What Is Involved in the Management of Sickle Cell Anemia?

Sickle cell anemia is an autosomal dominant inherited hemoglobin (Hb) disease. The glutamic acid at position 6 of the -peptide chain was replaced by valine to form sickle hemoglobin (HbS), which replaced normal Hb (HbA). The clinical manifestations are chronic hemolytic anemia, susceptibility to infection and recurrent pain crisis leading to chronic ischemia leading to organ and tissue damage. At present, there is no clear change in the genetic composition of the affected individual, so the treatment of the cause is not meaningful. The purpose of treatment is to prevent hypoxia, dehydration and infection. Check for Plasmodium and antimalarial treatments during fever to relieve symptoms and reduce complications of organ damage; promote hematopoietic and prolong life.

Wang Jing	(Deputy Chief Physician)	Institute of Hematology, Peking University People's Hospital
Jiang Hao	(Deputy Chief Physician)	Institute of Hematology, Peking University People's Hospital
Huang Xiaojun	(Chief physician)	Institute of Hematology, Peking University People's Hospital

Western Medicine Name: Sickle cell anemia

Affiliated Department: Internal Medicine-Hematology
Contagious: Non-contagious

Introduction to sickle cell anemia

Sickle cell anemia is an autosomal dominant inherited hemoglobin (Hb) disease. The glutamic acid at position 6 of the -peptide chain was replaced by valine to form sickle hemoglobin (HbS), which replaced normal Hb (HbA). The clinical manifestations are chronic hemolytic anemia, susceptibility to infection and recurrent pain crisis leading to chronic ischemia leading to organ and tissue damage. It is also a disease that seriously endangers the health of the mother and child, which can cause a fetal mortality rate of 5% and a maternal mortality rate of 4.62% ^[1] .

Causes of sickle cell anemia

It is an autosomal dominant inherited hemoglobin disease. The most common is that both parents have an abnormal gene called homozygous SS. The SS type is completely free of normal HbA. More than 80% are replaced by HbS. The prognosis of the SS type is serious, only 14% live to adulthood, and more than 30 die. Before the age. Heterozygous type, that is, normal HbA mixed with abnormal HbS is also called AS. In Africa, 35% of patients are of the AS-type gene; those with very different changes can survive to adulthood, and severe cases can have recurrent crisis attacks ^[2] .

Pathogenesis of Sickle Cell Anemia

Normal adult hemoglobin is a tetramer composed of two alpha chains and two beta chains, and the alpha and beta chains are respectively connected by 141 and 146 amino acid sequences. In patients with sickle cell anemia, because the glutamic acid at the 6th position of the beta chain is replaced by valine, abnormal hemoglobin S (HbS) is formed, replacing normal hemoglobin (HbA). When the partial oxygen pressure drops, HbS The intermolecular interaction becomes a helical polymer with very low solubility, which distorts red blood cells into sickle cells (sickness). Many factors such as the concentration of HbS, the degree of deoxygenation, the degree of acidosis, and the degree of dehydration of red blood cells in red blood cells are related to the sickness of red blood cells ^[3] .

Pathophysiology of Sickle Cell Anemia

The initial sickle of red blood cells is reversible. Oxygen can reverse the sickle process. But when the sickle has severely damaged the red blood cell membrane, the sickle becomes irreversible. Even if the cells are placed under aerobic conditions, the red blood cells remain sickle-shaped. The sickled red blood cells are stiff and deformable, and can be hemolyzed by the destruction of vascular mechanisms and engulfing by the mononuclear macrophage system. Sickled red blood cells can also increase blood viscosity, slow blood flow, and poor deformability, which can easily block capillaries and cause local hypoxia and inflammatory reactions leading to pain crises in the corresponding parts, which mostly occur in muscles, bones, joints of limbs, Chest and abdomen, especially joints and chest and abdomen are common ^[4] .

Clinical manifestations of sickle cell anemia

In addition to anemia, clinical features also present a periodic pain crisis; and visceral hypoxia caused by various causes causes more red blood cell sickle to cause severe complications such as multiple pulmonary, kidney, liver, and cerebral embolism. In addition to the patients with the corresponding symptoms and signs, hematological, immunological and hematological changes will also occur. In addition, it can still affect the development of the nervous system and cause mental retardation. The early pathological changes of sickle cell anemia are sickle red blood cells that damage the spleen vasculature, making patients vulnerable to infection, especially pneumococcal sepsis and chlamydia pneumonia. Acute chest syndrome appears clinically, and the clinical features are fever, cough, dyspnea, chest pain, There are lung mutations or infiltrations in the line; slow onset of antibiotics is also the main cause of death in all age groups ^[5] .

Hemolysis causes increased bilirubin and jaundice, liver, and gallstones. If a large amount of blood stays in the liver and spleen, progressive hepatosplenomegaly will occur and hypovolemic shock will occur, which is also called retention crisis or relapse syndrome.

Hand and foot joint swelling and congestion due to microvascular occlusion caused by local tissue hypoxia and inflammatory response is called hand and foot syndrome. 50% of children within 2 years of age have hand-foot syndrome.

Diagnosis and differential diagnosis of sickle cell anemia

Diagnosis: Sickle cell anemia diagnostic criteria: 1. Clinical manifestations (jaundice, anemia, hepatosplenomegaly, bone and joint, chest and abdominal pain, etc.); 2. sickness of red blood cells; 3. genetic history; 4. incidence in ethnic regions; 5. Hb analysis.

Because of clinical manifestations of limb, joint pain, anemia jaundice, chest and abdomen pain, etc., it should be distinguished from rheumatic pain, osteomyelitis, congenital syphilis and so on. Because African patients have dark skin and pale faces, it is not easy to be found.The authors realized that anemia can only be detected by examining the color of the eye conjunctiva, oral mucosa, and nail bed; and its clinical and X-ray manifestations are complex and changeable, and it is easy to misdiagnose as malnutrition anemia, Rheumatic fever, hepatitis, thalassemia, etc. Therefore, in the epidemic area or high-incidence group, one of the following should be related to the possibility of this disease: 1. Children with stunted growth and anemia; 2. Anemia with family history; 3. Repeated hand and foot swelling and pain in children, anti-rheumatic treatment Poor results; 4. Unexplained lung infection and hepatosplenomegaly. Diagnostic methods include sickle test and Hb electrophoresis, globin fingerprint analysis, and amino acid analysis. Among them, the sickle test has low cost, simple method, reliable results and easy popularization ^[6] .

Sickle cell anemia disease treatment

At present, there is no clear change in the genetic composition of the affected individuals, so the treatment of the cause is not meaningful. The purpose of treatment is to prevent hypoxia, dehydration and infection. Check for Plasmodium and antimalarial treatments during fever to relieve symptoms, reduce complications of organ damage, promote hematopoiesis and prolong life.

In severe cases, hydroxyurea can reduce the number of pain crises and blood transfusions, and it can also reduce the frequency of chest syndrome. The disease is mainly due to hypoxia, the sickness of red blood cells sickle capillaries and cause pain crisis, it is appropriate to use alternative treatments and vasodilator drugs. Folic acid supplementation can reduce elevated cysteine levels and improve vascular endothelial function. Bone marrow transplantation and fetal liver hematopoietic stem cell transplantation are also performed to save patients and improve quality of life. The indirect flow blood cell separator is used to separate the patient's red blood cells and the donor's de-glycerolized red blood cells are used to obtain better results. There are also suggestions that partial blood exchange and intravenous drip of 5% glucose to reduce blood viscosity. Low-dose coumarin treatment can reduce the occurrence of prethrombotic state in patients.

Prognosis of sickle cell anemia

Patients with homozygotes (ie, sickle cell anemia) have higher HbS concentrations in red blood cells, significantly reduced affinity for oxygen, accelerated release of oxygen, and poor prognosis. Only 14% of patients survive to adulthood and die before the age of 30. Patients with HbS heterozygotes (ie, sickle cell traits), due to the low concentration of HbS in red blood cells, generally do not develop sickness or anemia except under hypoxic conditions. They are clinically asymptomatic or have occasional hematuria and spleen infarction.

Prevention of sickle cell anemia

The genetic characteristics of this disease provide a way to prevent the birth of children with genetic diseases and avoid marriage between carriers. Therefore, it is safe and reliable to check pregnant women's amniotic fluid cell nuclear enzymes and analyze DNA fragments to determine whether the fetus is sick for those whose parents are HbAS. If HbSS or HbAS is suggested, necessary measures can be taken to improve the quality of the population.