What Is Megaloblastic Anemia?

Megaloblastic anemia, the normative name is megaloblastic anemia, is an anemia caused by a disorder of DNA synthesis. It is mainly caused by a lack of vitamin B ₁₂ and / or folic acid in the body. It can also be caused by heredity. Or acquired DNA synthesis disorders. This disease is characterized by large red blood cell anemia, giant juvenile red blood cell series appearing in the bone marrow, and giant changes in cell morphology are also seen in granulocytes, megakaryocytes, and even some proliferative somatic cells. The giant juvenile red blood cells are easily destroyed in the bone marrow, and invalid red blood cells appear.

Basic Information

English name: megaloblastic anemia
Visiting department: Hematology

Common causes: Folic acid or (and) vitamin B12 deficiency
Common symptoms: Anemia, recurrent glossitis, loss of appetite, abdominal distension, etc.

Causes of megaloblastic anemia

The cause of megaloblastic anemia is mainly due to folic acid or / and vitamin B ₁₂ deficiency.

1. Causes of folic acid deficiency

(1) The daily requirement of inadequate folic acid is 200-400 µg. The amount of folic acid stored in the human body is only sufficient for 4 months. The lack of fresh vegetables in food, overcooking, or pickling can cause folic acid loss. Ethanol can interfere with folic acid metabolism, and alcoholics often have folic acid deficiency. Inflammation of the small intestine (especially the jejunum), tumors, surgical resection, and tropical oral inflammatory diarrhea can all lead to insufficient absorption of folic acid.

(2) The daily requirement of folic acid for pregnant women needs to be increased to 400 600µg. Growth and development of children and adolescents, as well as patients with chronic repeated hemolysis, leukemia, tumors, hyperthyroidism and long-term chronic renal failure treated with hemodialysis, the need for folic acid will increase, if there is insufficient supplementation, folic acid deficiency can occur.

(3) The effects of drugs such as methotrexate, amphitrazine, and pyrimethamine can inhibit the effect of dihydrofolate reductase and affect the production of tetrahydrofolate. The mechanism of the effects of phenytoin sodium and phenobarbital on folic acid is unknown, which may be to increase the decomposition of folic acid or inhibit DNA synthesis. About 67% of patients taking oral sulfasalazine inhibit folic acid absorption in the intestine.

(4) Other patients with congenital deficiency of 5,10-formyltetrahydrofolate reductase are often diagnosed around 10 years of age. Patients in some intensive care units (ICUs) often suffer from acute folic acid deficiency.

2. Causes of Vitamin B ₁₂ Deficiency

(1) Reduced intake The amount of vitamin B ₁₂ stored in the human body is about 2 to 5 mg, and the daily requirement is only 0.5 to 1 µg. Normally, 5 to 10 µg of vitamin B ₁₂ enters the intestinal cavity with bile every day, and internal factors secreted by the stomach wall can be sufficient to help reabsorb vitamin B _{12 in} bile. Therefore, it usually takes about 10-15 years for vegetarians to develop vitamin B ₁₂ deficiency. In the elderly and patients with gastrectomy, gastric acid secretion is reduced and vitamin B ₁₂ deficiency is common. Due to the reabsorption of vitamin B ₁₂ in the bile (intestinal-hepatic circulation), these patients, like vegetarians, take 10 to 15 years before clinical manifestations of vitamin B ₁₂ deficiency occur. Therefore, megaloblastic anemia is generally rare due to insufficient intake of vitamin B _{12 in the} diet.

(2) Endogenous factor deficiency is mainly seen in patients with atrophic gastritis, total gastrectomy and malignant anemia. The mechanism by which pernicious anemia occurs is unclear. Patients often have idiopathic complete atrophy of gastric mucosa and the presence of antibodies to internal factors, so some people think that malignant anemia is an immune disorder. Due to the lack of internal factors in these patients, the absorption of vitamin B ₁₂ in food and the reabsorption of vitamin B ₁₂ in bile have obstacles.

(3) Severe pancreatic exocrine secretion. Such patients are prone to malabsorption of vitamin B ₁₂ , because the vitamin B ₁₂ -R protein complex in the jejunum needs to be degraded by trypsin, and vitamin B ₁₂ can be released. Combine. The clinical manifestations of vitamin B ₁₂ deficiency in these patients generally occur after 3 to 5 years. Because patients with chronic pancreatitis usually supplement trypsin in time, it is not common to have vitamin B ₁₂ deficiency in clinical practice.

(4) Bacteria and parasites The abnormally high concentration of bacteria and parasites in the small intestine can also affect the absorption of vitamin B ₁₂ , because these organic substances can absorb and retain vitamin B _{12 in} large quantities. Small intestinal diverticulum or blind end salamanders after surgery often have bacteria breeding and fish ascarids produced in the intestines, which will compete with the human body for vitamin B ₁₂ and cause vitamin B ₁₂ deficiency.

(5) Lack of congenital trans-cobalt protein (TC) and exposure to nitrous oxide (anesthetic) can affect the plasma transport and intracellular utilization of vitamin B ₁₂ , and can also cause vitamin B ₁₂ deficiency.

Clinical manifestations of megaloblastic anemia

1. General clinical manifestations

(1) The onset of anemia and anaemia is insidious, especially those with vitamin B ₁₂ deficiency often take months. However, due to the small amount of folic acid stored in the body, deficiency can occur quickly. Some people exposed to nitrous oxide, ICU wards or hemodialysis patients, and pregnant women may develop deficiency in a short period of time. Clinically, they usually show moderate to severe anemia, and the symptoms of anemia, such as fatigue, dizziness, shortness of breath after activity, etc. In addition, patients with severe anemia may have mild jaundice, may have both white blood cell count and thrombocytopenia, and the patient may have infection and bleeding tendency

(2) Symptoms of the gastrointestinal tract Gastrointestinal symptoms are recurrent cheilitis, the surface of the tongue is smooth, the papillae and the taste disappear, and the appetite is not good. Bloating, diarrhea, and constipation occasionally.

(3) Nervous system symptoms Vitamin B ₁₂ deficiency, especially in patients with malignant anemia, often have neurological symptoms, 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. Neurological symptoms in some patients with megaloblastic anemia can occur before anemia.

The above three groups of symptoms may coexist or occur separately in patients with megaloblastic anemia, and their severity may also be inconsistent when they are present.

2. Special types of clinical manifestations

(1) Glia enteropathy and celiac disease (non-tropical oral inflammatory diarrhea or idiopathic fatty diarrhea) Glia enteropathy is referred to as celiac disease in children, and it is common in temperate regions. Its incidence and consumption of certain cereals It is related to gluten, and patients have difficulty in absorbing various nutrients, such as fat, protein, carbohydrates, vitamins, and minerals. Clinical manifestations are fatigue, intermittent diarrhea, weight loss, indigestion, bloating, glossitis and anemia. The stool was watery or pasty, with a lot of foam, a lot of odor, and a lot of fat. Blood and bone marrow signs are typical of megaloblastic anemia, and serum and red blood cell folate levels are reduced. Treatment is mainly symptomatic and folic acid supplementation, which can achieve better results. After anemia is corrected, low-dose folic acid should be used for maintenance treatment. It is also important not to eat foods containing gluten.

(2) Tropical oral inflammatory diarrhea (tropical trophoblastic anemia) The etiology of this disease is unclear. More common in residents and tourists in tropical regions such as India, Southeast Asia, Central America and the Middle East. Clinical symptoms are similar to gluten bowel disease. Decreased serum folate and erythrocyte folate levels, treatment with folic acid and broad-spectrum antibiotics can alleviate symptoms and correct anemia. After remission, low-dose folic acid maintenance treatment should be used to prevent recurrence.

(3) Orotic aciduria orotic aciduria is an inherited disorder of pyrimidine metabolism. In addition to megaloblastic anemia, mental retardation and orotic acid crystals appear in the urine. The patient's serum folic acid or vitamin B ₁₂ concentration is not low, treatment with folic acid or vitamin B _{12 is} not effective, and treatment with uracil can correct anemia.

(4) Malignant anemia Malignant anemia occurs due to atrophy of the gastric mucosa and lack of internal factors in the gastric juice, so that it cannot absorb vitamin B ₁₂ and is a megaloblastic anemia. The pathogenesis is unknown, but seems to be related to race and genetics. My country is rare.

Megaloblastic anemia

Blood image

In large cell positive pigment anemia (MCV> 100fl), the blood image often shows a decrease in whole blood cells. Both neutrophil and platelet counts are reduced, but to a lesser extent than anemia. Most of the large oval red blood cells can be seen in the blood smear. The neutrophils have too many leaves, and there can be 5 or more leaves. Occasionally see huge platelets. Reticulocyte counts were normal or slightly elevated.

2. Myeloid image <br /> Bone marrow showed hyperplasia, red cell proliferation was obvious, and cells of each line had giant juvenile changes, with red cells being the most prominent. Cells in the red line are larger than normal, the cytoplasm is more mature than the nucleus (imbalanced nucleus 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 granulocytes.

3. Biochemical examination

Serum folic acid and / or vitamin B ₁₂ levels are lower than normal, but because the effects of these two types of vitamins are in the cell, not in the plasma, the red blood cell folic acid level, serum homocysteine, and methylmalonic acid can be further determined Acid levels .

4. 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, vitamin B ₁₂ absorption test should be done

5. Vitamin B ₁₂ absorption test

Mainly used to determine the cause of vitamin B ₁₂ deficiency.

Diagnosis of megaloblastic anemia

1. The etiology and clinical manifestations of folic acid and vitamin B ₁₂ deficiency.

2. Peripheral blood showed large cell anemia (MCV> 100fl), neutrophil nucleus had too many leaves, and those with 5 leaves> 5% or 6 leaves appeared.

3. The bone marrow showed typical giant and juvenile changes without other pathological hematopoiesis.

4. Serum folate level decreased <6.81nmol / L, erythrocyte folic acid level <227nmol / L, vitamin B ₁₂ level decreased <75 pmol/L.

5. Experimental treatment is effective.

Megaloblastic anemia treatment

General treatment

Treat underlying diseases and remove the cause. Strengthen nutrition education to correct partial eclipse and bad cooking habits.

2. Supplement Folic Acid or Vitamin B ₁₂

(1) Folic acid lacks oral folic acid. Those who cannot absorb the gastrointestinal tract can intramuscularly inject calcium tetrahydrofolate until the hemoglobin returns to normal. Maintenance treatment is generally not required.

(2) Vitamin B ₁₂ deficiency Injected vitamin B ₁₂ intramuscularly until hemoglobin returns to normal. Patients with malignant anemia or total gastric resection need maintenance treatment for life. Vitamin B ₁₂ deficiency with neurological symptoms responds differently to treatment, sometimes requiring large doses and long-term (more than six months) treatment. For patients with simple vitamin B ₁₂ deficiency, it should not be treated with folic acid alone, otherwise vitamin B ₁₂ deficiency will be aggravated, especially to be alert to the occurrence or exacerbation of neurological symptoms.

(3) Patients with severe megaloblastic anemia should be alert to the occurrence of hypokalemia after supplementary treatment. Because during the recovery of anemia, a large amount of blood potassium enters the newly generated cells, hypokalemia will suddenly occur. For elderly patients and those with cardiovascular disease and poor appetite, special attention should be paid to timely potassium supplementation.