hereditary spherocytosis
Introduction
Introduction to hereditary spherocytosis Hereditary spherocytosis is a hereditary hemolytic anemia that has two genetic modes, dominant and recessive. Complications such as hemolytic crisis, cholelithiasis, gout, stubborn ankle ulcers or erythematous ulcers of the lower extremities may occur. basic knowledge Sickness ratio: 0.0001% Susceptible people: no special people Mode of infection: non-infectious Complications: anemia, recurrent ulcer, gout, cardiomyopathy
Cause
Causes of hereditary spherocytosis
Cause of disease
The disease is caused by mutations in the erythrocyte membrane protein that cause erythrocyte membrane defects, most of which are autosomal dominant, and a few are autosomal recessive. Normal erythrocyte membranes are composed of bilayer lipids and membrane proteins. Mutations in genes cause defects in a variety of membrane proteins, primarily membrane cytoskeletal proteins, either alone or in combination.
Pathophysiology
Pathophysiological changes in red blood cells:
1 The erythrocyte membrane bilayer lipid is unstable and lost, the red blood cell surface area is reduced, the surface area to volume ratio is decreased, and the red blood cells become small spherical.
2 erythrocyte membrane cation permeability increased, sodium and water enter the intracellular and potassium ooze out of the extracellular, in order to maintain the balance of calcium and ions inside and outside the red blood cell, the sodium pump strengthens the ATP deficiency, the calcium-ATPase is inhibited, and the cell calcium ion concentration rises. High and deposited on the erythrocyte membrane.
3 erythrocyte membrane protein phosphorylation function decreased, peroxidase increased, membrane-bound hemoglobin increased, the above changes can make the erythrocyte membrane deformation performance and flexibility can be weakened, a small amount of water into the cell is easy to swell and hemolysis, red blood cells through the spleen It is easily destroyed and dissolved, and extravascular hemolysis occurs.
Prevention
Hereditary spherocytosis prevention
There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease.
Complication
Hereditary spherocytosis complications Complications, anemia, recurrent ulcer, gout, cardiomyopathy
1. Hematopoietic crisis: Most HSs may have various hematopoietic crisis in their disease process, aggravating anemia.
(1) Hemolytic crisis: the most common, mild symptoms, often no significant clinical significance, the course of the disease is self-limiting, generally secondary to a variety of infections caused by mononuclear macrophage system function transiently enhanced.
(2) Aplastic anemia crisis: rare, severe symptoms, life-threatening, often requiring blood transfusion, clinical features of low bone marrow erythroid hyperplasia, reticulocyte count decreased, the crisis is generally caused by parvovirus B19 infection, parvovirus B19 can invade erythroid progenitor cells and inhibit its proliferation and differentiation. The signs of parvovirus B19 infection are influenza-like syndrome and cheek flushing syndrome (expressed as red maculopapular rash on the face, trunk and limbs), and parvovirus B19 is contagious. And the harm to the fetus, therefore, the occurrence of aplastic anemia crisis should be isolated, especially to avoid contact with pregnant women, micro-virus B19 infection can obtain continuous immunity.
(3) Giant cell anemia crisis: When the supply of folic acid in the diet is insufficient or the body's demand for folic acid is increased, such as repeated hemolysis, pregnancy, etc. without timely supplementation, megaloblastic anemia may occur.
2. Gallbladder stones: More than half of HS suffer from bilirubin gallstone disease, the highest incidence rate is 10 to 30 years old (55% to 75%). The incidence rate after 30 years old is the same as that of the general population, and the incidence of children under 10 years old The rate is less than 5% and the youngest patient is only 3 years old.
3. Others: Rare complications include recurrent lower extremity ulcers, chronic erythematous dermatitis and gout, which can be cured after splenectomy. The formation of lower extremity ulcers may be related to decreased red blood cell deformability and stasis of blood flow, and gout may occur due to cells. The conversion is accelerated. A few old young HSs can develop extramedullary hematopoietic masses, especially laryngeal masses. After splenectomy, the masses may have fatty metamorphosis, but rarely resolve. Individual patients may have spinal demyelinating disease. Mental retardation and familial cardiomyopathy, HS with neurological diseases are mainly seen in the lack of ankyrin.
Symptom
Hereditary spherocytosis symptoms Common symptoms Red blood cells, various organs, blood flow, slow hemolytic anemia, jaundice
Anemia, jaundice and splenomegaly are the most common clinical manifestations of HS patients. The three can exist at the same time, or they can occur alone. HS can occur at any age, and the clinical manifestations vary from asymptomatic to life-threatening anemia. % of HS symptoms are mild, although hemolysis, but due to bone marrow erythroid compensatory hyperplasia, generally no anemia, no or mild jaundice, no or mild splenomegaly, such patients are only conducting family investigations or due to some incentives Increased red blood cell destruction is only found, the most common cause of infection, long-lasting heavy physical activity can also aggravate hemolysis, because exercise increases spleen blood flow, about 2 / 3 of HS has mild or moderate anemia, moderate splenomegaly Large and intermittent jaundice, a small number of HS patients can develop life-threatening hemolysis, need regular blood transfusion, growth and bone development can also be affected, if the anemia is mild, generally does not cause symptoms, but other chronic hemolytic diseases, in the disease Various hematopoietic crisis such as hematopoietic arrest can occur at any stage.
Astragalus is the most common clinical manifestation in the neonatal period. 30% to 50% of adult HS can be traced back to the history of jaundice in the first week after birth. After the neonatal period, most of the jaundice is very mild and intermittent. , tired, mood swings, pregnancy, etc. can aggravate or induce jaundice.
The spleen is generally moderately swollen, and 75% to 92% of HS patients can reach the spleen during physical examination. The size of the splenomegaly has nothing to do with the severity of the disease, and the liver is generally not swollen.
Examine
Examination of hereditary spherocytosis
1. Peripheral blood: Hemoglobin and red blood cells are normal or slightly reduced, white blood cells and platelets are normal, reticulocyte counts are increased, up to 92%, the lowest is 2%, generally 5% to 20%, when aplastic anemia crisis occurs At the time, the peripheral blood three series decreased, the reticulocyte count decreased, and more than 50% of HS patients had increased MCHC. The reason was that red blood cells were in a mild dehydration state, the spleen could not be changed, MCV could be increased, normal or decreased, and MCH changes and MCV is consistent, the typical cell morphology of red blood cell morphology HS is small red blood cell volume, the loss of normal biconcave is spherical, the center of the cell is dense and lacks pale area, the cell diameter becomes shorter (6.2 ~ 7.0m) but the thickness increases (2.2 ~ 3.4m) The shape and size of spherical cells are relatively uniform. Spherical cells are only found in mature red blood cells. The morphology of nucleated red blood cells and reticulocytes is normal. The morphology of red blood cells is uneven in the whole blood, and 20% to 25% of HS lacks typical spherical cells. In heavy HS, in addition to a large number of spherical cells, blood smears can also see many spiny red blood cells, mushroom-shaped red blood cells are mainly found in zone 3 protein-deficient HS.
2. Penetration fragility test: The osmotic fragility is increased, the normal saline concentration of normal red blood cells begins to hemolysis is 0.42%~0.72%, the complete hemolysis is 0.28%~0.32%, and the concentration of HS red blood cells begins to hemolyze 0.52%~0.72%, a few 0.87%, the red blood cell osmotic fragility test is a relatively sensitive method, but 20% to 25% of patients lack typical spherical red blood cells, the osmotic fragility test is normal or slightly increased, but the incubation osmotic fragility test is almost increased, in addition, the osmotic fragility curve The shape is normal but the curve is shifted to the left or the curve is trailing.
3. Qualitative analysis of erythrocyte membrane proteins: SDS-PAGE analysis of membrane proteins, more than 80% of HS can be found abnormal (membrane protein deletion), combined with Western blot, the detection rate is higher.
4. Quantitative determination of erythrocyte membrane protein: Most HSs have one or more membrane proteins. Direct determination of erythrocyte membrane protein is the most reliable method. SDS-PAGE is often used to determine membrane proteins, but the results are not accurate enough. For the determination of ankyrin, the membrane protein content of each red blood cell is directly determined by radioimmunoassay or ELISA, and the trypsin hydrolysis method can also be used for membrane contraction protein analysis.
5 Application of molecular biology techniques: The application of modern molecular biology techniques can detect membrane protein abnormalities at the molecular level. For example, RFLP or tandem repeat number analysis (RNTR) can be used to determine the correlation between HS and a gene. Chain conformation polymorphism analysis (SSCP), polymerase chain reaction (PCR) combined with nucleotide sequencing can detect the mutation point of membrane protein gene.
6 Others: Increased serum bilirubin is mainly caused by indirect bilirubin increase, most of which is (27.4±18.8) mol/L, serum haptoglobin decreases, lactate dehydrogenase increases, Coombs test is negative, bone marrow appears erythroid cell hyperplasia There are nucleated red blood cells as high as 25% to 60%, and serum folate levels are generally reduced.
7. According to the condition, clinical manifestations, symptoms and signs, choose B-ultrasound, electrocardiogram, X-ray and other tests.
Diagnosis
Diagnosis and differentiation of hereditary spherocytosis
diagnosis
According to the clinical manifestations of anemia, jaundice, splenomegaly, spherical red blood cells increase, and the erythrocyte osmotic fragility increases to make a diagnosis. A positive family history is more helpful in confirming the diagnosis. For the small number of spherical red blood cells, it can be used as an erythrocyte osmotic fragility test and a self-hemolytic test after incubation. If it is positive, it has diagnostic significance.
Differential diagnosis
It should be noted that the red blood cell osmotic fragility can be reduced when iron is deficient. When the disease is combined with iron deficiency, the erythrocyte osmotic fragility may be normal. The autoimmune hemolysis patients have both hemolysis and spherical red blood cells, which is easy to be confused with the disease. Coombs test Positive. Adrenal cortical hormone treatment can be used to identify, light HS can be mistaken for jaundice hepatitis when there is no hemolysis, should be noted.
