.

Life Management

For mild anemia, there is no need for too much restriction, but attention should be paid to rest and avoid excessive fatigue.

For moderate anemia, increase the bed rest time. If the condition permits, self-care should be encouraged, and the amount of activity should be such that it does not aggravate the symptoms. If the self-measured pulse rate is ≥100 beats/minute or obvious palpitation or shortness of breath occurs during the activity, the activity should be stopped.

When the condition improves, the amount of activity can be gradually increased.

Keep the room clean and hygienic, and try to avoid going to crowded environments.

Psychological support

As pernicious anemia requires lifelong treatment, it is easy to cause psychological problems such as depression and agitation. The psychological condition can be improved through psychological counseling, basic knowledge of the disease, and companionship.

Disease monitoring

Intramuscular injection of vitamin B12 may occasionally cause allergic reactions or even shock, which should be closely observed and promptly treated by medical treatment.

After using the drug, due to the large number of hematopoietic cells, extracellular potassium ions can be moved inward, which can lead to a sudden decrease in blood potassium level, and the blood potassium concentration should be closely monitored and promptly seek medical treatment.

Follow-up review

Follow the doctor’s instructions for regular review so that the doctor can assess the condition and adjust the treatment plan.

The timing of follow-up examinations should be determined by the doctor according to the patient’s condition.

Follow-up examinations generally include routine blood tests, bone marrow cytology, vitamin B12 measurement, etc.

Prevention

The cause and pathogenesis of the disease are unknown, so there is no exact and effective preventive measure.

If the disease is caused by gastric cancer, it is necessary to actively treat the original disease.