What Is Required for a Thalassaemia Diagnosis?

Thromboplasia anemia, formerly known as thalassemia, is also a group of hereditary hemolytic anemia diseases. Anemia or pathological condition caused by lack of or insufficient synthesis of one or more globin chains in hemoglobin due to inherited genetic defects. Due to the complexity and diversity of gene defects, the type, number and clinical symptoms of globin deficiency are relatively large. They are named and classified according to the type and degree of globin deficiency.

Basic Information

nickname

Thalassemia, thalassemia

English name

thalassemia

English alias

Mediterranean anemia

Visiting department

Hematology

Common causes

Insufficient or absent synthesis of globin chains results in

Common symptoms

Anemia, progressive exacerbation of liver and spleen, jaundice, dysplasia, etc.

Etiology of globin production anemia

The molecular structure and synthesis of globin chains are determined by genes. , , and globin genes constitute the " gene family", and and globin constitute the " gene family". A normal person inherits two alpha globin genes ( / ) from both parents to synthesize sufficient -globin chains; and one parent from each parent inherits one -globin gene to synthesize sufficient -globin chains. Due to the deletion or point mutation of the globin gene, disorders of peptide synthesis lead to disease. Thalassemia is divided into 4 types: , , , and . Among them, and are more common.

1. Beta globin production anemia (beta thalassemia)

The molecular pathology of -globin-producing anemia (-thalassemia for short) is quite complicated. It is known that there are more than 100 types of -gene mutations, mainly due to point mutations in genes, and a few are gene deletions.

2. Alpha globin production disorder anemia ( thalassemia)

Most alpha globin-producing anemia (thalassemia) (alpha thalassemia for short) is caused by the deletion of the alpha globin gene, and a few are caused by point mutations in the gene. The loss of white genes is caused by a few point mutations.

Clinical manifestations of globin production anemia

According to the severity of the disease, it is divided into the following 3 types.

1. heavy

A few days after birth, anemia, hepato-splenomegaly, progressive increase, jaundice, and dysplasia. Its special manifestations are: large head, widened eyes, saddle nose, protruding forehead, and protruding cheeks. Its typical manifestations are Gluteal head, long bones can fracture. Bone changes are caused by hyperfunction of bone marrow hematopoiesis, widening of bone marrow cavity, and thinning of cortex. A few patients have a thoracic mass between the ribs and the spine. Cholelithiasis and lower extremity ulcers are also seen.

2.Intermediate type

Mild to moderate anemia, most patients can survive to adulthood.

3. Lightweight

Mild anemia or asymptoms are usually found during a family history survey.

Globin production disorder anemia test

1. Beta globin production disorder anemia (thalassemia)

(1) The heavy peripheral blood is small cell hypochromic anemia, the size of red blood cells is different, the central superficial staining area is enlarged, and irregular, target-shaped, fragmented red blood cells and nucleated red blood cells, stippled red blood cells, polychromatic red blood cells, Howe Zhou's body, etc .; reticulocytes are normal or increased. Bone marrow showed obvious hyperplasia of red blood cell system, with middle and late red blood cells being the majority. The changes of mature red blood cells were the same as those of peripheral blood. Erythrocyte osmotic fragility was significantly reduced. The HbF content increased significantly, mostly> 0.40, which is an important basis for the diagnosis of severe thalassemia. The skull X-ray film showed that the inner and outer plates of the skull were thinned, the barriers were widened, and vertical short hair-like spurs appeared between the cortical bones.

(2) Mild mature red blood cells have slight morphological changes, red blood cell penetration is more or less normal, and hemoglobin electrophoresis shows increased HbA2 content (0.035 0.060), which is the characteristic of this type. HbF content is normal.

(3) Intermediate type Changes in peripheral blood and bone marrow, such as severe, reduced red blood cell osmotic fragility, HbF content of 0.40 to 0.80, normal or increased HbA2 content.

2. Alpha globin production disorder anemia (thalassemia)

(1) The morphology of resting red blood cells is normal. The content of Hb Bart's in umbilical cord blood at birth is 0.01 to 0.02, but it disappears after 3 months.

(2) Mild changes in morphology of red blood cells, such as unequal size, central staining, and abnormal shapes; reduced red brittle cell osmotic fragility; positive denatured globin bodies; normal or slightly lower levels of HbA2 and HbF. The Hb Bart's content in the umbilical cord blood of the children was 0.034 to 0.140, which completely disappeared at 6 months after birth.

(3) Intermediate type The changes of peripheral blood and bone marrow are similar to that of severe thalassemia; the erythrocyte fragility is reduced; the denatured globin body is positive; the content of HbA2 and HbF is normal. At birth, the blood contains about 0.25Hb Bart's and a small amount of HbH; with age, HbH gradually replaces HbBart's, and its content is 0.024 to 0.44. Inclusion body formation test was positive.

(4) Severe changes in the morphology of mature peripheral red blood cells such as severe thalassemia, nucleated red blood cell count and reticulocyte count increased significantly. Hemoglobin is almost all Hb Bart's, or there is a small amount of HbH at the same time, without HbA, HbA2 and HbF.

Diagnosis of globin production anemia

Based on clinical characteristics and laboratory tests, combined with a positive family history, a diagnosis can generally be made. Genetic diagnosis can be made when conditions permit.

The complex caused by rare types and various types of overlap is very complicated, and the clinical manifestations are different. It is impossible to diagnose based on clinical characteristics and routine laboratory hematology tests. And due to differences in gene regulation levels, patients with the same genetic mutation type may not necessarily have the same clinical manifestations. Hemoglobin electrophoresis is a necessary condition for the diagnosis of this disease, but the hematological examination after blood transfusion treatment will be different from the actual results. So genetics and molecular biology tests can make the final diagnosis. Genetic tests can identify homozygotes, heterozygotes, and double heterozygotes.

Differential diagnosis of globin production anemia

It should be distinguished from diseases such as iron deficiency anemia, infectious hepatitis or cirrhosis.

Treatment of globin production anemia

No special treatment is required for mild thalassemia. Intermediate and severe thalassaemia should be treated with one or more of the following methods. Blood transfusion and iron removal are still one of the important treatments.

General treatment

Pay attention to rest and nutrition, and actively prevent infection. Properly supplement folic acid and vitamin B ₁₂ .

2. Red blood cell transfusion

Blood transfusion is the main measure for the treatment of this disease. It is best to inject red blood cells to avoid transfusion reactions. The small infusion method is only suitable for intermediate and thalassaemias, and is not recommended for heavy thalassaemias. For severe beta thalassemia, medium and high blood transfusions should be given from the early stage in order to make the child's growth and development close to normal and prevent bone disease. The method is: repeatedly infused concentrated red blood cells, so that the hemoglobin content of the child reaches 120 to 150 g / L; and then infused concentrated red blood cells 10 to 15 ml / kg every 2 to 4 weeks to maintain the hemoglobin content at 90 to 105 g / L the above. However, this method is prone to cause hemosiderin-containing disease, so iron chelator should be given at the same time.

3.Iron chelator

Deferoxamine is commonly used to increase the excretion of iron from urine and feces, but it cannot prevent the absorption of iron from the gastrointestinal tract. Iron load assessment is usually performed after a regular infusion of red blood cells for one year or 10 to 20 units. If iron is overloaded, iron chelator is started. Deferoxamine, continuous subcutaneous injection once a night for 12 hours, or by intravenous drip in isotonic glucose solution for 8-12 hours; 5-7 days per week, long-term application. Or add slowly to the red blood cell suspension. Deferoxamine has few side effects, occasional allergic reactions, and long-term horn coupling can cause cataracts and long bone development disorders. Excessive doses can cause vision and hearing loss. The combined use of vitamin C and a chelating agent can enhance the effect of deferoxamine to excrete iron from the urine.

4. Splenectomy

Splenectomy has a good effect on hemoglobin H disease and intermediate -thalassemia, but has a poor effect on severe -thalassemia. Splenectomy can cause weakened immune function, and should be performed after 5 to 6 years of age and the indications must be strictly controlled.

5. Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation is currently the method that can cure severe beta thalassemia. HLA-matched hematopoietic stem cell donors should be the first choice for the treatment of severe beta thalassemia.

6. Gene activation therapy

The use of chemical drugs can increase the expression of gene or decrease the expression of gene to improve the symptoms of thalassemia. The drugs that have been used in clinical medicine are hydroxy (urea) urea, 5-azacytidine (5-AZC), arabinose Cytidine, malilan, isoniazid, etc. are currently under study.

Prevention of globin production anemia

In general, if two patients with the same type of thalassemia are combined, there is an opportunity to give birth to a patient with severe anemia. In order to prevent this disease effectively, blood needs to be drawn for peptide chain testing and genetic analysis. If it is confirmed that they and the spouse are both -type very mild or mild thalassemia patients, their children will have a quarter of a chance to be completely normal and a half Of them have a chance to become mildly anemic, and one in four have a chance to become moderately or severely anemic. In view of the lack of a cure for this disease, and the clinical prognosis is severe, the prognosis is poor. Therefore, doctors should make medical recommendations to patients with a positive family history or patients to conduct pre-marital examinations and prenatal genetic diagnosis of fetuses to avoid the occurrence of next-generation children.