What Are Pernicious Anemia Symptoms?

Malignant anemia is a megaloblastic anemia that occurs due to atrophy of the gastric mucosa and lack of internal factors in the gastric juice, which impairs the absorption of vitamin B12. The pathogenesis is unclear and is related to race and genetics. About 90% of patients have parietal cell antibodies in serum, 60% of patients found endogenous antibody antibodies in serum and gastric juice, and some patients may develop thyroid antibodies. Malignant anemia can be seen in diseases such as hyperthyroidism, chronic lymphocytic thyroiditis, and rheumatoid arthritis. The treatment of pernicious anemia is vitamin B ₁₂ supplementation, which requires life-long maintenance treatment.

Basic Information

English name: perniciousanemia
Visiting department: Hematology

Common causes: Gastric mucosa atrophy, lack of internal factors, leading to vitamin B12 malabsorption
Contagious: no

Causes of pernicious anemia

The disease of pernicious anemia is due to atrophy of gastric mucosa and lack of internal factors, resulting in vitamin B ₁₂ malabsorption. The pathogenesis is unknown, and it is related to race and genetics. More common in Scandinavian, English and Irish people. Rarely in Southern Europe, Asia and Africa. There have been few reports in the country. Anti-gastric cell antibodies can be detected in the serum and gastric juice of most patients, so malignant anemia is considered an autoimmune disease. The occurrence of pernicious anemia is the result of a complex interaction between genetic and autoimmune factors. It is also believed that these antibodies against gastric parietal cells are only incidental to the released antigen after the gastric mucosa is destroyed for unknown reasons.

Clinical manifestations of malignant anemia

Anemia manifestation

Those with vitamin B ₁₂ deficiency usually have insidious onset, manifested as fatigue, dizziness, shortness of breath, palpitations, and pale complexion. Patients with severe anemia may have mild jaundice, and may have both white blood cell count and low platelets. Patients may have infection and bleeding tendency .

2. Gastrointestinal symptoms

Such as loss of appetite, bloating, diarrhea, and glossitis, etc., glossitis is the most prominent, red tongue, tongue atrophy, smooth surface, commonly known as "beef tongue", with pain.

3. Nervous system symptoms

Vitamin B ₁₂ deficiency is often accompanied by neurological manifestations, especially in patients with malignant anemia. Mainly due to damage to the spinal cord, lateral cord and peripheral nerves. It is manifested as weakness, numbness of symmetry of hands and feet, sensory disturbance, unstable gait of lower limbs, and difficulty walking. Pediatrics and the elderly often show neurological disorders, anorexia, depression, lethargy, or insanity. In some patients, neurological symptoms can occur before anemia.

The above three groups of symptoms can coexist in patients with pernicious anemia, or they can occur separately. The severity can also be inconsistent when present.

Examination for pernicious anemia

Blood image

It is large cell positive pigment anemia (MCV> 100fl), and both neutrophils and platelets can be reduced. Blood smears show that most of the large oval red blood cells and neutrophils have too many leaves, and there can be 5 or more leaves. Occasionally see huge platelets. Reticulocyte counts were normal or slightly elevated.

Bone marrow

Bone marrow hyperplasia is active, and erythroid cell proliferation is significantly increased. The cells of each line are megalomorphic, with erythroid cells being the most prominent. The erythroid cells are larger than normal at all stages, the cytoplasm is more mature than the nucleus (imbalanced nuclear development), and the nuclear chromatin is concentrated and dispersed. Similar morphological changes can also be seen in granulocytes and megakaryocytes, especially in young and rod-shaped nucleus cells.

3. Determination of serum vitamin B ₁₂ levels

Microbial and radioimmunoassay are commonly used for measurement. The latter is convenient for measurement and is commonly used in clinical practice. The normal range of serum vitamin B ₁₂ is 200-900 pg / ml. Serum vitamin B ₁₂ <200pg / ml can diagnose vitamin B12 deficiency. Many factors can affect the determination of serum vitamin B _12. Folic acid deficiency, pregnancy, oral contraceptives, multiple myeloma, and high-dose vitamin C treatment can cause false serum vitamin B ₁₂ deficiency; increased serum vitamin B ₁₂ measurement is also seen in Myeloproliferative disease, liver tumors, active liver disease, and intestinal bacterial overproduction. Therefore, to evaluate the clinical significance of serum vitamin B _12, serum folic acid value should be measured at the same time.

4. Determination of serum homocysteine and methylmalonic acid levels

To diagnose and distinguish folic acid deficiency or vitamin B ₁₂ deficiency. Serum cysteine (normal value: 5-16 mol / L) increased during folate deficiency and vitamin B ₁₂ deficiency, reaching 50-70 mol / L. Elevated serum methylmalonic acid levels (normal values of 70 to 270 nmol / L) can only be seen in the absence of vitamin B12, which can reach 3500 nmol / L.

5. Determination of internal factor antibodies

In the serum of patients with malignant anemia, the detection rate of internal factor blocking antibodies (type I antibodies) is more than 50%, so the measurement of internal factor blocking antibodies is one of the screening methods for malignant anemia. If positive, a vitamin B ₁₂ absorption test should be performed.

6. Vitamin B12 absorption test (Schillingtest)

Mainly used to determine the cause of vitamin B ₁₂ deficiency. The method is: intramuscularly inject 1000 g of vitamin B ₁₂ into a patient, and orally take 57Co labeled vitamin B ₁₂ 0.5 Ci at the same time or one hour later. Urine was collected for 24 hours, and the content of 57Co vitamin B ₁₂ in urine was measured. Normal people should be> 8%, patients with megaloblastic anemia and vitamin B ₁₂ malabsorption are <7%. Patients with pernicious anemia are <5%. If the test is repeated after 5 days, while oral internal factor 60mg, urine 57Co vitamin B ₁₂ excretion returns to normal, indicating that the patient's vitamin B ₁₂ deficiency is due to internal factor deficiency, otherwise it is caused by other reasons. If the test is corrected 7 to 10 days after the antibiotic is administered to the patient, it indicates that the absorption disorder of vitamin B ₁₂ is caused by the intestinal bacteria's excessive reproduction. The results of this test are related to urine output. It is important to accurately collect the urine output for 24 hours and to know the renal function of the tester in advance.

7. Other

In patients with pernicious anemia, free gastric acid disappeared from the gastric fluid and did not appear after histamine injection.

Diagnosis of pernicious anemia

1. Identify megaloblastic anemia

According to the medical history and clinical manifestations, the blood picture showed large cell anemia (MCV> 100fl), and the neutrophil had too many leaves (5 leaves accounted for more than 5% or 6 leaves). Bone marrow cells exhibit typical macro- and juvenile changes to confirm the diagnosis.

2. Determine Vitamin B ₁₂ Deficiency

Serum vitamin B ₁₂ levels should be measured, such as <200pg / ml indicates a deficiency. Further determination of serum homocysteine or methylmalonic acid to confirm.

3. Identify the cause of vitamin B ₁₂ deficiency

Further determination of internal factor blocking antibodies and vitamin B ₁₂ absorption test.

Differential diagnosis of pernicious anemia

It is distinguished from megaloblastic anemia caused by folate deficiency, and the serum and erythrocyte folic acid levels are measured; from vitamin B ₁₂ deficiency caused by other reasons, internal factor blocking antibodies and vitamin B ₁₂ absorption tests are measured.

Treatment of pernicious anemia

Intramuscular injection of vitamin B ₁₂ (or once every other day) until hemoglobin returns to normal. Patients with pernicious anemia need maintenance treatment for life. Vitamin B ₁₂ deficiency with neurological symptoms varies in response to treatment, and sometimes requires large doses and long-term (more than six months) treatment.