Shortened red blood cell lifespan
Introduction
Introduction Heavy beta thalassemia is a homozygote of 0 or + thalassemia or a double heterozygote of 0 and + thalassemia, because -strand formation is completely or almost completely inhibited, so that the synthesis of HbA containing -chain is reduced or disappeared, and redundant The chain is combined with the chain to become HbF (a22), which significantly increases HbF. Due to the high oxygen affinity of HbF, the patient's tissue is hypoxic. Excess a-chain is deposited in the red blood cells and red blood cells, and the a-chain inclusion bodies are attached to the red blood cell membrane to become stiff, and are mostly destroyed in the bone marrow to cause "ineffective hematopoiesis". Some of the red blood cells containing inclusion bodies mature and are released into the peripheral blood, but they are easily destroyed when they pass through the microcirculation; this inclusion body also affects the permeability of the red blood cell membrane, resulting in shortened life of red blood cells.
Cause
Cause
The disease is caused by a deletion or point mutation of the globin gene. There are four kinds of peptide chains constituting globin, namely , , , chains, which are respectively encoded by their corresponding genes. Deletions or point mutations of these genes can cause synthesis disorder of various peptide chains, resulting in components of hemoglobin. change. Thalassemia is usually divided into four types: , , , and , among which and thalassemia are more common.
1. beta thalassemia
The human beta globin gene cluster is located at 11p15.5. The occurrence of beta thalassemia (referred to as beta thalassemia) is mainly due to point mutations in genes, and a few are gene deletions. Gene deletion and some point mutations can completely inhibit the production of -chain, called 0 thalassemia; some point mutations inhibit the production of -chain, which is called + thalassemia. There are more mutations in the -thalassaemia gene, and more than 100 mutation points have been discovered so far, and 28 have been found in China. There are 6 common mutations: 141-42 (-TCTT), about 45%; 2IVS-II654 (CT), about 24%; 317 (AT); about 14%; 4TATA box- 28 (A T), about 9%; 571-72 (+A), about 2%; 626 (G A), that is, HbE26, about 2%.
Heavy beta thalassemia is a homozygote of 0 or + thalassemia or a double heterozygote of 0 and + thalassemia, because -strand formation is completely or almost completely inhibited, so that the synthesis of HbA containing -chain is reduced or disappeared, and redundant The chain is combined with the chain to become HbF (a22), which significantly increases HbF. Due to the high oxygen affinity of HbF, the patient's tissue is hypoxic. Excess a-chain is deposited in the red blood cells and red blood cells, and the a-chain inclusion bodies are attached to the red blood cell membrane to become stiff, and are mostly destroyed in the bone marrow to cause "ineffective hematopoiesis". Some of the red blood cells containing inclusion bodies mature and are released into the peripheral blood, but they are easily destroyed when they pass through the microcirculation; this inclusion body also affects the permeability of the red blood cell membrane, resulting in shortened life of red blood cells. For the above reasons, the child is clinically chronic hemolytic anemia. Anemia and hypoxia stimulate the secretion of erythropoietin, which causes the bone marrow to increase hematopoiesis, thus causing bone changes. Anemia increases the absorption of iron by the intestines, and repeated blood transfusions during the treatment process cause iron to be stored in large quantities in the tissue, resulting in hemosiderosis. Light thalassemia is a heterozygous state of 0 or + thalassemia, and the synthesis of -strand is only slightly reduced, so its pathophysiological changes are extremely mild. Intermediate beta thalassemia is a double heterozygote of some + thalassemia and homozygous for some thalassemia variants, or a double heterozygous state of two different variant globin-producing anemias, the pathophysiological changes Between heavy and light.
2. alpha thalassemia
The human a globin gene cluster is located at 16Pter-p13.3. There are 2 a-bead genes in each chromosome, and a pair of chromosomes have 4 a-globin genes. Most a thalassemia (abbreviated as a thalassemia) is due to the deletion of the a-globin gene, and a few are caused by gene point mutations. If only one gene on a chromosome is missing or defective, the synthetic part of the alpha chain is inhibited, called a+ thalassemia; if two a genes on each chromosome are missing or defective, it is called a0 thalassemia.
Heavy alpha thalassemia is a homozygous state of a0 thalassemia, and its four a-globin genes are all deleted or defective, so that no a-chain is formed at all, and thus the synthesis of HhA, HbA2 and HbF containing a-chain is reduced. A large number of gamma-chain synthesis gamma 4 (HbBart's) occurs in the patient's fetal period. HbBart's affinity for oxygen is extremely high, causing tissue hypoxia and causing fetal edema syndrome. The intermediate type and alpha thalassemia are heterozygous states of 0 and a+ thalassemia, which are caused by deletion or defect of three a-globin genes. The patient can only synthesize a small amount of chain, and the excess chain is synthesized HbH (4). . HbH has a high affinity for oxygen and is an unstable hemoglobin. It is easy to denature and precipitate in red blood cells to form inclusion bodies, which causes the erythrocyte membrane to be stiff and shorten the life of red blood cells. Light alpha thalassemia is a+ homosexual homozygous or a0 thalassemia heterozygous state. It has only 2 a-globin gene deletions or defects, so there is a considerable amount of a-chain synthesis, and the pathophysiological changes are slight. The static a thalassemia is a heterozygous heterosexual state, which has only one alpha gene deletion or defect, the synthesis of the a chain is slightly reduced, and the pathophysiological changes are very slight.
Examine
an examination
Related inspection
Blood routine erythropoietin bone marrow analysis hemoglobin hemoglobin A2
According to clinical features and laboratory tests, combined with a positive family history, a diagnosis can generally be made. When there are conditions, genetic diagnosis can be made. The peripheral blood is small cell hypochromic anemia, the red blood cell size is different, the central light-stained area is enlarged, and there are abnormal shapes, target shapes, debris red blood cells and nucleated red blood cells, spotted red blood cells, polychromatic red blood cells, and Hao-Zhou body. Etc.; reticulocytes are normal or elevated. Bone marrow is markedly active in the red blood cell system, with medium and late red blood cells accounting for the majority, and mature red blood cells are the same as peripheral blood. Red blood cell osmotic fragility is significantly reduced. The HbF content is significantly increased, mostly >0.40, which is an important basis for the diagnosis of heavy thalassemia. X-ray films of the skull showed thinning of the inner and outer plates of the skull, widening of the stenosis, and vertical short-like spurs between the cortical bones.
Diagnosis
Differential diagnosis
Low red blood cells: low red blood cells are clinical manifestations of iron deficiency anemia in children.
The red blood cell distribution width is low: the red blood cell distribution width is low, which is an auxiliary indicator of the red blood cell system. Red blood cell distribution width RDW is a parameter for variability of red blood cell volume, which is obtained by blood cell analyzer. Most foods are expressed by the coefficient of variation of the measured red blood cell volume (RDW-CV), and the reference value is 11.5%-14.5%. Above normal, it is mainly used for differential diagnosis of iron deficiency anemia and thalassemia.
Red blood cell malformation: Red blood cell malformation is clinically more suggestive of glomerulonephritis. Morphological examination of urinary red blood cells is a widely used method in clinical application in the past decade. The basic principle is that glomerular-derived red blood cells are affected by mechanical damage of the glomerular basement membrane and/or intra-osseous osmotic gradient, and the morphology is often distorted. The urinary red blood cell morphology of non-glomerular hematuria is generally absent. The above changes occur and show a uniform positive shape. This can help distinguish between glomerular hematuria and non-glomerular hematuria.
