Sickle Cell Anemia

(Hemoglobin S’s disease)

The sickle cell anemia (a hemoglobinopathy; hemoglobinopathies) is a chronic hemolytic anemia, which occurs almost exclusively in dark-skinned people and is caused by the homozygous inheritance of hemoglobin S. Sickle cell shaped red blood cells clog the capillaries and thus lead to a Organischämie. (Editor’s note:. In the course of the disease, a functional asplenia developed) Often acute pain develop (crises). Infections, bone marrow aplasia, and lung involvement (acute chest syndrome) may be acute and fatal. A normocytic hemolytic anemia is characteristic. The diagnosis is made by hemoglobin electrophoresis. Crises are treated with analgesics and supportive measures. Occasionally transfusions are necessary. Vaccination against bacterial infections, prophylactic antibiotics and aggressive treatment of infections prolong survival. Hydroxyurea can reduce the incidence of sickle cell crises.

The sickle cell anemia (a hemoglobinopathy; hemoglobinopathies) is a chronic hemolytic anemia, which occurs almost exclusively in dark-skinned people and is caused by the homozygous inheritance of hemoglobin S. Sickle cell shaped red blood cells clog the capillaries and thus lead to a Organischämie. (Editor’s note:. In the course of the disease, a functional asplenia developed) Often acute pain develop (crises). Infections, bone marrow aplasia, and lung involvement (acute chest syndrome) may be acute and fatal. A normocytic hemolytic anemia is characteristic. The diagnosis is made by hemoglobin electrophoresis. Crises are treated with analgesics and supportive measures. Occasionally transfusions are necessary. Vaccination against bacterial infections, prophylactic antibiotics and aggressive treatment of infections prolong survival. Hydroxyurea can reduce the incidence of sickle cell crises. Hemoglobinopathies hemoglobin molecules consist of polypeptide chains whose chemical structure is genetically determined. The normal hemoglobin molecule (hemoglobin A) of the adult consists of 2 pairs of a chain, which are designated as ? and ?. In addition, the normal blood also contains ? 2.5% hemoglobin A2 (consisting of ?- and ? chains). Fetal hemoglobin (hemoglobin F, which has in place of ?-chains over ?-chains) increases particularly in the first months of life, gradually decreases until it is in the adult only <2% of the total hemoglobin constitutes (hemoglobinopathies in pregnancy). The hemoglobin F concentration increases in various diseases of hemoglobin synthesis, as well as aplastic and myeloproliferative conditions. Some hemoglobinopathies result in anemias that hard to be weak in homozygotes with heterozygotes. Occasionally, patients heterozygous for two of these changes and have a anemia, having the characteristics of both diseases. Various hemoglobin molecules are distinguished by their migration in electrophoresis and in the alphabetical order of their discovery (z. B. A, B, C) named. Exception is the first discovered pathological sickle cell hemoglobin, which was called hemoglobin S. Structurally different hemoglobins at the same electrophoretic migration rate are named after the city or to the place of their discovery (z. B. Hb S Memphis, Hb C Harlem). The standard description of the hemoglobin composition of a patient first performs the hemoglobin with the highest concentration on (z. B. AS in sickle cell properties). In the US, often anemia occur that are caused by defective synthesis of hemoglobin S or hemoglobin C and thalassemia. The immigration of Southeast Asians has also resulted in an accumulation of hemoglobin E variants. Homozygous (approximately 0.3% of dark-skinned US population) have a sickle cell anemia, heterozygotes (8-13% of dark-skinned) are typically not anemic. Pathophysiology When hemoglobin S the glutamic acid is replaced at the 6th amino acids instead of the ?-chain with valine. Oxygenated hemoglobin S is less soluble than oxygenated hemoglobin A and therefore results in the formation of a semisolid gel at locations with low oxygen partial pressure (PO2) causes the deformation of erythrocytes to sickle cells. Deformed, inflexible red blood cells adhere to the vascular endothelium and plug small arterioles and capillaries, leading to a heart attack. The blockage of venous predisposed to the formation of thromboses. Because sickle cell are fragile that mechanical trauma to the circulation leads to haemolysis. Chronic compensatory hyperactivity of the bone marrow caused bone deformities. Acute exacerbations Acute exacerbations (crises) occur intermittently and often for no known reason. In some cases seem fever, viral infections trigger or local trauma a sickle cell crisis. The most common type is the painful crisis caused by ischemia and infarction, typically the bones, but also the spleen, lungs and kidneys. Aplastic crises arise when erythropoiesis in the bone marrow is decreased due to an acute, in particular viral infection. This may lead to acute PRCA. Acute chest syndrome is caused by microvascular occlusion in the lungs and, with mortality rates of up to 10% a frequent cause of death. However, it occurs in all age groups, most often in children. Recurrent episodes increase the risk of chronic pulmonary hypertension. In children acute sequestration of sickle cell can occur in the spleen, which increases the anemia. Priapism, a serious complication that can lead to erectile dysfunction, occurs most often in young men auf.Komplikationen The long-term effects include growth and developmental disorders. Chronic Milzschaden increases the susceptibility to infection, particularly pneumococcal and Salmonella infections (including osteomyelitis by salmonella). These infections are particularly common in early childhood and may extend rapidly fatal. Other consequences may be ischemic stroke, vasculitis of the central nervous system, avascular necrosis, renal impairment, renal failure, heart failure and pulmonary fibrosis. Symptoms and signs Most symptoms occur only in homozygous patients and are a result of anemia and venous occlusions that lead to tissue ischemia and infarction. Anemia is usually difficult, but pronounced differently from patient to patient. Often have a slight jaundice and pallor. The patients are mostly underdeveloped and often have a relatively short torso with long limbs and a tower skull. In children is often found hepatosplenomegaly. In adults, however, the spleen is usually very small because of repeated infarctions and subsequent fibrosis (Autosplenektomie). Cardiomegaly and systolic Ejektionsgeräusche are common. Cholelithiasis and chronic punched ulcers in the ankle are common. Painful crises cause severe pain in the long bones (eg. As pretibial pain), hands and feet (z. B. Hand-foot syndrome) and joints. By Hemarthrosis or avascular necrosis of the femoral head may cause joint pain. It can develop severe abdominal pain (with or without nausea). If these are caused by the formation of sickle cells themselves, usually occur concomitantly on back pain and joint pain. Characteristic of the acute chest syndrome is the sudden onset of fever, chest pain and pulmonary infiltrates. The start infiltrates into the lower lung sections and are present on both sides in one third of cases. They may be accompanied by a pleural effusion. Bacterial pneumonia can follow. It can develop a hypoxia quickly, what breathlessness result has. Heterozygous patients In heterozygous patients (hemoglobin AS) hemolysis, painful sickle cell crises or thrombotic complications usually do not occur, but may under hypoxic conditions (eg. As staying in high altitude, with sudden loss of pressure in airplanes) develop. However, rhabdomyolysis, and sudden cardiac death may occur during persistent, intense physical exertion. Often found a decreased ability of urine concentration (Hypostenurie). A unilateral hematuria, which occurs about unknown mechanisms and usually affects the left kidney can occur, but is self-limiting. It may typical papillary renal occur, but they are less common than in homozygous patients. Diagnostic DNA test (prenatal) Peripheral blood smear examination of solubility Hemoglobin (or thin-layer isoelectric focusing) The type of test to be carried out depends on the age of the patient. DNA testing can be used in prenatal diagnosis or confirmation of diagnosis of sickle cell disease genotype. The screening of newborns using hemoglobin electrophoresis is available in most US states. Screening and diagnosis in children and adults include examination of the peripheral blood smear, the Hämoglobinlöslichkeit and hemoglobin electrophoresis. Prenatal diagnosis The sensitivity of prenatal diagnosis was significantly increased by the availability of the PCR technique. It is recommended for families with an increased risk for sickle cell anemia (z. B. couples with anemia in their own history or family history or with an assumed ethnic background). DNA samples can chorionic villus sampling in the 8th-10th Week of pregnancy be won. The amniotic fluid may also be in the 14th-16th Week will be tested. The diagnosis is important for genetic Beratung.Neugeborenenscreening A general test is often part of the newborn screening. To distinguish between hemoglobin F, S, A and C, a hemoglobin electrophoresis on cellulose acetate or acid Citratagar, a thin layer isoelectric focusing or a hemoglobin fractionation by high performance liquid chromatography (HPLC) is recommended. To confirm the test at the age of 3-6 months should be repeated. The solubility test for hemoglobin S in the first months of life unzuverlässig.Screening and diagnosis in children and adults patients with sickle cell disease have a family history should by peripheral blood smears, solubility test for hemoglobin and hemoglobin electrophoresis are investigated. , Patients with symptoms or clinical signs suggestive of the disease (eg. As growth retardation, acute and unexplained bone pain, aseptic femoral head necrosis, unexplained hematuria), and dark-skinned patients with normozytärer anemia (especially in case of hemolysis) to a hemolytic anemia be examined (autoimmune hemolytic anemia). In addition, a hemoglobin electrophoresis and examination of red blood cells to the sickle cell phenomenon should be made. In sickle cell disease, the red blood cell count is usually 2-3 Mio./?l with correspondingly reduced hemoglobin. The cells are normocytic (a microcytosis indicates a concomitantly present ?-thalassemia out). Nucleated erythrocytes are often in the peripheral blood before and reticulocytosis of ? 10% is common. Dried blood films often exhibit sickle cell (sickle-shaped, often with elongated or pointed ends). Sickle cell with permission of the publisher. From Tefferi A., Li C. In Atlas of Clinical Hematology. Edited by J. O. Armitage. Philadelphia, Current Medicine, 2004. var model = {thumbnailUrl: '/-/media/manual/professional/images/sickle_cells_high_de.jpg?la=de&thn=0&mw=350' imageUrl: '/ - / media / manual / professional / images / sickle_cells_high_de.jpg lang = en & thn = 0 ', title:'? ', description:' sickle cell 'credits' with permission of the publisher. From Tefferi A., Li C. In Atlas of Clinical Hematology. Edited by J. O. Armitage. Philadelphia, Current Medicine, 2004. 'hideCredits: false, hideTitle: false, hideFigure: false, hideDescription: true}; var panel = $ (MManual.utils.getCurrentScript ()) Closest ( 'image-element-panel.'). ko.applyBindings (model, panel.get (0)); The homozygous state is separated in the electrophoresis, by the detection of hemoglobin S with a variable amount of hemoglobin F of other hemoglobinopathies, showing a sickle cell phenomenon. In heterozygotes a preponderance of hemoglobin A with respect to hemoglobin S. The hemoglobin S has to be distinguished from other hemoglobins with similar electrophoretic properties through the detection of pathognomonic erythrocyte morphology seen in the electrophoresis. For diagnosing a bone marrow examination is necessary. Is it performed to differentiate from other types of anemia, this shows hyperplasia with predominance of Normoblasts. During severe infections or sickle cell crises and aplasia may occur. The erythrocyte sedimentation rate (ESR), to the exclusion of other diseases (eg. B. juvenile rheumatoid arthritis, which leads to hand and foot pain) is determined, shows low values. Among the accompanying radiologically detectable skeletal changes include the expansion of Diploeräume of the skull and the image of a brush skull due to Trabekelveränderungen in Diploeräumen. The long bones frequently show cortical narrowing, irregular densities and signs of new bone formation in the medullary canal. In an unexplained hematuria should be considered a sickle cell disease, even if the patient such previously suspected wurde.Diagnostik in exacerbations in patients with a known sickle cell disease and an acute exacerbation of pain, fever or other symptoms of infection should aplastic crisis contemplated and made a blood count and reticulocyte counts are determined. A reticulocyte count <1% is an indication of an aplastic crisis, especially if the hemoglobin level falls below the normal value for the patient. During a painful crisis without aplasia of the white blood cell count often increases with a left shift (especially during a bacterial infection). Platelet counts are usually increased, the serum bilirubin, z. B. 2-4 mg / dl (34-68 .mu.mol / l). In urine urobilinogen may be detectable. Chest pain or dyspnea indicate an acute chest syndrome or pulmonary embolism. In this case, an X-ray of the chest and pulse oximetry are necessary. Hypoxemia or parenchymal infiltrates on chest X-ray image point to an acute chest syndrome or pneumonia, hypoxemia without pulmonary infiltrates to a pulmonary embolism. In patients with fever infection or acute chest syndrome in should be considered. It should be collected blood cultures, a radiograph of the chest and other appropriate tests will be done. Prognosis The life expectancy of homozygotes is constantly improving and is currently at> 50 years. Some common causes of death include acute chest syndrome, recurrent infections, pulmonary embolism, infarction of vital organs and kidney failure. Broad-spectrum antibiotic treatment (at infection) analgesics and i.v. Hydration (with vaso-occlusive painful crisis) Sometimes transfusions vaccinations, folic acid substitution and hydroxyurea (to maintain health) The therapy includes regular measures to maintain the health and the specific treatment of complications occurring. Complications are treated supportive. A drug which effectively prevents the sickling in vivo, is not available. Splenectomy has no therapeutic value. A stem cell transplantation is curative in a small number of patients, but with a 5 to 10% which is why it is not done anywhere cent mortality rate connected. Gene therapy offers hope for a cure, but it is still in the development phase. Hospitalization is indicated when the suspicion of a heavy (local or systemic) infection, aplastic crisis or acute chest syndrome consists. Indications for hospitalization are often uncontrollable pain or the need for transfusions. Fever alone should not be a reason for hospitalization. However, patients who appear very ill and have a temperature> 38 ° C should be included so that cultures of different places removed and antibiotics iv can be given. Antibiotics patients in whom a severe bacterial infection or acute chest syndrome is suspected need immediately a Breitspektrumantibiotikum.Analgetika painful sickle cell crises with generous administration of analgesics, opioids commonly treated. Morphine iv (Continuous or bolus) is effective and safe; Meperidine should be avoided. Although dehydration promotes sickling and can trigger a crisis, it is unclear whether an intensive hydration is helpful during a crisis. Nevertheless, the maintenance of normal intravenous volume is an essential part of therapy. During a crisis, pain and fever for up to 5 days can anhalten.Transfusion A transfusion is performed in numerous situations where their effectiveness has not been proven. To prevent recurrence of cerebral thrombosis, regular transfusion, however, especially in children, indexed. Transfusions are performed when the hemoglobin drops below 5 g / dl. Specific indications include acute splenic sequestration, aplastic crises, cardiopulmonary symptoms or clinical signs (eg. As high-output heart failure, hypoxemia with PO2 values ??<65 mmHg) and the preoperative use, priapism and life-threatening events supported by improving O2 supply benefit (sepsis z. B., severe infection, acute chest syndrome, stroke, acute Organischämie). The transfusion is not helpful during an uncomplicated painful crisis. Nevertheless, by the sequence of short consecutive painful crises can be interrupted occasionally. Also during pregnancy transfusions may be necessary. Partial exchange transfusions are over the simple transfusions usually preferably used, especially when transfusions or when multiple transfusions are regularly required. It can be done with modern Apheresegeräten. If the initial hemoglobin value is low (<7 g / dl), this method can not be started before the first transfusion of red blood cells. Partial exchange transfusions minimize the iron accumulation and Hyperviskosität.Erhaltung health in the long-term treatment following measures have mortality, especially in children, reduced: vaccination against pneumococcal, Haemophilus influenzae, influenza (inactive inactive) and meningococcal Early detection and treatment of serious bacterial infections prophylactically, including continuous prophylaxis with penicillin aged 4 months to 6 years administration of hydroxyurea and folic acid substitution, the additional administration of folic acid is usual antibiotics (1 mg po once daily). Hydroxyurea leads to an increase in hemoglobin F and thereby to a reduction of sickling. This painful crises are reduced by about 50% and reduces the risk of acute chest syndrome and transfusion requirements. The dose of hydroxyurea is variable and should be adapted to the increasing hemoglobin F value. Even more effective in certain patients hydroxyurea is possibly in combination with erythropoietin (z. B. 40,000 to 60,000 units / week). However, hydroxyurea is a leukemogenic and causes neutropenia and thrombocytopenia. It is also a teratogen and should not be given to women of childbearing age. Transcranial Doppler flow studies in children can help predict the risk of stroke, and many experts recommend annual screenings for children aged 2 to 16 years. Children at high risk seem to benefit from prophylactic, chronic, partial exchange transfusions that keep Hb <30% of the total Hb; iron overload is common and has to be checked and treated. The Erythropoetingabe in anemia patients outside chemotherapy was brought (myocardial infarction z. B.) associated with a higher incidence of venous thromboembolic events and cardiopulmonary complications. It is usually in patients with sickle cell disease is not helpful, except perhaps when it is used in combination with hydroxyurea. Important Points patients who are homozygous for HbS, have something to fragile abnormal ?-chain, relatively inflexible erythrocytes leads, can clog the capillaries, which in turn causes tissue infarction, and are prone to hemolysis, which causes anemia. Patients have different acute exacerbations, including painful crisis Sequestrierungskrise, aplastic crisis and acute chest syndrome. Among the long-term consequences include poor growth, high blood pressure, chronic kidney disease, stroke, aseptic necrosis and increased risk of infection. The diagnosis is made on the Nutzing of hemoglobin electrophoresis. In acute crises opioid analgesics are given to pain; Moreover, checking for deterioration of anemia occurs (indicating a aplastic or Sequestrierungskrise) and signs of acute chest syndrome or an infection, as well as the restoration of normal intravascular volume with 0.9% saline and then subjected to administration of maintenance fluids. Infections be prevented through vaccinations and prophylactic antibiotics; painful crises and the risk of acute chest syndrome carried out by the administration of hydroxyurea.

Leave a Reply